inpi-deinp/df prot. 000307-04 issn 0004-2730 ...¡ucia carneiro universidade federal de são paulo...

Abril 2009 Arquivos Brasileiros de Endocrinologia e Metabologia

Sociedade Brasileira de Endocrinologia e Metabologia

53

INPI-DEINP/DF PROT. 000307-04 ISSN 0004-2730

ENDOCRINOLOGIA & METABOLOGIA

Suplemento 2

EDITOR CHEFEEdna T. Kimura (SP)

CO-EDITORES

Sandra R. G. Ferreira (SP)

Evandro S. Portes (SP)

Magnus R. Dias da Silva (SP)

Licio A. Velloso (SP)

EDITOR aSSOCIaDO InTERnaCIOnalAntonio C. Bianco (EUA)

EDITORES aSSOCIaDOS

PRESiDEnTES DoS DEPARTAMEnToS DA SBEM

ADREnAL E HiPERTEnSão

Milena F. Caldato (PA)

DiABETES MELiTo

Saulo Cavalcanti da Silva (MG)

DiSLiPiDEMiA E ATERoSCLERoSE Maria Teresa Zanella (SP)

EnDoCRinoLoGiA BáSiCA Vânia M. Corrêa da Costa (RJ)

EnDoCRinoLoGiA FEMininA E

AnDRoLoGiA Poli Mara Spritzer (RS)

EnDoCRinoLoGiA PEDiáTRiCA Ângela M. Spinola de Castro (SP)

METABoLiSMo ÓSSEo E MinERAL

Victória Z. Cochenski Borba (PR)

nEURoEnDoCRinoLoGiA Mônica Roberto Gadelha (RJ)

oBESiDADE Marcio C. Mancini (SP)

TiREÓiDE Edna T. Kimura (SP)

REPRESEnTAnTES DAS SoCiEDADES CoLABoRADoRAS

SBD Marilia de Brito Gomes (RJ)

ABESo João Eduardo nunes Salles (SP)

SoBEMoM Francisco Bandeira (PE)

BRazIlIan aRCHIvES OF EnDOCRInOlOgy anD METaBOlISM

Arquivos Brasileiros de

EndocrinologiA& MEtABologiA

Órgão oficial de divulgação científica da SBEM – Sociedade Brasileira de Endocrinologia e Metabologia (Departamento da Associação Médica Brasileira), SBD – Sociedade Brasileira de Diabetes, aBESO – Associação Brasileira para o Estudo da Obesidade e Síndrome Metabólica e SOBEMOM – Sociedade Brasileira de Estudos do Metabolismo Ósseo e Mineral

Comissão Editorial nacional

Adriana Costa e Forti (CE)

Alexander Augusto S. Jorge (SP)

Amélio F. Godoy Matos (RJ)

Ana Claudia Latronico (SP)

Ana Luiza Silva Maia (RS)

André Fernandes Reis (SP)

Antonio Carlos Lerario (SP)

Antônio Roberto Chacra (SP)

Ayrton Custódio Moreira (SP)

Berenice B. Mendonça (SP)

Bruno Geloneze neto (SP)

Carlos Alberto Longui (SP)

Carmen C. Pazos de Moura (RJ)

Célia Regina nogueira (SP)

César L. Boguszewski (PR)

Claudio E. Kater (SP)

Denise Pires de Carvalho (RJ)

Eder Carlos R. Quintão (SP)

Fábio Fernando Lima Silva (RJ)

Francisco de Assis Rocha neves (DF)

Geraldo Medeiros neto (SP)

Gil Guerra Jr. (SP)

Gisah M. do Amaral (PR)

Hans Graf (PR)

Helena Schimid (RS)

Henrique de Lacerda Suplicy (PR)

ieda T. n. Verreschi (SP)

Jorge Luiz Gross (RS)

José Gilberto Henriques Vieira (SP)

Júlio Abucham (SP)

Laércio Joel Franco (SP)

Laura S. Ward (SP)

Lucio Vilar (PE)

Luís Eduardo P. Calliari (SP)

Luiz Armando de Marco (MG)

Luiz Augusto Casulari R. da Motta (DF)

Luiz Henrique Canani (RS)

Marcello Delano Bronstein (SP)

FUnDaDORWaldemar Berardinelli (RJ)

EDITORES E CHEFES DE REDaÇÃO*1951-1955 Waldemar Berardinelli (RJ)Thales Martins (RJ)

1957-1972 Clementino Fraga Filho (RJ)

1964-1966* Luiz Carlos Lobo (RJ)

1966-1968* Pedro Collett-Solberg (RJ)

1969-1972* João Gabriel H. Cordeiro (RJ)

1978-1982 Armando de Aguiar Pupo (SP)

1983-1990 Antônio Roberto Chacra (SP)

1991-1994 Rui M. de Barros Maciel (SP)

1995-2006 Claudio Elias Kater (SP)

2009-2010

Márcia nery (SP)

Márcio Faleiros Vendramini (SP)

Margaret Boguszewski (PR)

Margaret de Castro (SP)

Maria Honorina Cordeiro Lopes (MA)

Maria Marta Sarquis Soares (MG)

Mário José A. Saad (SP)

Mário Vaisman (RJ)

Marise Lazaretti Castro (SP)

Mauro A. Czepielewski (RS)

Mônica Gabbay (SP)

osmar Monte (SP)

Pedro Weslley S. do Rosário (MG)

Regina Célia S. Moisés (SP)

Renan Magalhães Montenegro Jr. (CE)

Ricardo M. R. Meirelles (RJ)

Rui M. de Barros Maciel (SP)

Ruth Clapauch (RJ)

Sandra Mara Ferreira Villares (SP)

Sérgio Atala Dib (SP)

Sonir Roberto R. Antonini (SP)

Tânia A. S. Bachega (SP)

Thaís Della Manna (SP)

Ubiratan Fabres Machado (SP)

Comissão Editorial internacionalCharis Eng (EUA)

Décio Eizirik (Bélgica)

Efisio Puxeddu (itália)

Fernando Cassorla (Chile)

Franco Mantero (itália)

Fredric E. Wondisford (EUA)

Gilberto Velho (França)

James A. Fagin (EUA)

John P. Bilezikian (EUA)

norisato Mitsutake (Japão)

Patrice Rodien (França)

Peter Kopp (EUA)

Indexada por Biological Abstracts, Index Medicus, Latindex, Lilacs, MedLine, SciELO, Scopus, ISI-Web of Science

Assistente editorial e financeira: Roselaine Monteiro

Rua Botucatu, 572 – conjunto 83 – 04023-062 – São Paulo, SP Tel/Fax: (11) 5575-0311 / [email protected]

Submissão on-line / Divulgação eletrônicawww.sbem.org. br • www.scielo.br/abem

ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA.

Sociedade Brasileira de Endocrinologia e Metabologia. – São Paulo, SP: Sociedade Brasileira de Endocrinologia e Metabologia, v. 5,1955-

Nove edições/ano

Continuação de: Arquivos Brasileiros de Endocrinologia (v. 1-4), 1951-1955)

Título em inglês: Brazilian Archives of Endocrinology and Metabolism

ISSN 0004-2730 (versões impressas)

ISSN 1677-9487 (versões on-line)

1. Endocrinologia – Periódicos 2. Metabolismo-Periódicos I. Sociedade Brasileira de Endocrinologia e Metabologia II. Associação Médica Brasileira.

CDU 612.43 Endocrinologia

CDU 612.015.3 Metabolismo

Apoio:

Tiragem desta edição: 4.000 exemplares Preço da Assinatura: R$ 450,00/ano – Fascículo Avulso: R$ 55,00

Rua Alvorada, 631 – Vila Olímpia – 04550-003 – São Paulo – SPTel.: (11) 3849-0099/3044-1339 [email protected] • growup-eventos.com.brAssessoria Comercial: Reginaldo Ramos

Avenida Vereador José Diniz, 3.300, 15o andar, Campo Belo 04604-006 – São Paulo, SP. Fone: 11 3093-3300 www.segmentofarma.com.br • [email protected]

Diretor-geral: Idelcio D. Patricio Diretor executivo: Jorge Rangel Gerente comercial: Rodrigo Mourão Diretor de criação: Eduardo Magno Gerente editorial: Alexandre Costa Assistente comercial: Andrea Figueiro Coordenadora editorial: Sandra Regina Santana Diretora de arte: Renata Variso Revisora: Glair Picolo Diagramação: Flávio Santana Produtor gráfico: Fabio Rangel Cód. da publicação: 8634.04.09

Arquivos Brasileiros de

EndocrinologiA & MEtABologiA

SBEM – SociEdAdE BrASilEirA dE EndocrinologiA E MEtABologiA

DIRETORIa naCIOnal Da SBEM (2009-2011)

Presidente: Ricardo M. R. MeirellesVice-Presidente: Airton Golbertsecretário executiVo: Josivan Gomes de Limasecretário Adjunto: Eduardo Pimentel Diastesoureiro GerAl: Ronaldo Rocha Sidney nevestesoureiro Adjunto: Adriana Costa e Forti

Rua Humaitá, 85, cj. 501

22261-000 – Rio de Janeiro, RJ

Fone/Fax: (21) 2579-0312/2266-0170

www.sbem.org.br

secretáriA executiVA: Julia Maria C. L. Gonçalves

[email protected]

departamentos científicos da SBEM – 2009/2011 Sociedade Brasileira de Endocrinologia e Metabologia

AdrEnAl E HipErtEnSãoPresidente Milena Caldato

Vice-Presidente Sonir R. Antonini

diretores Ana Claudia Latronico

Claudio Kater

Lucila L. K. Elias

Margaret de Castro

Rua dos Tamoios, 1.474, ap. 101, Batista Campos

66025-125 – Belém, PA

Fone: (91) 3223-5359/Fax: (91) 3223-8560

[email protected]

diSlipidEMiA E AtEroSclEroSE

Presidente Maria Teresa Zanella

Vice-Presidente Bruno Geloneze neto

secretário Fernando Flexa Ribeiro Filho

tesoureirA Sandra Roberta Gouvea Ferreira

diretores Fernando Giufrida

Helena Schimidt

Luciana Bahia

Marcelo Costa Batista

Gláucia Carneiro

Universidade Federal de São Paulo (Unifesp)

Rua Leandro Dupret, 365, Vila Clementino

04025-011 – São Paulo, SP

Fone: (11) 5904-0400/Fax: (11) 5904-0401

[email protected]

diABEtES MEllituS

Presidente Saulo Cavalcanti da Silva

Vice-Presidente Luiz Alberto Andreotti Turatti

secretário Antônio Carlos Pires

tesoureiro ivan Ferraz

diretores Adriana Costa e Forti

Rodrigo Lamounier

Balduino Tschiedel

suPlentes Sérgio Alala

Hermelinda Pedrosa

Rua Tomé de Souza, 830, 10o andar, cj. 1005, Savassi

30140-131 – Belo Horizonte, MG

Fone: (31) 3261-2927

www.diabetes.org.br

[email protected]

EndocrinologiA BáSicA

Presidente Vânia Maria Corrêa da Costa

Vice-Presidente Magnus R. Dias da Silva

secretário Celso Rodrigues Franci

diretores Maria Tereza nunes

Doris Rosenthal

Catarina Segreti Porto

suPlentes Ubiratan Fabres Machado

Tânia Maria ortiga Carvalho

instituto de Biofísica Carlos Chagas Filho

Universidade Federal do Rio de Janeiro

Rua Carlos Chagas Filho, 373, Cidade Universitária,

ilha do Fundão, CCS, Bloco G, sala G1060


Fone: (21) 2562-6552 / Fax: (21) 2280-8193

[email protected]

departamentos científicos da SBEM – 2009/2011

EndocrinologiA pEdiátricA

Presidente Ângela Maria Spinola e Castro

Vice-Presidente Paulo César Alves da Silva

diretores Aline Mota da Rocha

Carlos Alberto Longui

Julienne Ângela Ramires de Carvalho

Maria Alice neves Bordallo

Marília Martins Guimarães

suPlentes Claudia Braga Abadesso Cardoso

Maria Tereza Matias Baptista

Rua Pedro de Toledo, 980, cj. 52, Vila Clementino


Fone: (11) 5579-9409/8259-8277

[email protected]/[email protected]

dEpArtAMEnto dE nEuroEndocrinologiA

Presidente Mônica Roberto Gadelha

Vice-Presidente Manuel Faria

diretores Antônio Ribeiro

César L. Boguszewski

Luciana naves

Luiz Antônio de Araújo

Marcello Bronstein

suPlentes Leonardo Vieira neto

Raquel Jallad

Rua Visconde de Pirajá, 351, sala 1113, ipanema


Fone/Fax: (21) 2267-2555

[email protected]

tirEóidE

Presidente Edna T. Kimura

Vice-Presidente Laura S. Ward

secretáriA Carmen Cabanelas Pazos de Moura

diretores Ana Luiza Silva Maia

Célia Regina nogueira

Gisah Amaral de Carvalho

Mário Vaisman

suPlentes Pedro Weslley S. do Rosário

Rosa Paula Melo Biscolla

Rua Botucatu, 572, cj. 81, Vila Clementino


Fone/Fax: (11) 5575-0311

www.tireoide.org.br

[email protected]

MEtABoliSMo óSSEo E MinErAl

Presidente Victória Zeghbi Cochenski Borba

Vice-Presidente Marise Lazaretti Castro

diretores João Lindolfo C. Borges

Luiz Gregório

Cynthia Brandão

Luis Russo, Luiz Griz

Rua Cândido Xavier, 575, água Verde

80240-280 – Curitiba, PR

Fone: (41) 3024-1415 ramal 217/Fax: (41) 3342-8889

www.sobemom.org.br

[email protected]

oBESidAdE

Presidente Marcio C. Mancini

Vice-Presidente Bruno Geloneze neto

Primeiro secretário João Eduardo nunes Salles

seGundo secretário Josivan Gomes de Lima

tesoureiro Mario Kehdi Carra

rePresentAntes dA sBem Alfredo Halpern

Henrique de Lacerda Suplicy

Associação Brasileira para o Estudo da obesidade

Rua Tabapuã, 888, cj. 81/83, itaim Bibi


Fone: (11) 3079-2298/Fax: (11) 3079-1732

[email protected]

EndocrinologiA FEMininA E AndrologiA

Presidente Poli Mara Spritzer

Vice-Presidente Ruth Clapauch

diretores Alexandre Hohl

Amanda Valéria Luna de Athayde

Carmen Regina Leal de Assumpção

Dolores Perovano Pardini

Serviço de Endocrinologia, Hospital de Clínicas

de Porto Alegre, UFRGS,

Rua Ramiro Barcelos, 2350, 4o andar

90035-003 – Porto Alegre, RS

Fone: (51) 2101-8127/Fax: (51) 2101-8777

www.feminina.org.br • www.andrologia.org.br

[email protected]

coMunicAção SociAlPresidente Ruy Lyra

[email protected]

editor ABem Edna T. Kimura

memBros Ricardo M. R. Meirelles, Marisa Helena Cesar Coral, Balduino Tschiedel, Severino Farias

ÉticA E dEFESA proFiSSionAlcorreGedor Teiichi oikawa

[email protected]

Vice-correGedor ney Cavalcanti

1º VoGAl Amaro Gusmão

2º VoGAl Victor Gervásio e Silva

3º VoGAl ivana Maria netto Victória

4º VoGAl itairan de Silva Terres

5º VoGAl Maite Chimeno

SuPlentes Diana Viegas, Joaquim José de Melo, Auxiliadora Brito de Lima, Josivan Gomes da Silva, Paulo Roberto Prata Mendonça

HiStóriA dA EndocrinologiAPresidente Luiz César Povoa

[email protected]

memBros Rui M. de Barros Maciel, Thomaz Cruz

coMitê dE cAMpAnHAS EM EndocrinologiAPresidente Helena Schimid

[email protected]

memBros Luiz Antônio Araújo, Vívian Ellinger

título dE ESpEciAliStA EM EndocrinologiA E MEtABologiAPresidente Francisco Bandeira

[email protected]

Vice-Presidente osmar Monte

memBros Adelaide Rodrigues, Rui M. de Barros Maciel, Lucio Vilar, Marisa Helena Cesar Coral, Carlos Alberto Longui

suPlentes Maria Heloisa Canalli, Márcia Campos da Silva

coMitê intErnAcionAlPresidente Amélio F. Godoy Matos

[email protected]

memBros César Boguszewski, Cláudio Kater, Thomaz Cruz, Valéria Guimarães

suPlentes João Lindolfo Borges, Marcelo Bronstein

ElEitorAlPresidente Pedro Weslley S. do Rosário

[email protected]

memBros Mauro Czepielewski, Victor Gervásio e Silva, Milena F. Caldato

pAritáriA – cAAEpmemBros Ângela Maria Spínola de Castro

[email protected]

Paulo César Alves da Silva, Maria Alice neves Bordallo, Rômulo Sandrini, Luiz Eduardo Calliare, Marilza Leal nascimento

AcoMpAnHAMEnto do plAnEjAMEnto EStrAtÉgicoPresidente Ricardo M. R. Meirelles

[email protected]

memBros Ruy Lyra, Valéria Guimarães, Marisa Helena Cesar Coral, Amélio F. Godoy Matos

projEto dirEtrizEScoordenAdor Claudio Kater

[email protected]

AdrenAl e HiPertensão Milena Caldato

disliPidemiA e Aterosclerose Maria Teresa Zanella

diABetes mellitus Saulo Cavalcanti da Silva

endocrinoloGiA BásicA Vânia Maria Corrêa da Costa

endocrinoloGiA FemininA e AndroloGiA Poli Mara Spritzer

endocrinoloGiA PediátricA Ângela Maria Spinola e Castro

metABolismo Ósseo e minerAl Victória Zeghbi Cochenski Borba

neuroendocrinoloGiA Mônica Roberto Gadelha

oBesidAde Márcio C. Mancini

tireÓide Edna T. Kimura

ciEntíFicA Presidente Airton Golbert

[email protected]

memBros Presidentes Regionais, Presidentes dos Departamentos Científicos

indicAdos PelAs diretoriAs Francisco Bandeira, Adriana Costa e Forti, Laura S. Ward, Luiz Griz, Ana Claudia Latronico

VAlorizAção dE noVAS lidErAnçAS Presidente Rodrigo Moreira

[email protected]

Vice-Presidente Mônica oliveira

diretores Daniel Costa Lins, Andréa Glezer, Érica Paniago

suPlentes Daniela Rego, André Viana

rePresentAntes Carolina Garcia Soares Leães, Vânia Maria Corrêa da Costa, Erico Carvalho, Carlos Botelho, Fabíola Yukiko Miasaki

EducAção MÉdicA continuAdAPresidente Laura S. Ward

[email protected]

memBros Luiz Susin, Ruth Clapauch, João Modesto, Dalisbor Marcelo Weber Silva

EStAtutoS, rEgiMEntoS E norMASPresidente Marisa Helena Cesar Coral

[email protected]

memBros Luiz Carlos Espíndola, osmar Monte, Luiz Cesar Povoa, João Modesto

rePresentAnte dA diretoriA nAcionAl Ricardo M. R. Meirelles

comissões permanentes da SBEM – 2009/2011 Sociedade Brasileira de Endocrinologia e Metabologia

SBd – SociEdAdE BrASilEirA dE diABEtESDIRETORIa naCIOnal Da SBD (2008/2009)

Presidente Marília de Brito GomesVice-Presidentes Balduino Tschiedel Mario José Abdalla Saad nelson Rassi Reine Marie Chaves Fonseca Saulo Cavalcanti da Silvasecretário GerAl Sérgio Atala Dib2o secretário Rosane Kupfertesoureiro Antonio Carlos Lerario2o tesoureiro Domingos Augusto Malerbi

Rua Afonso Brás, 579, cj. 72/74

04511-011– São Paulo, SP

Fone/Fax: (11) 3842-4931

[email protected]

www.diabetes.org.br

secretáriA executiVA: Kariane Krinas Davison

Gerente AdministrAtiVA: Anna Maria Ferreira

ABESo – ASSociAção BrASilEirA pArA o EStudo dA oBESidAdE E SíndroME MEtABólicADIRETORIa naCIOnal Da aBESO (2008-2009)

Presidente Marcio C. ManciniVice-Presidente Bruno Geloneze neto1o secretário GerAl João Eduardo nunes Salles2o secretário GerAl Josivan Gomes de Limatesoureiro Mario Kehdi Carra

Rua Tabapuã, 888, cj. 81/83, itaim Bibi


Fone: (11) 3079-2298/Fax: (11) 3079-1732

[email protected]

www.abeso.org.br

SoBEMoM – SociEdAdE BrASilEirA dE EStudoS do MEtABoliSMo óSSEo E MinErAlDIRETORIa naCIOnal Da SOBEMOM (2009-2011)

Presidente Victória Zeghbi Cochenski BorbaVice-Presidente Dalisbor Marcelo Weber SilvasecretáriA executiVA Carolina Aguiar Moreira Kulaksecretário executiVo Adjunto Jaime Kulak Junior2o secretário executiVo Adjunto Sérgio Setsuo Maedatesoureiro GerAl Gleyne Biagginitesoureiro GerAl Adjunto Roberto Antonio Carneirodiretor cientíFico Almir Urbanetz

Rua Cândido Xavier, 575, água Verde

80240-280 – Curitiba, PR

Fone: (41) 3024-1415 ramal 217/Fax: (41) 3342-8889

www.sobemom.org.br

[email protected]

secretáriA oPerAcionAl: Dione Pires da Silva

Sociedades e Associações Brasileiras na área de Endocrinologia e Metabologia

Program & abstracts

april 30th – may 3rd, 2009Hotel serrano, gramado, brazil

O essencial é a saúde

suPPort

indexMensagem de boas vindas ............................................................. 111Bienvenidos ........................................................................................ 112Welcome message ........................................................................... 113Local organizing committee ............................................................ 114Scientific committee .......................................................................... 114LATS Executive Council ...................................................................... 116LATS Prize ............................................................................................. 120Local Organizing Committee ........................................................... 115MENSAGEM DE BOAS VINDAS ............................................................ 111Program & Abstracts .......................................................................... 107Satellite SYMPOSIA ............................................................................. 149Scientific Committee ......................................................................... 115Scientific Program .............................................................................. 129Serrano Convention Center .............................................................. 123Serrano Convention Center .............................................................. 124Sociedad Latino Americana de Tiroides ........................................ 117Speakers, Chairs & Moderators ....................................................... 150Support ................................................................................................ 108

The Latin American Thyroid Society gratefully acknowledges support for the XIII LATS Meeting from: ............................................ 116welcome MESSAGE ............................................................................ 113XIII LATIN AMERICAN THYROID CONGRESS ..................................... 129XIII Latin American Thyroid Meeting Support ............................... 116Young Investigator ........................................................................... 121

Mensagem de Boas-Vindas ....................................................... 111

Bienvenidos .................................................................................. 112

Welcome Message...................................................................... 113

Local Organizing Committee ..................................................... 115

Scientific Committee ................................................................... 115

Lats Executive Council ................................................................ 116

XIII Latin American Thyroid Meeting Support ........................... 116

Historical Outline of the Latin America Thyroid Society .......... 117

Lats Prize ........................................................................................ 120

Young Investigator ....................................................................... 121

General Information .................................................................... 122

Serrano Convention Center ........................................................ 123

Kocher Centenial Conference ................................................... 125

Scientific Program ........................................................................ 129

Satellite Symposia ........................................................................ 149

Speakers, Chairs & Moderators ................................................. 150

Abstracts – Oral Presentation .................................................... 155

Abstracts – Poster Presentation .................................................. 165

Index of Authors .......................................................................... 219

S111

mensagem de boas-Vindas

Prezados Amigos e Colegas,

Em nome da Sociedade Latino-Americana de Tireoide, é uma grande honra e prazer dar-lhes as boas-vindas ao XIII Congresso Latino-Americano de Tireoide. Estamos todos orgulhosos com a sua presença!

Primeiro, e principalmente, esse Encontro significa ciência. Nestes últimos anos, testemunhamos os notáveis avanços no manejo das doenças tireoidianas. Vários conceitos foram testados cientificamente e novas estratégias terapêuticas foram desenvolvidas. Tanto a pesquisa experimental quanto a clínica forneceram uma considerável base científica para projetar novas terapias para o câncer da tireoide. Esse evento internacional objetiva sintetizar os novos conhecimentos, bem como identificar elementos-chaves para a prática clínica e para futuras pesquisas. Além de excepcionais conferências proferidas por eminentes professores, simpósios, encontros com o especialista, apresentações orais e pôsteres, teremos um amplo espaço para discussão. Uma atmosfera informal e amigável facilitará o debate após as exposições científicas.

Eu gostaria de agradecer a todos aqueles que contribuíram de alguma forma para a realização desse evento. Uma grande parte do trabalho foi realizada pelos meus queridos amigos da Comissão Organizadora Local e pela equipe da Plenarium. É importante também enfatizar que uma ligação muito próxima e harmônica com a excelente Comissão Científica assegurou uma interação agradável e eficiente ao longo dos preparativos, o que certamente contribuiu para o sucesso na realização deste Congresso.

Finalmente, após quase dois anos de planejamento, chegou o momento de abrir as portas. Esperamos que tanto a programação científica quanto a social proporcionem a todos uma estadia muito agradável. Bem-vindos a Gramado e aproveitem o XIII Congresso Latino-Americano de Tireoide!

Ana Luiza MaiaPresidente

XIII Latin American Thyroid Congress

S112

bienVenidos

Queridos Amigos y Colegas,

En nombre de la Sociedad Latino Americana de Tiroides, es un gran privilegio y placer recibirlos en el XIII Congreso Latino Americano de Tiroides. Nosotros nos sentimos orgullosos con vuestra presencia!

Primero y principalmente este Encuentro significa Ciencia. En estos últimos años, fuimos testigos de notables avances en el tratamiento de las enfermedades tiroidianas. Concepciones previas han sido testadas científicamente y un grande número de innovaciones terapéuticas fueron efectuadas. Pesquisas experimentales y clínicas providenciaron bases científicas importantes para la realización de nuevos tratamientos para el cáncer de tiroides. Este Encuentro Internacional ha sido organizado con el objetivo de sintetizar el conocimiento. De esta forma, nuestra finalidad es identificar elementos claves de aplicación clínica y futuras pesquisas. Además, conferencias actualizadas dictadas por profesionales renombrados, simposios, encuentro con el profesor, presentaciones oral y de póster serán realizadas en un amplio espacio para discusión. Un ambiente informal y amigable facilitaran los debates después de las exposiciones científicas.

Me gustaría agradecer a todos aquellos que ayudaron de alguna forma. La mayor parte del trabajo fue realizada por mis queridos amigos de la Comisión Organizadora Local y por el equipo de la Plenarium. También, debo enfatizar que la relación directa y tranquila con la excepcional Comisión Científica aseguró una interacción placentera y eficiente durante los preparativos, que ciertamente contribuyo para la realización de este Evento.

Finalmente, después de aproximadamente dos años de planteamiento, llego el momento tan ansiado de abrir las puertas. Esperamos que tanto la programación científica como la social hagan su estadía placentera. Bienvenidos a Gramado y disfruten el XIII Congreso Latino Americano de Tiroides!

Ana Luiza MaiaPresident

XIII Latin American Thyroid Congress

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Dear Friends and Colleagues,

On behalf of the Latin American Thyroid Society, it is my great honor and pleasure to welcome you to the XIII Latin American Thyroid Congress. We are all proud to have you here!

First and foremost this Meeting means science. Over the last years we have witnessed remarkable advances in the management of thyroid diseases. Previous concepts have been tested scientifically and a large number of innovative therapeutic approaches have been developed. Experimental and clinical research has provided a considerable scientific basis for designing new therapy for thyroid cancer. This international meeting is held in an effort to synthesize this knowledge. Likewise, we aim to identify the key elements for clinical application and future research. In addition to state-of-the-art conferences delivered by distinguished professors, symposia, meet-the-expert, oral and poster presentations there will be ample room for discussion. An informal and friendly atmosphere will facilitate the debate after scientific presentations.

I would like to thank all those who have helped in many different ways. Most of the work was done by my dear friends of the Local Organizing Committee and by the Plenarium team. I must also emphasize that the close and smooth link with the outstanding Scientific Committee ensured a pleased and efficient interaction all along the preparation, which certainly contributed for the completion of this Meeting.

Finally, after almost two years of planning the time has come to open the doors. We hope that both the scientific and the social program will make your stay a pleasant one. Welcome to Gramado and enjoy the XIII Latin American Thyroid Congress!

Ana Luiza MaiaPresident

Local Organizing Committee

welcome message

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local organizing committeeAna Luiza Maia, Porto Alegre, Brazil (President)

Erika Laurini de Souza Meyer, Porto Alegre, Brazil

José Ricardo Guimarães, Porto Alegre, Brazil

Julia Pereira Lima, Porto Alegre, Brazil

Marcia K. C. Puñales, Porto Alegre, Brazil

Márcia Santos Wagner, Porto Alegre, Brazil

scientific committeeHans Graf, Curitiba, Brazil (President)

Léa Zanini Maciel, Sao Paulo, Brazil

Liliana María Bergoglio, Córdoba, Argentina

Marcos Abalovich, Buenos Aires, Argentina

Maria Tereza Nunes, Sao Paulo, Brazil

Mario Pisarev, Buenos Aires, Argentina

Nelson Wohllk, Santiago, Chile

Rosa Paula Mello Biscolla, Sao Paulo, Brazil

Tania Ortiga-Carvalho, Rio de Janeiro, Brazil

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lats executiVe councilPresident: Guilhermo Juvenal, Buenos Aires, Argentina

President Elect: Hans Graf, Curitiba, Brazil

Secretary: Ana Maria Masini-Repiso, Córdoba, Argentina

Treasurer: Eduardo K. Tomimori, Sao Paulo, Brazil

Directors:Ana Luiza Maia, Porto Alegre, Brazil

Alicia Lowenstein, Buenos Aires, Argentina

Carmen Cabezón, Buenos Aires, Argentina

Denise Carvalho, Rio de Janeiro, Brazil

Edna T. Kimura, Sao Paulo, Brazil

Fabian Pitóia, Buenos Aires, Argentina

Francisco Neves, Brasilia, Brazil

Graciela Alcaraz, Buenos Aires, Argentina

Janete Cerutti, Sao Paulo, Brazil

xiii latin american tHyroid meeting suPPort

the latin american thyroid society gratefully acknowledges support for the xiii lats meeting from:

Sanofi – Aventis Farmacêutica Ltda.

Merck Serono

Abbott Laboratórios do Brasil Ltda.

Aché Laboratórios Farmacêuticos S.A.

Genzyme do Brasil Ltda.

Johnson & Johnson do Brasil – Indústria e Comércio de Produtos para Saúde Ltda.

Tv Med – Instituto de Vídeo e Comércio Ltda.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Historical outline of tHe latin america tHyroid society

sociedad latino americana de tiroides

Geraldo Medeiros-Neto (Brazil) and Hugo Niepomniszce (Argentina)

(1). During the 13th International Congress of Endocrinology, in Rio de Janeiro, we decided to have a meeting with the purpose of providing an historical perspective of the Latin America Thyroid Association (LATS), based on our recollections of main events since its’ foundation in 1974.

(2). Foundation of LATS. In October 31st 1974, in the Sheraton Hotel, in Buenos Aires, Argentina, during the Panamerican Congress of Endocrinology, organized by Roberto Soto, Geraldo Medeiros-Neto (Brazil) transmitted to a group of thyroidologists, presents at the Meeting that in a personal conversation with David Solomon (from California, USA), at that time from the Board of Directors of the American Thyroid Association, that it would be nice and useful that the Latin-American Endocrinologists interested in Thyroid Disease should consider to charter an Organization, under the name of Latin America Thyroid Society. Therefore an official meeting took place with the presence of the following thyroidologists:

1. Noe Altschuler (Argentina)2. Walter Bloise (Brazil)3. Osvaldo J. Degrossi (Argentina)4. Pablo Fletcher (Panama)5. Eduardo Gaitan (Colombia)6. Jorge Maisterrana (Mexico)7. Geraldo Medeiros-Neto (Brazil)8. Willian Nicolau (Brazil)9. Hugo Niepomniszce (Argentina)10. Gustavo Pineda (Chile)11. Mario Pisarev (Argentina)12. Eduardo Pretell (Peru)13. José Varea Teran (Ecuador)14. Manfredo Weinstein (Argentina)

During this meeting Medeiros-Neto mentioned the suggestion of David Salomon and made a motion that the new “Sociedad Latino Americana de Tiroides” should be founded. The motion was seconded and approved by all the thyroidologists present at the meeting. Also it was decided to indicate a provisional Executive Committee to take the first steps to consolidate the new scientific Society. Walter Bloise motioned that Geraldo Medeiros-Neto could be elected as the first President of LATS, with Hugo Niepomniszce as General Secretary, and Eduardo Pretell as

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vice-president. Also the other thyroidologists present at the Meeting should be designated as delegates of their respective countries. Gustavo Pineda (Chile), Eduardo Gaitan (Colombia), Pablo Fletcher (Panama), Jorge Maisterrena (Mexico) e J. Varea-Teran (Ecuador). Later on, this first Board of Officers constituted the official directors of the LATS, with four years of mandate (1974-1978).

(3). Members that were considered as founders: at the meeting in 1974 it was decided that all presents should be considered as co-founders of the new organization. All new members that would join LATS until December 1975 should also be considered as co-founders. In 1975 Niepomniszce prepared the provisional By-laws that were approved by LATS members. Later on the By-laws were adapted to the Brazilian Civil Code and registered in the notarial office in Sao Paulo (Brazil) in 1976. An year later it was formally chartered and registered at the Ministry of Justice in Brazil with all the proper rights to start its activities as a Scientific Society.

(4). The first years of LATS during the few years of existence of LATS (1974-1978) Medeiros-Neto, as President decided to organize on a yearly basis scientific meetings in Sao Paulo, Brazil, during the official Course on Thyroid Diseases, at the Hospital das Clinicas, University of Sao Paulo Medical School. With the support of the Pharmaceutical Industry, several members of the LATS were invited to come to Sao Paulo to participate in these meetings as speakers. Moreover an official meeting of LATS members was simultaneously arranged and new ideas and suggestion were made.

(5). International recognition of LATS: in the International Thyroid Congress in Boston, USA, in 1975, LATS was officially recognized and accepted as the new “sister” of the already chartered Thyroid Societies, as the American Thyroid Association and the European Thyroid Association. Later on the Asia and Oceania Thyroid Association joined this group.

(6). International Thyroid Congress: in Sidney, Australia, in 1980, during the 8th Intl. Thyroid Congress, LATS proposed that this international meeting could take place in South America. Indeed, the proposal was to have the 1985 Intl. Thyroid Congress in Sao Paulo (Brazil) and in 2005 in Buenos Aires (Argentina), based on a system that would give to each “sister” Society the right to have the ITC every 20 years. This rule was approved by the International Committee of the Thyroid Societies representatives in Sydney, Australia.

(7). First meetings of LATS: the first official meeting of LATS was organized in 1981 by Hugo Niepomniszce in Mar del Plata, Argentina, and attended by a great number of endocrinologists of South America. This first event helped to consolidate the new Society. In 1983 Eduardo Pretell was the organizer of the second meeting of LATS in Lima, Peru. In 1985 Sao Paulo (Brazil) was selected as the site for the 9th International Thyroid Congress, with Geraldo Medeiros-Neto as President. This meeting gathered more than 1,100 delegates from several countries and was considered as an important Scientific and Social success.

In 1986 the Fourth LATS Congress was organized by Maria Cristina Blanco in Caracas, Venezuela. In 1989, Fierro-Benites from Ecuador, could not find support for the LATS meeting in Quito, Ecuador, and therefore, Joao H. Romaldini and

Historical outline of the Latin America Thyroid Society

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Rui Maciel were able to have the 5th LATS meeting in Sao Paulo, Brazil in 1991. Two years later, in 1993, Mario Pisarev organized the 6th LATS meeting in Buenos Aires, Argentina. In 1995, Toronto (Canada) was selected as the site to host the 11th Intl. Thyroid Congress and several LATS members were present at this meeting both as speakers or presenting scientific papers.

(8). Board of Directors of LATS after the first Board of Directors (1974-1978), the following members of LATS were elected as Presidents with a mandate of four years:

Eduardo Pretell 1978-1982Eduardo Gaitan 1982-1986Jorge Maisterrena 1986-1990

In 1990 it was motioned and approved that the Board of Directors would have a mandate of two years and the following Presidents were:

Mario Psarev 1991-1993João H. Romaldini 1993-1995Gustavo Pineda 1995-1997Hugo Niepomniszce 1997-1999Rui Maciel 1999-2001Aldo Coleoni 2001-2003Doris Rosenthal 2003-2005Nelson Wolhk 2005-2007Guillermo Juvenal 2007-2009

(9). Meetings of LATS and respective organizers

1997 Viña de Mar, Chile (Gustavo Pineda)1999 Foz do Iguacu, Brazil (Hans Graf)2001 Rio de Janeiro, Brazil (Carmen Cabanelas Pazos-Moura)2003 Cordoba, Argentina (Aldo Coleoni)2005 Buenos Aires, Argentina (International Thyroid Congress)2007 Santiago de Chile (Nelson Wolhk)2009 Gramado, Brazil (Ana Luiza Maia)

(10). This Historical “resume” of LATS shows very nicely that LATS has emerged from a small group of scientists interested in Thyroid Diseases to a strong Association that equals the other Thyroid Societies (ATA, ETA and AOTA) and contributes to expand the knowledge of Thyroid Diseases in Latin America. More specifically it has been quite active, under the leadership of Eduardo Pretell (from ICCIDD) to improve Iodine Nutrition in Latin America. Contributions of our members to many aspects of thyroid disease (Thyroid cancer, dyshormono-genesis, thyroid nodular disease, Graves’ disease and autoimmunity, among others) have been recognized in the medical literature. Moreover members of LATS have been actively participants in many of the Thyroid meeting around the world and certainly they integrate the thyroid scientific community.

Historical outline of the Latin America Thyroid Society

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lats PrizeThe LATS Prize is awarded at each LATS Congress to an Active member of the Society who has made outstanding contributions to thyroid research over a considerable period of time. The Executive Committee will make the award. The Executive Committee can indicate a special board of experts, not necessarily members of LATS, to work as referees. The final decision will be made by the Executive Committee. Candidates for the Prize may be proposed and seconded by any two Active members of SLAT. The proposal should include the candidate’s curriculum vitae (of no more than 10 pages) and a short citation (of no more than 2 pages) indicating the nature of candidate’s personal contribution to thyroid research to the Secretary. The recipient is asked to deliver a lecture at the LATS Congress.

Past Winners

2007 Mário Vaisman

2005 Héctor Rubén Harach

2003 João H. Romaldini

2001 Gregorio Chazenbalk

2000 Antonio C. Bianco

1999 Eduardo A. Pretell

1997 Doris Rosenthal

1995 J. Enrique Silva

1993 Hugo Niepomniszcze

1991 Rui M. B. Maciel

1990 Mario Pisarev

1985 Eduardo A. Gaitan

1983 Aldo Coleoni

1980 Geraldo A. Medeiros-Neto

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young inVestigatorThe LATS Prize – young investigator – is awarded at each LATS Congress to 2 young members of the Society (less than 40 years of age) presenting an accepted paper at the Congress. The categories under which the prize will be given are: (1) clinical and (2) basic research. The young investigators must be the first author and must be present at the Congress and the work presented must have been made in full in a country of Latin America.

Past Winners

2007 Flavia Roche Moreira Latini – basic Helton Estrela Ramos – clinical

2005 Maria Izabel Chiamolera – basic Cleber P. Camacho – clinical

2003 Marcia Khaled Puñales – clinical Alejandra Dagrosa – basic

2001 Gisele Giannocco – basic Janete Maria Cerutti – clinical

Leonardo Gabriel Bazzara – basic Maria Carolina P. do Nascimento – clinical

1999 Magnus R. Dias da Silva – clinical Tania M. Ortiga Carvalho – basic

1998 Claudia G. Pellizas – basic Marcelo Branco – basic

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general information

Venue

Centro de Convenções SerranoAvenida das Hortênsias, 1.480Gramado – RS – Brasil95670-000Tels.: 55-51-3012.7240/3022.7200

RegistRation Desk

The registration and Service desk is set up at the conference venue hotel, ground floor on the following Schedule: April 30th to May 2nd, 2009, from 08h00 to 18h00; May 3rd, 2009, 08h00 to 17:00.

PResentations

The slide desk will be open from 8h00 to 18h00, ground floor. PowerPoint is the preferred format for presentation. Presenters must check in their presentation at least 2 hours before their session begins. All conference rooms are fully equipped with a PC for presentation. It will not be possible to use slides or overhead projection.

PosteR DisPlay

Posters will be displayed at the designated area located in the ground floor. Poster presenters are personally responsible for affixing and removal of their posters. Assistance and material for mounting the poster will be provided by the congress’ secretariat. Poster size should not exceed 0.90m in width and 1.00m in height. Presenters should put up their posters at the number assigned to their abstracts by 10h00 – Friday, May 1st. The posters will be displayed during all the time of the meeting. The presenter must be present during the time dedicated for Poster Discussion (May 3rd, 17h00). All posters should be removed at the end of the congress.

BaDges

Badges must be worn at all times and to all events during the meeting.

language anD tRanslation seRVice

The official language of the meeting is English. However Presenters may also give their talk in Portuguese or Spanish. There will be English-to-Portuguese translation service on-site for the conferences and symposia with International Speakers.

Mail anD Messages

Computer facilities will be provided to all participants for internet access to email. The se facilities will be located at the ground floor, near to the Registration Desk. Additionally, free Wi-Fi wireless internet access is available in the entire Convention Center.

tickets anD tRansfeRs

The Official Agencia (Poster area, ground floor) will be available for informations from 9h00 to 17h00.

social eVents

Opening Ceremony – Welcome Coquetel (Room Erico Verissimo)19h30, Thursday, April 30th, 2009All participants are invited. Please wear your name badge.

Gala Dinner (Room Erico Verissimo)21h00, Saturday, May 2nd, 2009 Invitation required for admittance.

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serrano conVention centerground floor

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serrano conVention centerfirst floor

KocHer centenial conference

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Thursday, April 30th, 2009

Nilton Herter, Porto Alegre, Brazil (Chairman)

scientific committeeCelso U. M. Friguglietti, Sao Paulo Erivelto Volpi, Santo André Jose Higino Steck Fo, Campinas Marco Aurélio V. Kulcsar, Sao Paulo

8h30 confeRence 1

kocher and the thyroid surgery history Claudio R. Cernea, Sao Paulo

Chair: Daniel Sperb, Porto Alegre Debator: Cláudio Rogério Alves de Lima, Salvador

9h15 syMPosiuM 1

thyroidectomy: “state of the art” Chair: Alberto Ferraz, Sao Paulo Debators: Onivaldo Cervantes, Sao Paulo Rogério Dedivitis, Santos

1. Forming new specialists – teaching thyroid surgery Lenine Garcia Brandão, Sao Paulo 2. Minimally invasive thyroidectomy – indications and results Erivelto Volpi, Santo André 3. Intraoperative laringeal nerve monitorization (ILNM), when, how and why? Gregory Randolph, Boston (USA)4. ILNM – experience and results Henning Dralle, Halle (Germany)5. Post-surgical hypoparathyroidism, how to prevent and treat? Fernando Luiz Dias, Rio de Janeiro 6. Post-surgical hematomas Antonio José Gonçalves, Sao Paulo

Discussion

theater lupicinio Rodrigues


Kocher Centenial Conference

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11h00 coffee BReak

11h15 confeRence 2

actual treatment of medullary thyroid cancer Henning Dralle, Halle (Germany)

Chair: Ana Luiza Maia, Porto Alegre Debators: José Francisco de Gois Filho, Sao Paulo Nelson Wohllk, Santiago de Chile

12h00 lunch

13h00 syMPosiuM 2

hyperthyroidism Chair: Vergilius José Furtado de Araújo Filho, Sao Paulo Debators: Evandro Vasconcelos, Curitiba Lea Maria Zanini Maciel, Ribeirão Preto

1. Antithyroid drugs treatment, indications and limitations Ana Beatriz Pinotti Miklos, Sao Paulo 2. Why indicate surgery? José Higino Steck, Campinas 3. 131I therapy for all patients? Flávio Zelmanovitz, Porto Alegre 4. Recidive treatment José Luiz Novelli, Rosario

Discussion

14h15 confeRence 3

thyroid reoperations: “pearls and pitfalls” Gregory Randolph, Boston (USA)

Chair: Jorge Pinho, Recife Debators: Flávio Carneiro Hojaij, Sao Paulo Roberto de Araújo Lima, Rio de Janeiro





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15h00 coffee BReak

15h15 syMPosiuM 3

Multinodular goiter – how i treat Chair: Luis Soto-Diaz, Santiago, Chile Debators: Rui M. B. Maciel, Sao Paulo Marcio Abrahão, Sao Paulo

1. Clinical Follow-up, observe or intervene João Hamilton Romaldini, Sao Paulo2. Indications of 131I therapy Cláudio Albino, Maringá3. Suppressive therapy Eduardo Tomimori, Sao Paulo 4. Thyroidectomy, indications and extension Marco Aurélio V. Kulcsar, Sao Paulo 5. Intrathoracic goiter, clinical treatment Hans Graf, Curitiba 6. Intrathoracic goiter, surgical treatment Marcos Brasilino de Carvalho, Sao Paulo

Discussion

17h00 syMPosiuM 4

Differentiated thyroid carcinoma – new approaches Chair: Gilberto Vaz Teixeira, Florianópolis Debators: Alfio Tincani, Campinas Mario Vaisman, Rio de Janeiro

1. Micropapillary carcinoma – What is the best surgery? Celso Ubirajara M. Friguglietti, Sao Paulo 2. Post-surgical approach to the papillary carcinoma Fabian Pitóia, Buenos Aires 3. Actual indications of cervical lymph node surgery Carlos Neutzling Lehn, Sao Paulo 4. Locally invasive thyroid cancer Luiz Paulo Kowalski, Sao Paulo 5. Tireoglossal duct cancer Nilton Herter, Porto Alegre

Discussion

19h30Xiii latin aMeRican thyRoiD congRess oPening ceReMony

RooM eRico VeRíssiMo




scientific Program

xiii latin american tHyroid congress

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Friday, May 1st, 2009

8h00 confeRence 1

approach to differentiated thyroid cancer Richard Kloos, Ohio (USA)

Chairs: Guillermo Juvenal, Buenos Aires Hans Graf, Curitiba

9h00 oRal session 1

Basic Chairs: Maria Tereza Nunes, Sao Paulo Mario Pisarev, Buenos Aires

oR. 01. Smurfs, TGFβ Pathway regulation ubiquitin ligases, are highly expressed in papillary thyroid carcinoma. Fiore APZP, Raimundo SG, Ricarte-Filho JCM, Kimura ETCell & Developmental Biology Department, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

oR. 02. Efeito do tratamento agudo com iodeto e perclorato na expressão, comprimento da cauda poli-A e tradução do mRNA do cotransportador de sódio-iodeto (NIS) em ratos e células pccl3.Serrano-Nascimento C, Goulart-Silva F, Nunes MTDepartment of Physiology and Biophysics, University of Sao Paulo, Sao Paulo, Brazil

oR. 03. The oncogene BRAFt1799a increased notch 1 expression in thyroid cell line and in transgenic mice. Yamashita AS, Rezende E, Fuziwara C, Gonçalves SR, Kimura ETDepartment of Cell Biology and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

oR. 04. Intestinal Na + /I- symporter (NIS) expression is regulated at post-transcriptional level by high concentrations of iodide. Nicola JP1, Susperreguy S1, Carrasco N2, Masini-Repiso AM1

1Centro de Investigaciones en Bioquímica Clínica e Inmunologia. CIBICI-CONICET. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba, Córdoba, Argentina; 2Department of Molecular Pharmacology. Albert Einstein College of Medicine, New York, USA

Room erico Veríssimo


Scientific Program – Friday, May 1st, 2009

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9h00 oRal session 2

clinical Chairs: Nelson Wohllk, Santiago de Chile Rosa Paula Biscolla, Sao Paulo

oR. 05. The role of RET genetic variants in hereditary medullary thyroid carcinoma. Siqueira DR, Rocha AP, Meotti C, Estivalet A, Puñales MK, Maia ALThyroid Section, Endocrine Divison, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

oR. 06. NIS mRNA levels are lower in papillary thyroid carcinomas but do not correlate with NIS protein localization in the neoplastic follicular cells. Morari EC1, Marcello MA1, Cunha LL1, Guilhen ACT1, Vassallo J2, Soares FA3, Ward LS1

1Molecular Genetics of Cancer Laboratory, Faculty of Medical Sciences (FCM), State University of Campinas (Unicamp); 2Laboratory Investigative and Molecular Pathology, CIPED, Faculty of Medical Sciences (FCM), State University of Campinas (Unicamp), Campinas, Brazil; 3Department of Pathology, Hospital AC Camargo – Antonio Prudente Foundation, Sao Paulo, Brazil

oR. 07. Percutaneous ethanol injection treatment of cervical lymph node metastases of papillary thyroid cancer. Perez CLS1, Mesa Jr C1,Trippia M2, Carvalho GA1, Graf H1

1Endocrinology Unit (SEMPR), Hospital de Clínicas da Universidade Federal do Paraná; 2Radiology Unit, Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil.

oR. 08. Nuclear chromatin texture transformation may be related to the expression of genes involved in tumor progression and help identify papillary thyroid carcinomas with aggressive behavior.Ferreira RC, Morari EC, Silva JR, Guilhen ACT, Adam RL, Leite NJ, Matos PS, Assumpção LM, Vassalo J, Soares F, Metze K, Ward LSFaculty of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil

10h00 eXhiBitions/coffee BReak/PosteR DisPlay

10h15 syMPosiuM 1

thyroid cancer Chairs: Mario Vaisman, Rio de Janeiro José Luis Novelli, Rosário

1. LATS consensus on differentiated thyroid cancer management Fabian Pitóia, Buenos Aires2. TRH stimulation on TSH: an alternative for rhTSH? Jorge Jara Yorg, Assuncion 3. High risk thyroid cancer: an update on new approaches Ana Hoff, Sao Paulo 4. FDG PET in thyroid cancer Richard Kloos, Ohio (USA)

Discussion



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10h15 syMPosiuM 2

Molecular and diagnostic aspects on thyroid cancer Chairs: Lea M. Z. Maciel, Ribeirão Preto Luis Soto-Díaz, Santiago de Chile

1. MEN 2 and the RET protooncogene: from bedside to bench to bedside. Henning Dralle, Halle (Germany)2. Antiproliferative signaling in thyroid cancer Edna Kimura, Sao Paulo 3. Molecular markers and thyroid cancer Janete Cerutti, Sao Paulo 4. Perspectives for an improved classification of thyroid tumors Ralf Paschke, Leipzig (Germany)

Discussion

Meet-the-eXPeRt 1

Preoperative assessment of differentiated thyroid carcinoma Gregory Randolph, Boston (USA)

Chairs: Claudio R. Cernea, Sao Paulo Erivelto Volpi, Sao Paulo


satellite syMPosiuM 1 – MeRck-seRono

13h00 confeRence 2

Diagnostic and therapeutic perspectives for thyroid autonomy Ralf Paschke, Leipzig (Germany)

Chair: Ana Luiza Maia, Porto Alegre



Room antônio casaccia



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14h00 syMPosiuM 3

thyroid nodules Chair: Ana Orlandi, Buenos Aires

1. Which nodules should undergo FNAB? Rosalinda Camargo, Sao Paulo 2. Nodular goiter in elderly patients Marta Schnitman, Buenos Aires 3. The thyroid as a victim of the insulin resistance syndrome Hugo Niepomniszcze, Buenos Aires 4. Is the management of thyroid nodules and in accordance with recent

consensus guidelines? Gisah Amaral de Carvalho, Curitiba

Discussion

syMPosiuM 4

thyroid function regulation

Chairs: Doris Rosenthal, Rio de Janeiro Claudia Pellizas, Córdoba

1. Regulation of NIS expression Maria Tereza Nunes, Sao Paulo 2. Regulation of thyronine deiodinase activity in the thyroid gland Carmen Cabanelas Pazos-Moura, Rio de Janeiro 3. Insights on TLR-4 pathway interaction with thyroid cell Ana María Masini-Repiso, Córdoba 4. New Concepts in the regulation thyroid function Guillermo Juvenal, Buenos Aires

Discussion

thyroid Debate 1

Moderator: Laura Ward, Campinas

Second generation thyroglobulin assays methods in the differentiated thyroid cancer follow-upRui M. B. Maciel, Sao Paulo Stimulated thyroglobulin in the differentiated thyroid cancer follow-upRichard Kloos, Ohio






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15h45 PosteR DeBate 1

thyroid cancer Chairs: Rui M. B. Maciel, Sao Paulo Valéria Guimarães, Brasília

Po. 065. Patients with familial papillary thyroid cancer have a similar outcome than those with sporadic tumors. Pitoia F, Cross G, Salvai ME, Nuñez S, Haseitel M, Abelleira E, Niepomniszcze HDivision of Endocrinology - Hospital de Clínicas - University of Buenos Aires

Po. 066. Patients with insulin resistance have less aggressive papillary thyroid cancers. Rezzónico JN1, Rezzónico M1, Pusiol E1, Pitoia F2, Niepomniszcze H2

¹Centro Privado de Endocrinología, Mendoza and ²Division of Endocrinology. Hospital de Clínicas - UBA; Buenos Aires, Argentina

Po. 070. Expression of vascular endothelial growth factor-A (VEGF-A) and its receptor (VEGFR-2) in medullary thyroid carcinoma.Capp C, Siqueira D, Wajner SM, Meurer L, Assis Brasil B, Maia ALThyroid Section, Endocrine Division and Pathology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.

Po. 074. A obesidade dobra o risco de desenvolvimento de câncer diferenciado da tiroide. Castaldi SA1, Marcello MA1, Cunha LL1, Assumpção LVM2, Ward LS1

1Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas da Unicamp; 2Ambulatório de Câncer da Tiroide, Disciplina de Endocrinologia, Faculdade de Ciências Médicas da Unicamp; Campinas, Brasil

Po. 075. A presença de linfócitos infiltrantes está associada com características de agressividade tumoral, com o prognóstico e com a expressão de genes supressores tumorais nos carcinomas papilíferos da tiroide.Cunha LL1, Morari EC1, Guilhen ACT1, Bufalo NE1, Vassallo J2, Soares FA1, Ward LS1

1Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas da Unicamp; 2Departamento de Anatomia Patológica, Faculdade de Ciências Médicas da Unicamp; Campinas, Brasil

Po. 093. Marcación prequirúrgica con arpón metálico en metástasis cervicales de carcinoma papilar tiroideo. Faure E1, Lambertini R3, Farías P3, Figari M4, Villar A2, Simkin D1Servicio de Endocrinología; 2Servicio de Cirugía, Complejo Médico PFA Churruca-Visca; 3Servicio de Diagnóstico por Imágenes; 4Servicio de Cirugía, Hospital Italiano de Buenos Aires; Buenos Aires, Argentina

Po. 114. Microcarcinoma papilar de tiroides ¿se puede diferenciar el comportamiento agresivo inicial? Munizaga F1-2, Lioi X1-2, Hidalgo S1, Munizaga C3

1Hospital San Borja-Arriarán, Unidad de Endocrinología; 2Universidad de Chile, Campus Centro; 3Universidad Católica del Norte; Santiago, Chile

Po. 128. Proliferacion epitelial: identificacion de factores que aumentan el riesgo de malignidad. Corino M, Migliano M, Morelli S, Bacchini V, Moreno A, Padin RHospital Nacional Prof. Alejandro Posadas; Buenos Aires, Argentina

Po. 078. Impact of retinoic acid on advanced thyroid carcinoma – 4 years of follow-up. Coelho SM1, Vaisman F1, Buescu A1, Corbo R2, Carvalho DP3, Vaisman M1

1Serviços de Endocrinologia; 2Medicina Nuclear; HUCFF; 3Laboratório de Fisiologia Endócrina, IBCCF; Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Po. 127. High prevalence of suspicious fine-needle aspiration cytology in thyroid nodules associated with positive thyroglobulin antibodies but not with thyroid peroxidase antibodies. Sá MBR1, Villagelin D1-2, Santos RB1, Cunha M1, Romaldini JH1-2

1Departament of Endocrinology, Pontifícia Universidade Católica de Campinas, Campinas, Brazil; 2Hospital Servidor Publico Estadual; Sao Paulo, Brazil



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clinical thyroidology Chairs: Mario Pisarev, Buenos Aires Gisah Amaral de Carvalho, Curitiba

Po. 002. Absence of PAX-8 and TSH receptor genes mutations in patients with thyroid dysgenesis. Brust ES1, Beltrao CB1, Chammas MC2, Juliano AG2, Watanabe T2, Sapienza MT2, Marui S1

1Laboratório de Endocrinologia Celular e Molecular, Unidade de Tireoide, LIM 25; 2Departamento de Radiologia, Inrad, Hospital das Clínicas, Faculdade de Medicina da Universidade de Sao Paulo; Sao Paulo, Brazil

Po. 007. Avaliação ultrassonográfica da tireoide, determinação da iodúria e concentração de iodo em sal de cozinha utilizado por escolares de Ribeirão Preto, Sao Paulo, Brasil. Alves MLD1, Duarte GC2, Navarro AM1, Tomimori EK2

1Curso de Medicina da Universidade de Ribeirão Preto, Brasil; 2Disciplina de Tiroide – Hospital das Clínicas da Faculdade de Medicina de Sao Paulo, Brasil

Po. 009. Treatment of Graves’ ophthalmopathy with an antagonist of PPAR-gamma: preliminary results. Bloise W, Mimura LY, Moura J, Nicolau WGraves’ Ophthalmopathy Section-Thyroid Unit – Hospital das Clínicas – School Medicine of Sao Paulo; Sao Paulo, Brazil

Po. 035. Evaluation of thyroid patients infected by hepatitis C virus: correlation with polymorphisms of CTLA-4 gene. Lima EU1, Barros RK3, Knobel M2, Mendes-Correa MC3, Zambrini H3, Marui S1

1Laboratory of Cellular and Molecular Endocrinology Unit of Thyroid-LIM-25; 2Endocrine Division; 3Division of Infectious Diseases, Hospital das Clinicas, Faculty of Medicine of the University of Sao Paulo; Sao Paulo, Brazil

Po. 015. Comparison of different doses of radioiodine in severe Graves hyperthyroidism: a clinical trial with historical control. Dora JM, Machado WE, Andrade VA, Maia ALThyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre; Porto Alegre, Brazil

Po. 024. Hypothyroidism causes width’s reduction in testicular germinative epithelium. Romano RM, Salgado RM, Nunes MTDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo; Sao Paulo, Brazil

Po. 042. Detecção da resistência ao hormônio tireoidiano pela triagem neonatal. Magalhães PKR, Maciel LMZDivisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto; Ribeirão Preto, Brasil

Po. 046. Bone and mineral metabolism in resistance to thyroid hormone. Dare GLR, Magalhães PKR, de Castro M, Maciel LMZDivision of Endocrinology, Department of Internal Medicine, School of Medicine of Ribeirão Preto; Ribeirão Preto, Brazil

Po. 054. Low triiodothyronine (T3) plasma levels in congestive heart failure (CHF) are associated with other neurohormonal and inflammatory prognostic markers of the disease. Brenta G, Thierer J, Vainstein N, Acosta A, Boero L, Sutton M, Brites FCardiovascular Institute of Buenos Aires (ICBA) School of Pharmacy and Biochemistry, University of Buenos Aires Dr. Cesar Milstein Hospital; Buenos Aires, Argentina

Po. 064. Eliminacion de la deficiencia de yodo en Paraguay y riesgo de exceso de yodo. Ovelar EC, Redondo J, Zarza Z, González N, Jara J, Pretell EAInstituto Nacional de Alimentación y Nutrición, Ministerio de Salud Pública y Bienestar Social; Asunción, Paraguay



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Molecular and cellular biology Chairs: Vania Costa, Rio de Janeiro Claudia Pellizas, Córdoba

Po. 020. Human DuOx 2 promoter activity regulation by hormones and transcripition factors. Cardoso LC1, Querino AL1, Costa MEWF2, Carvalho DP1, Santisteban P3

1Laboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; 2Laboratório de Biologia Molecular e Bioquímica de Proteínas, IBCCF, UFRJ; Rio de Janeiro, Brazil; 3Instituto de Investigación Alberto Sols, Universidad Autónoma de Madrid, Madrid, Spain

Po. 039. A novel mutation in selenocystein binding protein type 2 gene is associated with abnormal thyroid hormone metabolism: case report.Leiria LB, Meyer ELS, Dora JM, Maia ALThyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Po. 048. Genomic and non-genomic intracellular pathways involved in thyroid hormona mediated T lymphoma cell proliferation. Barreiro Arcos ML1, Farías RN2, Klecha AJ1-3, Sterle HA1, Genaro AM11-3, Cremaschi GA1-3

1Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA); 2Instituto Superior de Investigaciones Biologicas (INSIBIO), CONICET, Universidad de Buenos Aires; Buenos Aires, Argentina

Po. 124. Arginase II and nitric oxide sintase (NOS): pathogenesis pathways of thyroid tumors. Sousa MSA, Latini FRM, Cerutti JMGenetic Basis of Thyroid Tumors Laboratory, Division of Genetics and Division of Endocrinology, Federal University of Sao Paulo; Sao Paulo, Brazil

Po. 051. Glucocorticoids prevent thyroid hormone action at the level of the initiation of the immune response. Role of dexamethasone on triiodothyronine (T3) effects on mice dendritic cell characteristics. Montesinos MM1, Mascanfroni ID1, Alamino VA1, Susperreguy S1, Masini-Repiso AM1, Rabinovich GA2, Pellizas CG1

1CIBICI-CONICET. Dpto. de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina; 2Laboratorio de Inmunopatología. IBYME-CONICET; Buenos Aires; Argentina

Po. 055. TSH increases nitric oxide synthase III expression through a PKA-dependent AKT activation. Fozzatti L, Nicola JP, Nazar M, Velez ML, Lucero AM, Pellizas CG, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunologia, CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

Po. 057. Iodine excess increases seleproteins expression in rat thyroid. Fuziwara CS, Raimundo SG, Leoni SG, da Silva MJ, Ricarte-Filho JC, Kimura ETDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo; Sao Paulo, Brazil



S137

Po. 058. Detecção de fitoquímicos capazes de promover o aumento da captação tireoidea de iodeto in vitro e in vivo. Santos MCS, Gonçalves CFL, Souza ECL, Braga WMO, Ginabreda MGP, Ferreira ACF, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brasil

Po. 122. Lipopolysaccharide stimulates cell proliferation and modifies cell cycle-related proteins in the FRTL-5 thyroid cell line. Nazar M, Nicola JP, Vélez ML, Pellizas CG, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

Po. 061. A novel role of the NFKb transcription factor in the TSH-regulated thyroid gene expression. Nicola JP, Nazar M, Mascanfroni ID, Pellizas CG, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

16h45 confeRence 3

thyronamines Thomas S. Scanlan, Oregon (USA)

Chairs: Francisco Neves, Brasília Gisah Amaral de Carvalho, Curitiba

18h00 satellite syMPosiuM 2 – genzyMetheater lupicinio Rodrigues



S138

Saturday, May 2nd, 2009

8h00 confeRence 4

lats Prize Chairs: Guillermo Juvenal, Buenos Aires Hans Graf, Curitiba

9h00 oRal session 3

Basic Chairs: Tania M. Ortiga-Carvalho, Rio de Janeiro Carmen Cabezón, Buenos Aires

oR. 09. Novel involvement of NFkB subunit P65 in the lipopolysaccharide-induced NA+/I- symporter gene expression. Nicola JP, Nazar M, Mascanfroni I, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología. CIBICI-CONICET. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba; Córdoba, Argentina

oR. 10. Evidência de ação não genômica do hormônio tireoidiano (HT) no controle da expressão gênica e proteica do transportador de glicose Glut4 em células 3T3-L1 (adipócitos). Teixeira SS, Serrano-Nascimento C, Poyares LL, Machado UF, Nunes MTDepartamento de Fisiologia e Biofísica, ICB, USP; Sao Paulo, Brazil

oR. 11. Diferenças tecido-específicas na regulação da expressão da glutationa s-transferase por hormônios tireoideanos. Faustino LC, Pires RM, Lima AC, Carvalho TMOLaboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ); Rio de Janeiro, Brasil

oR. 12. Estrogen increases thyroid hydrogen peroxide generation by dual oxidase in female rats. Ferreira ACF, Pantaleão TU, Freitas ML, Ginabreda MGP, Cardoso LC, Costa VMC, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brasil

oRal session 4

clinical Chairs: Gustavo Caldas, Recife Léa M. Z. Maciel, Ribeirão Preto

oR. 13. A novel syndrome related to selenoproteins deficiency. Azevedo MF1-3, Barra GB2, Castro LC1, Amato AA1-3, Velasco LFR2, Godoy P2, Naves LA3, Neves FAR1

1Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasília (UnB); 2Sabin Institute and Laboratory of Clinical Analysis; 3Department of Endocrinology, University of Brasília (UnB); Brasília, DF, Brazil

oR. 14. Effects of pentoxifylline, nicotinamide/allopurinol and methylprednisolone in the proptosis and inflammatory markers in patients with Graves’ ophthalmopathy (GO). Fernandes LPS1, Cruz JB1, Pivotto DR1, Jorge EN2, Padovani CR3, Nogueira CR1, Mazeto GMFS1

1Endocrinology Division Internal Medicine Departament; 2Ophthalmology Departament; 3Biostatistics Departament, Faculdade de Medicina de Botucatu (Unesp)




Scientific Program – Saturday, May 2nd, 2009

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oR. 15. CTLA-4 318 polimorphisms are a factor of risk for Graves’ ophthalmopathy in Brazilian patients. Bufalo NE1, Santos RB2, Leite JL1, Guilhem MS1, Silva ACN1, Romaldini JH2, Ward LS1

1Medical Clinical, Lab. Gemoca, Unicamp; 2Division of Endocrinology, PUC-Campinas; Campinas, Brazil

oR. 16. Herpesvirus type 7 infection is a factor of risk for Graves’ disease in Brazilian but not in dutch patients. Leite JL1, Bufalo NE1, Santos RB2, Vos XG3, Romaldini JH2, Wiersinga WM3, Ward LS1

1Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences School, State University of Campinas (Unicamp); 2Division of Endocrinology, Department of Medicine, Catholic University of Campinas; Campinas, Brazil; 3Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands


10h15 syMPosiuM 5

hyperthyroidism Chairs: Alicia Gauna, Buenos Aires Alexandre Buescu, Rio de Janeiro

1. Sources of peripheral T3 in humans: implications for therapy P. Reed Larsen, Boston (USA)2. Cardiometabolic effects of subclinical hyperthyroidism José Agusto Sgarbi, Marília 3. New approaches in the toxic MNG treatment Claudio Albino, Maringá 4. Thyrotoxicosis and bones: is there a risk for osteoporosis? Ulla Feldt-Rasmussen, Kopenhagen

Discussion

syMPosiuM 6

thyroid hormone action Chairs: Tania M. Ortiga-Carvalho, Rio de Janeiro Graciela Jahn, Mendoza

1. Thyroid hormone analogs: useful biological probes and potential therapeutic agents

Thomas S. Scanlan, Oregon (USA)2. Chemistry, biology, and medicine of new thyroid hormone analogs Igor Polikarpov, São Carlos 3. Thyroid hormone resistance with and without TR-beta mutations Francisco Neves, Brasília

Discussion




S140

10h15 Meet-the-eXPeRt 2

overview of the iodine status in latinameric Eduardo Pretell, Peru

Chair: Geraldo Medeiros-Neto, Sao Paulo

11h45 lunch/PosteR VieW

satellite syMPosiuM 3 – aBBott

13h00 confeRence 5

iodine and autoimmunity John Lazarus Cardiff (UK)

Chairs: Fernando Humberto Munizaga Castillo, Santiago Carmen Cabezón, Buenos Aires

14h00 syMPosiuM 7

thyroid autoimmunity Chairs: Claudia Riedel, Santiago Miriam da Costa Oliveira, Porto Alegre

1. Challenges in Graves’ disease treatment João Romaldini, Sao Paulo 2. The spectrum of subclinical hypothyroidism and autoimmunity Gabriela Brenta, Buenos Aires 3. Thyroid autoimmune impact on children Sonia Iorcansky, Buenos Aires4. Iodine excess and autoimmunity Geraldo Medeiros-Neto, Sao Paulo

Discussion






S141

14h00 syMPosiuM 8

tissue effect of thyroid hormones Chairs: Denise Pires de Carvalho, Rio de Janeiro María del Mar Montesinos, Córdoba

1. Thyroid hormone in male gonadal function Marcia Wagner, Porto Alegre 2. Thyroid function and reproduction Graciela Jahn, Mendoza 3. Thyroid hormone action at the endothelium John Lazarus, Cardiff (UK)4. Thyroid hormone and the immune system Claudia Pellizas, Córdoba

Discussion

Meet –the-eXPeRt 3

new treatment concepts in graves ophtalmopathy Walter Bloise, Sao Paulo

Chairs: Leandro Diehl, Londrina

15h30 coffee BReak/PosteR VieW

15h45 thyRoiD DeBate 2

Moderator: Valéria Guimarães, Brasília

1. Evidences that “high RAI exposure for differentiated thyroid cancer dose are not safe”

Rui M. B. Maciel, Sao Paulo 2. Evidences that “high RAI doses for differentiated thyroid cancer are safe

and effective” Marília Marone, Sao Paulo

thyRoiD DeBate 3

Moderator: Hans Graf, Curitiba

1. Subclinical hypothyroidism should be treated Mario Vaisman, Rio de Janeiro 2. Subclinical hypothyroidism should not be treated João Romaldini, Campinas






S142

15h45 Meet-the-eXPeRt 4

how to use thyroid ultrasound in a rational way Eduardo Tomimori, Sao Paulo

Chairs: Marcia Netto de Campos da Silva, Florianópolis Giuseppe Repetto, Porto Alegre

16h45 confeRence 5

thyroid hormone metabolism, from bench to bedside P. Reed Larsen, Boston (USA)

Chairs: Ana Luiza Maia, Porto Alegre Chady S. Farah, Sao Paulo

17h50 lats geneRal asseMBly

20h30 gala DinneR






S143

Sunday, May 3rd, 2009

8h00 confeRence 6

thyroid and pregnancy John Lazarus, Cardiff (UK)

Chair: Marcos S. Abalovich, Buenos Aires

9h00 oRal session 5

Basic Chairs: Egberto Gaspar de Moura, Rio de Janeiro Erika Laurini de Souza Meyer, Porto Alegre

oR. 17. Effects of proinflammatory cytokines on type 2 deiodinase in nonthyroid illness syndrome. Wajner SM, Goemann IM, Maia ALSetor de Tireoide, Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

oR. 18. Triiodothyronine stimulates dendritic cell function through a PI3K-independent AKT pathway crucial role of thyroid hormone receptor β1, a new NF-kB target gene. Mascanfroni I1, Montesinos MM1, Alamino VA1, Susperreguy S1, Nicola JP1, Masini-Repiso AM1, Rabinovich GA2, Pellizas CG1

1Centro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI, CONICET) Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina; 2Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, IBYME, CONICET y Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

oR. 19. Regulation of the thyroid dual oxidase activity by thyrotropin and iodine. Ferreira ACF, Freitas ML, Ginabreda MGP, Cardoso LC, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brazil

oR. 20. Triiodothyronine (T3) promotes the development of an antigen-specific cytotoxic response through modulation of dendritic cell (DC) function. Alamino VA, Mascanfroni ID, Montesinos MM, Susperreguy S, Masini-Repiso AM, Rabinovich GA, Pellizas CGCIBICI-CONICET, Depto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina



Scientific Program – Sunday, May 3nd, 2009

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9h00 oRal session 6

clinical Chairs: Gabriela Brenta, Buenos Aires Marisa Maria Dreyer Breitenbach, Rio de Janeiro

oR. 21. Eight new TPO mutations and high frequency of monoallelic mutations indicate genetic heterogeneity in patients with congenital hypothyroidism with total and/or partial iodide organification. Neves SC1, Dias V2, Viana M2, Chagas AJ2, Knobel M1, Medeiros-Neto G1, Rubio GS1

1Thyroid Unit (Lim25), University of Sao Paulo Medical School, Sao Paulo, Brazil; 2NUPAD, Medicine School of the University of Minas Gerais, Belo Horizonte, Brazil

oR. 22. Correlação entre a dosagem de iodo em urina de 24 horas e amostra isolada nos pacientes submetidos a tratamento com iodo radioativo. Padovani RP1-2, Marone MS2, Vieira JGH1, Maciel RMB1, Biscolla RPM1

1Disciplina de Endocrinologia, Universidade Federal de Sao Paulo; 2Serviço de Medicina Nuclear da Santa Casa de Misericórdia de Sao Paulo; Sao Paulo Brasil

oR. 23. Determinación de atpasas como opción para diagnostico de malignidad en nódulo tiroideo.Hurtado-Lopez LM1, Dominguez Fonseca CB1, Velazquez-Fernandez D2

1Clínica de tiroides Hospital General de México; 2Instituto Nacional de Medicina Genomica; México

oR. 24. Lack of association between subclinical hypothyroidism and emerging cardiovascular risk factors in a population-based study. the Japanese-Brazilian Thyroid Study. Sgarbi JA1-2, Matsumura L1, Kasamatsu T1, Maciel RMB1

1Laboratory of Molecular Endocrinology, Division of Endocrinology, Federal University of Sao Paulo; Sao Paulo, Brazil; 2Division of Endocrinology, Department of Medicine, Faculdade de Medicina de Marília; Marília, Brazil


10h15 syMPosiuM 9

special topics on thyroid and pregnancy Chairs: Silvia Gutierrez, Buenos Aires Luiza K. Matsumura, Sao Paulo

1. Screening of post partum thyroiditis, yes or not? John Lazarus, Cardiff (UK)2. Treatment of subclinical hypothyroidism during pregnancy and the

preconception period: optimal levels of TSH Marcos S. Abalovich, Buenos Aires 3. Maternal hypothyroxinemia impairs spatial learning and synaptic nature

and function in the offspring Claudia Riedel, Santiago de Chile4. Fetal repercussion of the treatment of maternal hyperthyroidism. Graciela Alcaraz, Buenos Aires

Discussion




S145

10h15 syMPosiuM 10

iodine deficiency and excess in the thyroid gland icciDD – international council for the control of iondine Deficiency Disorders Chair: Gerard Burrow, USA – Chairman of the ICCIDD

1. Requirement of iodine in pregnant and lactating women Michael Zimmermann, Zurich, Editor of IDDNewsletter, ICCIDD 2. Impact of iodine excess intake Meyer Knobel, Sao Paulo 3. How to secure the elimination of iodine deficiency avoiding iodine

excess in Latinamerica Eduardo Pretell, Lima – Regional Coordinator for America, ICCIDD

Meet-the-eXPeRt 5

lymph node metastases: correlation among fna cytology, thyroglobulin in the needle wash and us findings Rosa Paula Biscolla, Sao Paulo

Chairs: Ana Orlandi, Buenos Aires Liliana Bergoglio, Córdoba

11h45 lunch/PosteR VieW

13h00 confeRence 7

the thyroid, age and the heart Ulla Feldt-Rasmussen, Kopenhagen

Chairs: José Agusto Sgarbi, Marília Adriana Reyes, Buenos Aires

14h00 syMPosiuM 11

thyroid diseases in children Chairs: Hector M. Targovnik, Buenos Aires Sonia Iorcanski, Buenos Aires

1. Genetic basis of congenital hypothyroidism Ileana Rubio, Sao Paulo 2. rhTSH in the diagnostic and treatment of pediatric thyroid cancer Viviana Hersovich, Buenos Aires 3. Graves’ disease in the pediatric population Osmar Monte, Sao Paulo 4. Congenital hypothyroidism screening, a successful program at the State

of Parana, Brazil Rosana Marques Pereira, Curitiba






S146

14h00 syMPosiuM 12

thyroid and nutrition Chairs: Alicia Lowenstein, Buenos Aires Maria Cristina Belzarena, Montevideo

1. Neonatal programming of neuroimmunomodulation: role of adipocytokines and neuropeptides

Egberto Gaspar de Moura, Rio de Janeiro 2. The role of TNF a in the control of food intake and energy expenditure

in Obesity Ana Paula Souza Arruda, Rio de Janeiro 3. Food restriction, body protein loss and thyroxine use Denise Pires de Carvalho, Rio de Janeiro

Meet-the-eXPeRt 6

What is new in medullary thyroid cancer? Nelson Wohllk, Santiago

Chairs: Eduardo Pusiol, Mendoza Marcia Khaled Puñales, Porto Alegre


15h45 syMPosiuM 13

hot topics in thyroidology Chairs: Diana L. Kleiman de Pisarev, Buenos Aires Fabiola I. Miasaki, Curitiba

1. Thyrosine kinase inhibitor and the RECIST criteria in clinical trials Paulo Marcelo Gehm Hoff, Sao Paulo 2. Impact of the last published trials with thyroid cancer target-drugs Cléo Otaviano Mesa Junior, Curitiba 3. Thyroid disruptors Laura Ward, Campinas

thyRoiD DeBate

Micropapillary thyroid cancer Moderator: José Luis Novelli, Rosario

It is an incidental finding and should not be treatedClaudio G. Liberman, Santiago de ChileIt is a true disease and should be treatedNilton Tabajara Herter – Porto Alegre






S147

15h45 PosteR DeBate

thyroid hormone metabolism and action Chairs: Doris Rosenthal, Rio de Janeiro Ana Maria Masini-Repiso, Córdoba

Po. 031. Interaction of type 2 iodothyronine deiodinase THR92ALA and peroxissome proliferactor-activated receptor gama-2 Pro12Ala polymorphisms in the modulation of insulin resistance. Estivalet AAF, Leiria LB, Canani LH, Maia AL, Crispim DEndocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Porto Alegre, Brazil

Po. 038. Thyroid cells up-regulate toll-like receptor 4 expression and pro-inflammatory mediators in response to LPS stimulation: new players in the innate immune response?Nicola JP, Gatti G, Maccioni M, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología. CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

Po. 044. Iodotironinas desiodases são reguladas pela administração crônica de 3,5-diiodotironina. Padrón AS, Pantaleão TU, Andrade BM, Araújo RL, Carvalho DPLaboratório de Fisiologia Endócrina, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

Po. 045. Efeito da restrição alimentar e da administração de triiodotironina (T3) sobre a morfometria cardíaca em ratos obesos. Marino J, Luvizotto RAM, Nascimento AF, De Sibio MT, Almeida NCP, Olimpio RMC, Nogueira CRLaboratório Experimental de Clínica Médica, Faculdade de Medicina Botucatu, Unesp; Botucatu, Brasil

Po. 050. A case study of the thyroid hormone receptor alpha homodimer interface. Ribeiro ICJ1, De Farias RF1, Bampa G1, Neves FAR1, Polikarpov I2, Togashi M1

1Department of Pharmaceutical Sciences, Health Sciences School, University of Brasilia; Brasilia, Brazil; 2Department de Physics and Informatics, São Carlos Physic Institute, University of Sao Paulo; Sao Paulo, Brazil

Po. 052. Acute T3 administration reduces polyadenylation of βTSH mRNA of hypothyroid rats: a non genomic action of thyroid hormone. Souza PB, Bruneto EL, Nunes MTLaboratory of Endocrine Physiology, Department of Physiology and Biophysics, Institute of Biomedical Science (ICB), University of Sao Paulo; Sao Paulo, Brazil

Po. 053. Efeito do hormônio tireoideano sobre o conteúdo e translocação do transportador de glicose GLUT4 no tecido adiposo: possível ação não-genômica do hormônio. Croffi RV, Teixeira SS, Machado UF, Nunes MTLaboratório de Fisiologia Endócrina, Depto. de Fisiologia e Biofísica, ICB, USP; São Paulo, Brasil

Po. 059. Substitution of serine for proline in the active center of type 2 iodothyronine deiodinase substantially alters its in vitro biochemical properties but not its function in vitro. Goemann IM1, Harney JW2, Maia AL1, Larsen PR2

1Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Porto Alegre, Brazil; 2Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School Boston; Massachussetts, USA.

Po. 060. O iodo altera a expressão do mRNA de pendrina: estudo in vitro e in vivo. Calil-Silveira J, Serrano-Nascimento C, Nunes MTDepartamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de Sao Paulo; São Paulo, Brasil



S148

Po. 135. An altered expression of CCR3, CCR7 and CXCR4 in papillary thyroid cancer. González HE1, Leiva A4, Tobar H3, Böhmwald K4, Tapia K1, Kalergis AM2-3, Riedel CA4

¹Departamento de Cirugía Oncológica y ²Reumatología, Facultad de Medicina Pontificia Universidad Católica de Chile. ³Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile. 4Laboratorio de Biología Celular y Farmacología, Departamento de Ciencias Biológicas, Facultad de la Salud, Universidad Andrés Bello.

16h50 aDjouRn, MeRck young inVestigatoR PRize WinneRs – Basic anD clinical

17h00 haPPy-PosteR session Wine anD cheese RecePtion



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satellite symPosia

Friday, May 1st, 2009

11h50 MeRck seRono

interacting with subclinical hypothyroidism: sharing experiences interectuando con el hipotiroidismo subclínico: compartiendo experiencias interagindo com hipotiroidismo subclínico: dividindo experiências Moderador: Hans Graf, Curitiba

Debatedores: Gabriela Brenta, Buenos Aires Mario Vaisman, Rio de Janeiro Nelson Wohllk, Santiago

18h00 genzyMe

thyroid cancer – update and new treatment evidences update on ablation of thyroid remnants Fabian Pitóia, Buenos Aires

new evidences on target therapy Hans Graf, Curitiba

Discussion

Saturday, May, 2nd, 2009

11h50 aBBott

Doença tireoidiana mínima e hemodinâmica no exercício impacto do hipotiroidismo subclínico na resposta cardiovascular em exercício e repouso Mário Vaisman, Rio de Janeiro

aplicabilidade do teste cardiopulmonar e ergométrico na avaliação de risco do paciente com doença tiroidiana mínima Almir Sérgio Ferraz, Sao Paulo




S150

Adriana Reyes, MDDivisión Endocrinología, Hospital José Maria Ramos MejíaBuenos Aires, Argentina. [email protected] Disclosure: None

Alberto Rossetti FerrazDepartamento de Cirurgia, Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: Not Informed

Alexandre Buescu Universidade Federal do Rio de Janeiro, RJ, Brasil. [email protected]: None

Alfio J. Tincani Departamento de Cirurgia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas. Campinas, SP, Brasil. [email protected]: None

Alicia Gauna División Endocrinología, Hospital José Maria Ramos MejíaBuenos Aires, Argentina. [email protected] Disclosure: None

Alicia Lowenstein División de Endocrinologia, Hospital José Maria Ramos MejíaBuenos Aires, Argentina. [email protected] Disclosure: Not Informed

Ana Beatriz Pinotti MiklosHospital Servidor Público Estadual e Faculdade de Medicina – ABC. São Paulo, Brasil. [email protected] Disclosure: None

Ana Luiza Maia Setor de Tireoide, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil. [email protected]: None

Ana Maria Masini-Repiso Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Córdoba, Argentina. [email protected] Disclosure: Not Informed

sPeaKers, cHairs & moderators

Ana Maria Orlandi Faculdad de Medicina, Universidad de Buenos Aires. Buenos Aires, Argentina. [email protected] Disclosure: None

Ana O. Hoff Department Medical Specialties-Endocrinology, University of Texas MD Anderson Cancer Center; Medical Advisor in Endocrinology, Fleury Research Institute, São Paulo, Brazil [email protected] Disclosure: None

Ana Paula Souza Arruda Post-doc fellow from the Lab of Cellular Signaling, School of Medical Sciences, Universidade Federal de Campinas, Campinas, SP, Brasil. [email protected]: None

Antonio José Gonçalves Departamento de Cirurgia, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, SP, Brasil. [email protected]: Not Informed

Carlos Neutzling Lehn Serviço de Cirurgia de Cabeça e Pescoço, Hospital Heliopólis, São Paulo, SP, Brasil. [email protected]: None

Carmem Cabanelas Pazos de Moura Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. [email protected]: None

Carmen Cabezón Hospital Italiano de Buenos Aires, Buenos Aires, Argentina. [email protected]: None

Celso Friguglietti Serviço de Cirurgia de Cabeça e Pescoço, Faculdade de Medicina da Universidade de Santo Amaro (FMUNISA), São Paulo, SP, [email protected] Disclosure: Not Informed

Chady Satt Farah Laboratório de Doenças da Tiroide, Endocrinologia, Hospital do Servidor Público EstadualSão Paulo, SP, [email protected]: Not Informed

Claudia Gabriela Pellizas Departamento de Bioquímica Clínica Facultad de Ciências Químicas, Universidad Nacional de Córdoba, Córdoba, [email protected] Disclosure: Not Informed

Claudia Riedel Laboratorio de Biología Celular y Farmacología, Departamento de Ciencias Biológicas, Universidad Nacional Andrés Bello, Santiago, Chile. [email protected]: None

Claudio Cordeiro Albino Instituto de Endocrinologia e Diabetes de Maringá, Maringá, PR, Brasil. [email protected] Disclosure: Not Informed

Claudio Liberman G. Sección de Endocrinologia, Hospital Clinico, Universidad de Chile, Santiago, [email protected]: None

Claudio Roberto Cernea Serviço de Cabeça e Pescoço, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected]: None

Cláudio Rogério Alves de Lima Cirurgia de Cabeça e Pescoço, Hospital São Rafael, Salvador, BA, [email protected] Disclosure: Not Informed

Cleo Otaviano Mesa Júnior Serviço de Endocrinologia e Metabologia do Paraná (SEMPR), Hospital de Clínicas, Universidade Federal do Paraná (UFPR). Curitiba, PR, [email protected]: None

Daniel SperbIrmandade da Santa Casa de Misericórdia de Porto Alegre, Hospital Santa Rita.Porto Alegre, RS, Brasil. [email protected]: Not Informed

Denise Pires de Carvalho Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ)Rio de Janeiro, RJ, Brasil. [email protected]: Editorial board involvement (Endocrinology)

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Diana L. Kleiman de Pisarev Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, [email protected]: None

Doris Rosenthal Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ)Rio de Janeiro, RJ, Brasil. [email protected]: None

Edna T. Kimura Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: Editor-in-Chief, Arquivos Brasileiros de Endocrinologia & Metabologia.

Eduardo Néstor Faure – Buenos Aires Sección de Tiroides, Servicio de Endocrinología, Hospital Churruca-Visca. Buenos Aires, Argentina. [email protected]: Not Informed

Eduardo A. PretellConsejo Internacional para El Control de Los Desordenes por Deficiencia de Yodo, Universidad Peruana, Lima, Peru. [email protected]: Not Informed

Eduardo Pusiol Instituto de Patología Tiroidea, Facultad de Ciencias Médicas, Universidad de Cuyo Mendoza, Argentina. [email protected] Disclosure: Not Informed

Eduardo Kiyoshi Tomimori Unidade de Tiroide, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected]: None

Egberto Gaspar de Moura Departamento de Ciências Fisiológicas, Instituto de Biología Roberto Alcântera Gomes, Universidade do Estado do Rio de Janeiro (UERJ)Rio de Janeiro, RJ, Brasil. [email protected] Disclosure: None

Erika Laurini de Souza MeyerSetor de Tireoide, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil. [email protected]: None

Erivelto Martinho Volpi Cirurgia Cabeça e Pescoço, Hospital das Clínicas, Universidade de São PauloSão Bernardo Campo, SP, Brasil. [email protected]: Not Informed

Evandro Cezar Guerreiro de VasconcelosClínica Privada, Cirurgia Cabeça e Pescoço, Curitiba, PR, [email protected]: Not Informed

Fabián Pitoia División de Endocrinología, Hospital de Clínicas José de San Martin, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. [email protected] Disclosure: Consultant/Speaker Bureau: Genzyme

Fabiola Yukiko Miasaki Serviço de Endocrinologia e Metabolismo do Paraná (SEMPR), Universidade Federal do Paraná, Curitiba, PR, Brasil. [email protected]: None

Fernando Humberto Munizaga Castillo Departamento de Medicina, Unidad Endocrinologia, Universidad de Chile Campus Central y Hospital Clinico San Borja, Arriarán, Santiago, Chile. [email protected]: Not Informed

Fernando Luiz Dias Instituto Nacional do Cancer, Pontifícia Universidade Católica do Rio de Janeiro (PUC-RJ), Rio de Janeiro, RJ, [email protected]: None

Flávio Carneiro Hojaij Hospitais Nove de Julho, São Camilo, Metropolitano e Santa Helena, Médico Assistente do SCCP da Escola Paulista de Medicina, São Paulo, SP, [email protected]: None

Flavio Zelmanovitz Serviço de Medicina Nuclear, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil. [email protected] Disclosure: None

Francisco de Assis Rocha Neves Departamento de Farmacologia, Faculdade de Ciências da Saúde, Universidade de Brasília,Brasília, DF, Brasil. [email protected]: Not Informed

Gabriela Brenta Departamento de Endrocinología y Metabología, Hospital Francés, Buenos Aires, Argentina. [email protected] Disclosure: Consultant/Speaker Bureau: Merck

Gerard Burrow International Council for the Control of Iondine Deficiency Disorders (ICCIDD), John Hopkins Hospital, Baltimore, [email protected]; [email protected]: None

Geraldo Medeiros-Neto Laboratório Molecular de Tiroide, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo (USP), São Paulo, SP, [email protected]: Not Informed

Gilberto Vaz Teixeira Centro de Pesquisas Oncológicas (CEPON), Florianópolis, SC, Brasil. [email protected]: Not Informed

Gisah Amaral de Carvalho Serviço de Endocrinologia e Metabologia do Paraná (SEMPR), Setor de Ciências da Saúde, Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Paraná (UFPR), Curitiba, PR, [email protected]: None

Giuseppe Repetto Serviço de Endocrinologia do Hospital São Lucas, Faculdade de Medicina, Departamento de Medicina Interna, Pontifícia Universidade Católica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS, [email protected]: Not Informed

Graciela Alcaraz División Endocrinología del Hospital Carlos G. Durand, Buenos Aires, Argentina. [email protected] Disclosure: Not Informed

Graciela Alma Jahn Laboratorio de Reproducción y Lactancia (LARLAC), Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), Consejo Nacional de Investigaciones Científicas y Técnicas de la Argentina (CONICET), Buenos Aires, Argentina. [email protected] Disclosure: None

Speakers, chairs & moderators

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Gregory Randolph Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USA. [email protected] Disclosure: None

Guillermo Juvenal División de Bioquímica Nuclear, Comisión Nacional de Energia Atômica, Buenos Aires, Argentina. [email protected]: None

Gustavo Caldas Departamento de Endocrinologia, Unidade de Diabetes e Endocrinologia, Recife, PE, Brasil. [email protected] Disclosure: Not Informed

Hans Graf Serviço de Endocrinologia e Metabologia do Paraná (SEMPR), Setor de Ciências da Saúde, Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brasil. [email protected]: Grant/Research Support – Genzyme, IncConsultant/Speaker Bureau – Merck Serono

Hector M. Targovnik Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET), Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. [email protected]: Not Informed

Henning Dralle Department of General, Visceral and Vascular Surgery, Medical Faculty, University of Halle-Wittenberg, Halle, Germany [email protected]: Honorarium recipient – Medtronic

Hugo Niepomniszcze Departamento de Bioquímica Clínica, Hospital Clínico, Universidad de Buenos Aires Buenos Aires, Argentina. [email protected]: Not Informed

Igor Polikarpov Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos, SP, Brasil. [email protected] Disclosure: Not Informed

Ileana Rubió Unidade de Tireoide, Serviço de Endocrinologia, Faculdade de Medicina, Universidade São Paulo (USP), São Paulo, SP, Brasil. [email protected]: None

Janete M. Cerutti Departamento de Morfologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brasil. [email protected]: None

João Hamilton Romaldini Laboratório de Doenças da Tiroide, Serviço de Endocrinologia, Hospital do Servidor Público Estadual e Faculdade de Ciências Médicas, Pontifícia Universidade Católica de Campinas (PUC Campinas), Campinas, SP, [email protected]: None

John Lazarus Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff University Cardiff, UK. [email protected]: Grants/Research Support – Welcome TrustEditorial Board Involvement – Journal of Clinical Endocrinology & Metabolism

Jorge A.Jara Yorg Universidad Nacional de Asunción, Asunción, Paraguay. [email protected]: None

Jorge Pinho Hospital Memorial São José, Recife, PE, Brasil. [email protected] Disclosure: None

José Augusto Sgarbi Departamento de Endocrinologia, Faculdade Médica de Marília, Marília, SP, Brasil. [email protected]: None

José Francisco de Góis Filho Serviço de Cirurgia de Cabeça e Pescoço Instituto do Câncer Arnaldo Vieira de Carvalho da Santa Casa de São Paulo, São Paulo, SP, [email protected] Disclosure: Not Informed

José Higino Steck Serviço de Cirurgia de Cabeça e Pescoço, Hospital Municipal de Campinas, Campinas, SP, Brasil. [email protected]: None

José Luis Novelli Universidad Nacional de Rosario, Facultad de Ciencias Medicas, Rosario, [email protected] Disclosure: Not Informed

Laura Sterian Ward Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brasil. [email protected] Disclosure: None

Léa Maria Zanini MacielDivisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. [email protected] Disclosure: None

Lenine Garcia Brandão Departamento de Cirurgia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, [email protected]: Not Informed

Leandro Arthur Diehl Universidade Estadual de Londrina, Centro de Ciências da Saúde, Departamento de Clínica Médica, Londrina, PR, Brasil [email protected]; [email protected] Disclosure: Financial Material Support: Travel Grants from Sanofi Aventis and Pfizer.

Liliana Maria BergoglioServicio de Endocrinología, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina. Córdoba, [email protected] Disclosure: None

Luis Soto Díaz Servicio de Endocrinología, Hospital DIPRECA, Santiago, Chile. [email protected] Disclosure: None

Luiz Paulo Kowalski Departamento de Cirurgia de Cabeça e Pescoço, Hospital do Câncer de São Paulo e Fundação A.C. Camargo, São Paulo, SP, Brasil. [email protected] Disclosure: None

Luiza K. Matsumura Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brasil. [email protected] Disclosure: Not Informed

Marcia K. C. PuñalesSetor de Tireoide, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre Universidade Federal do Rio Grande do Sul e Instituto da Criança com Diabetes, Grupo Hospitalar Conceição (GHC), Porto Alegre, RS, Brasil. [email protected]: None


S153

Marcia Netto de Campos da Silva Universidade do Sul de Santa Catarina (UNISUL) e Unidade da Tireoide, Hospital Geral São José, Florianópolis, SC, Brasil. [email protected]: None

Márcia Santos Wagner Setor de Tireoide, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil. [email protected]: None

Marcio Abrahão Serviço de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brasil. [email protected] Disclosure: Not Informed

Marco Kulcsar Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: None

Marcos Brasilino de Carvalho Hospital Heliopolis, São Paulo, SP, Brasil. [email protected] Disclosure: None

Marcos Abalovich División de Endocrinologia, Hospital Carlos G. Durand, Buenos Aires, Argentina. [email protected] Disclosure: Not Informed

Maria Cristina BelzarenaFacultad de Medicina de la Universidad de la República, Montevideo, [email protected] Disclosure: None

María del Mar Montesinos Departamento de Bioquímica, Facultad de Ciências Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. [email protected]: Not Informed

Maria Tereza Nunes Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: None

Marília Marone Sociedade Brasileira de Biologia e Nuclear da Santa de Misericórdia de São Paulo, São Paulo, SP, [email protected] Disclosure: Not Informed

Mario Pisarev Departamento de Radiobiologia, Comisión Nacional de Energía AtómicaBuenos Aires, Argentina. [email protected] Disclosure: Not Informed

Mario Vaisman Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, [email protected] Disclosure: Consultant/Speaker Bureau: Abbott, Merck, Sanofi Aventis, Genzyme.

Marisa Maria Dreyer Breitenbach Instituto Nacional de Câncer, Ministério da Saúde, Rio de Janeiro, Brasil. [email protected] Disclosure: None

Marta A. Schnitman Departamento de Endocrinología y Metabologia, Hospital Francés, Buenos Aires, Argentina. [email protected] Disclosure: None

Meyer Knobel Unidade de Tireoide, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: None

Michael Zimmermann Swiss Federal Institute of Technology, Zurich, Switzerland [email protected]: Not Informed

Miriam da Costa Oliveira Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA)Porto Alegre, RS, Brasil. [email protected]: None

Nelson WohllkDepartamento de Endocrinología, Hospital del Salvador, Facultad de Medicina, Universidad de Chile, Santiago, Chile. [email protected] Disclosure: Advisory Board Membership: Genzyme.Honorarium Recipient: Merck Quimica.

Nilton Herter Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) Porto Alegre, RS, Brasil. [email protected] Disclosure: None

Onivaldo CervantesUniversidade Federal de São Paulo (USP), São Paulo, SP, Brasil. [email protected]: Not Informed

Osmar Monte Departamento de Medicina, Faculdade de Ciências Médicas Santa Casa de São PauloSão Paulo, SP, Brasil. [email protected] Disclosure: Advisory Board Membership: Novartis

Paulo Marcelo Gehm HoffCentro de Estudos Clínicos de Câncer, Hospital Albert Einstein e Universidade de São Paulo, São Paulo, SP, Brasil. [email protected]: None

Ralf Paschke Third Medical Department, University of Leipzig, Leipzig, Germany. [email protected]: None

P. Reed Larsen Thyroid Division, Brigham and Women Hospital Boston, Harvard Medical School, Boston, MA, USA. [email protected]: None

Richard T.Kloos The Ohio State University, Columbus, OH, [email protected]: Grant/Research Support: Genzyme, VeracyteAdvisory Board Membership: Genzyme, Veracyte, Bayer, OnixEditorial Board Involvement: Journal of Clinical Endocrinology & MetabolismOther Financial Material Support: ATA Secretary, Chief operating office.

Roberto Araújo Lima M.D. Pontifícia Universidade Católica do Rio de Janeiro, Rio de Janeiro, RJ, Brasil. [email protected] Disclosure: None

Rogério Dedivitis Santa Casa de Misericórdia de Santos e Fundação Lusíada, Centro Universitário Lusíada, Universidade Metropolitana de Santos, Santos, SP, Brasil. [email protected] Disclosure: None

Rosa Paula Biscolla Divisão de Endocrinologia da Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp), São Paulo, SP, Brasil. [email protected] Disclosure: Not Informed


S154

Rosalinda Asato Camargo Unidade de Tireoide, Serviço de Endocrinologia, Universidade de São Paulo. São Paulo, SP, [email protected] Disclosure: Not Informed

Rosana Marques Pereira Unidade Endocrinologia Pediátrica (UEP), Setor de Ciências da Saúde, Hospital de Clínicas, Universidade Federal do Paraná (UFPR), Curitiba, PR, Brasil. [email protected] Disclosure: None

Rui M.B. Maciel Laboratório de Endocrinologia Molecular, Departamento de Medicina, Escola Paulista de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: None

Silvia Gutierrez Human Reproduction and Thyroid Sections Endocrinology Division, Hospital Carlos Durand.Buenos Aires, Argentina. [email protected] Disclosure: Not Informed

Sonia Iorcansky Laboratório de Pesquisa de Enfermedades Congénitas, Hospital de Pediatría Dr. Juan P. Garrahan, Buenos Aires, [email protected] Disclosure: Not Informed

Tania M. Ortiga-Carvalho Instituto de Biofísica, Laboratório de Fisiologia Endócrina, Universidade Federal do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brasil. [email protected] Disclosure: None

Thomas S. Scanlan Department of Physiology and Pharmacology, Oregon Health and Science UniversityPortland, Oregon, [email protected]: Editorial Board Involvement: Thyroid

Ulla Feldt-Rasmussen Department of Endocrinology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. [email protected]: None

Valéria GuimarãesBrasília, DF, Brasil. [email protected] Disclosure: None

Vânia Maria Corrêa da Costa Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UERJ)Rio de Janeiro, RJ, Brasil. [email protected] Disclosure: None

Vergilius José Furtado de Araújo Filho Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected] Disclosure: None

Viviana Clara Herzovich Laboratório de Pesquisa de Endócrino, Hospital Nacional de Pediatria Juan P. Garrahan Buenos Aires, Argentina. [email protected] Disclosure: Not Informed

Walter Bloise Departamento de Clínica Médica, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brasil. [email protected]: None


abstracts – oral Presentation

S156

or. 01 Smurfs, TGFβ pathway regulation ubiquitin ligases, are highly expressed in papillary thyroid carcinoma .............S157 Fiore APZP, Raimundo SG, Ricarte-Filho JCM, Kimura ET

or. 02 Efeito do tratamento agudo com iodeto e perclorato na expressão, comprimento da cauda poli-A e tradução do mRNA do cotransportador de sódio-iodeto (NIS) em ratos e células PCCl3 ...................................S157 Serrano-Nascimento C, Goulart-Silva F, Nunes MT

or. 03 The oncogene BRAFT1799A increased Notch 1 expression in thyroid cell line and in transgenic mice ..................S157 Yamashita AS, Rezende E, Fuziwara C, Gonçalves SR, Kimura ET

or. 04 Intestinal NA+/I- symporter (NIS) expression is regulated at post-transcriptional level by high concentrations of iodide ................................................................................................................................................................................S158 Nicola JP, Susperreguy S, Carrasco N, Masini-Repiso AM

or. 05 The role of ret genetic variants in hereditary medullary thyroid carcinoma ..............................................................S158 Siqueira DR, Rocha AP, Meotti C, Estivalet A, Puñales MK, Maia AL.

or. 06 NIS mRNA levels are lower in papillary thyroid carcinomas but do not correlate with nis protein localization in the neoplastic follicular cells .....................................................................................................................S158 Morari EC, Marcello MA, Cunha LL, Guilhen ACT, Vassallo J, Soares FA, Ward LS

or. 07 Percutaneous ethanol injection treatment of cervical lymph node metastases of papillary thyroid cancer ........S159 Perez CLS, Mesa Jr C, Trippia M, Carvalho GA, Graf H

or. 08 Nuclear chromatin texture transformation may be related to the expression of genes involved in tumor progression and help identify papillary thyroid carcinomas with aggressive behavior ...........................................S159 Ferreira RC, Morari EC, Silva JR, Guilhen ACT, Adam RL, Leite NJ, Matos PS, Assumpção LM, Vassalo J, Soares F, Metze K, Ward LS

or. 09 Novel involvement of NFkB subunit P65 in the lipopolysaccharide-induced NA+/I- symporter gene expression ..S159 Nicola JP, Nazar M, Mascanfroni I, Masini-Repiso AM

or. 10 Evidência de ação não genômica do hormônio tireoidiano (HT) no controle da expressão gênica e proteica do transportador de glicose glut4 em células 3T3-L1 (adipócitos) ...............................................................S160 Teixeira SS, Serrano-Nascimento C, Poyares LL, Machado UF, Nunes MT

or. 11 Diferenças tecido-específicas na regulação da expressão da glutationa S-transferase por hormônios tireoi deanos ..........................................................................................................................................................................S160 Faustino LC, Pires RM, Lima AC, Carvalho TMO

or. 12 Estrogen increases thyroid hydrogen peroxide generation by dual oxidase in female rats ....................................S160 Ferreira ACF, Pantaleão TU, Freitas ML, Ginabreda MGP, Cardoso LC, Costa VMC, Carvalho DP

or. 13 A novel syndrome related to selenoproteins deficiency ................................................................................................S161 Azevedo MF, Barra GB, Castro LC, Amato AA, Velasco LFR, Godoy P, Naves LA, Neves FAR

or. 14 Effects of pentoxifylline, nicotinamide/allopurinol and methylprednisolone in the proptosis and inflammatory markers in patients with Graves’ ophthalmopathy (GO) .......................................................................S161 Fernandes LPS, Cruz JB, Pivotto DR, Jorge EN, Padovani CR, Nogueira CR, Mazeto GMFS

or. 15 CTLA-4 318 polimorphisms are a factor of risk for Graves’ ophthalmopathy in Brazilian patients .............................S161 Bufalo NE, Santos RB, Leite JL, Guilhem MS, Silva ACN, Romaldini JH, Ward LS

or. 16 Herpesvirus type 7 infection is a factor of risk for Graves’ disease in Brazilian but not in dutch patients .................S162 Leite JL, Bufalo NE, Santos RB, Vos XG, Romaldini JH, Wiersinga WM, Ward LS

or. 17 Effects of proinflammatory cytokines on type 2 deiodinase in nonthyroid illness syndrome ....................................S162 Wajner SM, Goemann IM, Maia AL

or. 18 Triiodothyronine stimulates dendritic cell function through a PI3K-independent AKT pathway crucial role of thyroid hormone receptor β1, a new NF-kB target gene ............................................................................................S162 Mascanfroni I, Montesinos MM, Alamino VA, Susperreguy S, Nicola JP, Masini-Repiso AM, Rabinovich GA, Pellizas CG

or. 19 Regulation of the thyroid dual oxidase activity by thyrotropin and iodine ..................................................................S163 Ferreira ACF, Freitas ML, Ginabreda MGP, Cardoso LC, Carvalho DP

or. 20 Triiodothyronine (T3) promotes the development of an antigen-specific cytotoxic response through modulation of dendritic cell (DC) function ......................................................................................................................S163 Alamino VA, Mascanfroni ID, Montesinos MM, Susperreguy S, Masini-Repiso AM, Rabinovich GA, Pellizas CG

or. 21 Eight new TPO mutations and high frequency of monoallelic mutations indicate genetic heterogeneity in patients with congenital hypothyroidism with total and/or partial iodide organification .....................................S163 Neves SC, Dias V, Viana M, Chagas AJ, Knobel M, Medeiros-Neto G, Rubio GS

or. 22 Correlação entre a dosagem de iodo em urina de 24 horas e amostra isolada nos pacientes submetidos a tratamento com iodo radioativo ...................................................................................................................................S164 Padovani RP, Marone MS, Vieira JGH, Maciel RMB, Biscolla RPM

or. 23 Determinación de atpasas como opción para diagnostico de malignidad en nódulo tiroideo ..........................S164 Hurtado-Lopez LM, Dominguez Fonseca CB, Velazquez-Fernandez D

or. 24 Lack of association between subclinical hypothyroidism and emerging cardiovascular risk factors in a population-based study the Japanese-Brazilian Thyroid Study ..................................................................................S164 Sgarbi JA, Matsumura L, Kasamatsu T, Maciel RMB

Abstracts – oral presentation – index

S157

OR. 01

Smurfs, TGFβ pathway regulation ubiquitin ligases, are highly expressed in papillary thyroid carcinoma

Fiore APZP, Raimundo SG, Ricarte-Filho JCM, Kimura ETCell & Developmental Biology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

The escape of the TGFβ antimitogenic effect is reported in several types of cancers. TGFβ pathway is negatively controlled by the Smad7 and Smurfs. Smurfs are E3 ligase proteins related to the Smads ubiquitin-mediated degradation process. The aim of this study was to observe the role of Smurf1 and Smurf2 in thyroid tumors and in RET/PTC3 oncogene activated thyroid cells. We have grown PTC3-5 cells, which are PCCl3 cells with inducible RET/PTC3. The mRNA and protein expression of Smurf1 and Smurf2 were evaluated by quantitative RT-PCR and Western blotting, respectively. The Smurf1 and Smurf2 expression were analyzed in human thyroid tissue samples, MNG (n = 20), FA (n = 8), PTC (n = 28), ATC (n = 5), FTC (n = 8), Normal (n = 6) and in rat methimazole induced goiter (n = 15), by immunohistochemistry. We observed that RET/PTC3 induced cells presented an increment in Smurf1 (24h: + 64%; 48h: + 76%; 72h: + 85%) and Smurf2 expression (24h: + 75%; 48h: + 42%; 72h: + 87%), a similar result was observed in both protein expression. The immunostaining revealed a higher expression of Smurf1 and Smurf2 in PTC, while fainted in MNG, FA, ATC and FTC. Moreover, rat pharmacological goiter did not presented any difference in Smurf1 nor Smurf2 expression when compared to normal rat thyroid tissue Conclusion: In this study we show the enhancement of negative regulatory factors of TGFβ signaling, such as Smurf1, Smurf2, in papillary thyroid carcinomas; however, the Smurfs were not modulated in thyroid hypertrophy. These data suggest that Smurfs are related to the thyroid oncogene activation and PTC development. Financial support: Capes, Fapesp, CNPq.

OR. 02

Efeito do tratamento agudo com iodeto e perclorato na expressão, comprimento da cauda poli-A e tradução do mRNA do cotransportador de sódio-iodeto (NIS) em ratos e células PCCl3

Serrano-Nascimento C, Goulart-Silva F, Nunes MTDepartment of Physiology and Biophysics, University of São Paulo, São Paulo, Brazil

Background: Iodide is an important regulator of thyroid activity, and its acute administration, in high dose, leads to the Wolff-Chaikoff effect. In this condition it is also detected a dowregulation of NIS expression/activity, which has been primarily related to TSH reduction, TGF-beta increase or iodolipids production. objectives: This study aimed to investigate if the acute iodide administration could modify the expression, poly-A tail length and translation of NIS mRNA, and if perchlorate treatment could interfere with iodide effects. Methods: MMI-treated rats and PCCl3 cells were treated with NaI (2 mg/0.5 ml saline ip, or 10-3 M, respectively), NaI + NaClO4 (equal doses) or saline, for 30 min up to 24h. NIS mRNA expression was evaluated by Northern Blotting (in vivo) or Real Time PCR (in vitro). NIS mRNA poly-A tail length, which is related to transcript stability, was determined by RACE-PAT. NIS mRNA translation rate was evaluated by means of PCCl3 cells Polysomal Profile. Results: Iodide treatment reduced the expression and poly-A tail length of NIS mRNA, in all period of time studied, in both experimental models, and perchlorate treatment reverted these effects. Iodide treatment also reduced NIS mRNA recruitment to polysome in PCCl3 cells. No changes in TSH were detected in serum or culture medium between experimental and control groups. The present data show that iodide per se decreases NIS mRNA expression, stability and translation by post-transcriptional mechanisms, adding new points to be considered on the molecular mechanisms that underlie the suppression of thyroid activity induced by iodide excess.Fapesp.

OR. 03

The oncogene BRAFT1799A increased Notch 1 expression in thyroid cell line and in transgenic mice

Yamashita AS, Rezende E, Fuziwara C, Gonçalves SR, Kimura ETDepartment of Cell Biology and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

The BRAFT1799A mutation is the most prevalent genetic alteration in papillary thyroid cancer, activating MAPK signaling constitutively. The effect of this induction in other signaling pathways remains unclear; however, there are mentions that MAPK can activate Notch pathway in head neck squamous cell carcinoma. The aim of the study was to evaluate the influence of BRAF T1799A oncogene in Notch pathway and thyroid differentiation. We constructed the PCCl3 harborings a doxycycline-inducible BRAFT1799A (PCCl3-BRAF), in which were evaluated the cell growth, gene expression of Notch1, Tsh receptor (Tshr), Na + -I-symporter (Nis), thyroglobulin (Tg) by quantitative RT-PCR and Notch1 protein expression by Western Blotting. The Notch1 protein expression in the transgenic mice target BRAFT1799A thyroid was evaluated by immunohistochemistry. PCCl3-BRAF after doxycycline treatment showed high Notch1 gene expression soon after 24h: + 130%, 48h: + 260% and 72h: + 56%. Moreover, Notch1 protein expression presented high expression 72 hours. On the other hand, the cell growth and gene expression of Tshr (-61.3%), Nis (-68.7%) and Tg (-55.7%) decreased after 72 hours. Furthermore, in the BRAFT1799A transgenic mice thyroid, Notch1 protein expression was also increased when compared with control group. Conclusion: thyroid cells expressing BRAFT1799A increased Notch1 expression in vitro and in vivo models and decreased the mRNA levels of genes related with thyroid differentiation, suggesting an important cross-talk participation in thyroid oncogenesis. Financial support: CNPq, Capes, Fapesp.

Abstracts – oral presentation

S158

OR. 04

Intestinal NA+/I- symporter (NIS) expression is regulated at post-transcriptional level by high concentrations of iodide

Nicola JP1, Susperreguy S1, Carrasco N2, Masini-Repiso AM1

1Centro de Investigaciones en Bioquímica Clínica e Inmunologia. CIBICI-CONICET. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba, Córdoba, Argentina; 2Department of Molecular Pharmacology. Albert Einstein College of Medicine, New York, USA

Dietary iodide absorption in the gastrointestinal tract constitutes the first step in iodide metabolism. Since this halogen is an essential component of the thyroid hormone, its concentrating mechanism is of considerable physiological importance. We have recently described NIS expression on the apical surface of the intestinal epithelium, central component of the iodide absorption system. The down-regulation of NIS by high iodide concentrations in the thyroid is related to the escape from Wolff-Chaikoff effect. This study evaluated the effect of iodide excess on intestinal NIS expression and the mechanism involved using the small intestine cell line IEC-6. Cells treated with an excess of iodide reduced significantly the iodide uptake process which correlated in time with a diminution of NIS expression at the plasma membrane, however NIS reduction in the whole protein extract was delayed. NIS mRNA level was decreased by the treatment with high iodide doses. Surprisingly, no mo dulation on NIS promoter activity in transiently transfected IEC-6 cells was evidenced, suggesting a non transcriptional process. Evaluation of NIS protein and mRNA half-life showed that in the presence of iodide NIS protein half-life was slightly shortened whereas mRNA stability was strongly reduced. In conclusion, iodide excess down-regulates intestinal NIS function and expression as it was similarly observed in the thyroid. The effect of high iodide concentrations regulates NIS expression through a complex mechanism that involves regulation at different levels. Although premature, these results seem to indicate that a post-transcriptional regulation is exerted on NIS by high concentrations of its own substrate.

OR. 05

The role of ret genetic variants in hereditary medullary thyroid carcinoma

Siqueira DR, Rocha AP, Meotti C, Estivalet A, Puñales MK, Maia AL.Thyroid Section, Endocrine Divison, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Background: Medullary thyroid carcinoma (MTC), a malignant neoplasia of C-cells of the thyroid, may occur sporadically or as part of the inherited cancer syndrome of multiple endocrine neoplasia type 2 (MEN2). The RET proto-oncogene is the susceptibility gene for hereditary MTC. A possible role of neutral sequence variants of RET on modifying MEN 2 clinical course is still a matter of debate. Objective: We investigated whether the RET neutral variants G691S, L769L, S836S, and S904S influence the clinical presentation and outcome individuals with MEN 2A. Material and methods: Our sample comprised 100 patients with a diagnosis of MTC attending at our Institution, belonging to 17 independent families. Results: All but three MEN 2A kindred had a mutation at codon 634 in exon 11 (90% of cases). The frequencies of RET polymorphisms were as follows: 18.1% L769L, 7.9% S836S and 18.1% S904S/G691S. We didn’t observe any association between these polymorphisms and clinical presentation (age, gender, pheochromocytoma, hyperparathyroidism, presence of local or distant metastases). Patients with the S836S variant were younger at diagnosis, but the difference did not achieve significance (18.8 ± 11.5 vs. 26.6 ± 16.3, p = 0.06). As gene dysfunction is present since birth, we assumed that the individual age at diagnosis would indicate the period of exposure, and thus we performed analyses using the Kaplan-Meier (KM) model. Interestingly, KM estimates of metastatic disease rates yielded distinct curves for S836S heterozygotes (P = 0.0085). Conclusion: These data suggest that the RET variant S836S might be associated with increased risk for metastatic disease at younger age in individuals with MEN 2A.

OR. 06

NIS mRNA levels are lower in papillary thyroid carcinomas but do not correlate with NIS protein localization in the neoplastic follicular cells

Morari EC1, Marcello MA1, Cunha LL1, Guilhen ACT1, Vassallo J2, Soares FA3, Ward LS1

1Molecular Genetics of Cancer Laboratory, Faculty of Medical Sciences (FCM), State University of Campinas (Unicamp); 2Laboratory Investigative and Molecular Pathology, CIPED, Faculty of Medical Sciences (FCM), State University of Campinas (Unicamp), Campinas, Brazil; 3Department of Pathology, Hospital AC Camargo – Antonio Prudente Foundation, São Paulo, Brazil

NIS is an intrinsic plasma membrane protein that mediates the active transport of I- in the thyroid. A recent report associated a reduced NIS mRNA expression in 13 thyroid malignant nodules to strong intracellular protein staining and suggested that this fact could be related to the inability of the protein to migrate to the basolateral membrane. The authors hypothesized that intracellular accumulation of NIS would promote a negative feedback on NIS mRNA synthesis and deficient protein migration. We examined a tissue array of 60 papillary thyroid carcinomas (PTC) including 42 classic and 18 follicular variants. An immunostaining score was given according to the percentage of positive follicular cells: 0 (negative), 1 (10%). Only 30% (18/60) of the PTC were positive for NIS, including 18 cases staining just the basolateral membrane. All PTC had mRNA of NIS quantified using RT-PCR. We observed two clearly different clusters of expression values (expressed as ∆Ct), below and above 0.5. The expression mRNA level of NIS was lower in patients classified as stage III compared to stage I or II (p = 0.0056). However, there was no relationship between NIS protein and gene expression. Also, we found no relationship between protein or gene expression and any other patient (age at surgery, sex, tobacco use) or tumor related factor of risk (tumor size, histology, invasion, metastasis or outcome). Our data confirmed our previous report relating NIS mRNA level to PTC aggressiveness. However, we found no correlation between mRNA levels and protein localization in the malignant cells.


S159

OR. 07

Percutaneous ethanol injection treatment of cervical lymph node metastases of papillary thyroid cancer

Perez CLS1, Mesa Jr C1, Trippia M2, Carvalho GA1, Graf H1

1Endocrinology Unit (SEMPR), Hospital de Clínicas da Universidade Federal do Paraná; 2Radiology Unit, Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil

Background: Percutaneous ethanol injection (PEI) is a noninvasive treatment regimen that has been used to treat diverse human neoplasms. In patients with recurrent thyroid cancer, nonsurgical treatment modalities have been attempted, not only to minimize the mortality rate but also to avoid the possible morbidity caused by repeated surgery. objectives: To evaluate the efficacy and safety of PEI therapy in patients with papillary thyroid cancer (PTC) cervical lymph node metastases. Methods: We evaluated 4 PTC patients with limited lymph nodes metastases (one to five involved nodes), between November 2007 and August 2008. All patients were considered poor surgical candidates or refused surgery, and were unresponsive to 131I therapy. Each metastatic lymph node was treated with ultrasound-guided PEI, and patients were followed clinically and by ultrasound (US). Results: We performed PEI on 8 recurrent cervical lymph nodes of 4 PTC patients. Mean follow-up was 7.3 months (range, 4 to 13 months). The lymph node median volume was significantly reduced, from 649 mm3 (range, 60 – 2120 mm3) to 370 mm3 (range, 0 – 760 mm3), with a mean reduction of 43%. One recurrent lesion disappeared by US. One patient developed multiple metastatic lymph nodes which precluded re-treatment with PEI. All patients tolerated well the PEI, referring only local pain and one patient had transient hoarseness. conclusion: We conclude that PEI is an alterative treatment for patients with limited cervical metastases from PTC who are not candidates for further surgical or radioiodine therapy.

OR. 08

Nuclear chromatin texture transformation may be related to the expression of genes involved in tumor progression and help identify papillary thyroid carcinomas with aggressive behavior

Ferreira RC, Morari EC, Silva JR, Guilhen ACT, Adam RL, Leite NJ, Matos PS, Assumpção LM, Vassalo J, Soares F, Metze K, Ward LSFaculty of Medical Sciences, University of Campinas (Unicamp), Campinas, Brazil

Background: We and others have previously demonstrated that the analysis of nuclear chromatin texture permits the distinction between benign and malign lesions of the thyroid. Methods: We used computerized nuclear morphometry and clinical and pathological well recognized indicators of tumor aggressiveness to examine 103 papillary thyroid carcinomas (PTC) patients. Histological signs of aggressiveness including capsular, blood or lymphatic invasion were present in 56 cases. All patients were submitted to a similar management protocol and followed-up for 13 to 248 months (Mo = 84 months). A total of 100 nuclei randomly chosen, digitalized and segmented from each case were examined and analyzed using software for the acquisition of images. Protein expression of nuclear tumor suppressor genes p53 and ATM was demonstrated by immunohistochemistry. Results: We observed that lesions with aggressive features at histology had a lower expression of both ATM (p = 0.006) and p53 (p = 0.001). Aggressive tumors were larger (p < 0.0001), had increased entropy values (p = 0,049), markedly higher fractal values (p = 0,004) and poorer chromatin texture organization (p = 0.044). conclusion: In summary, tumors with aggressive features also present subtle changes of the chromatin structure of nuclei, which cannot be detected in routinely HE stained paraffin sections, but are clearly evidenced in morphometric analysis. These changes may be related to the nuclear expression of genes involved tumor progression.

OR. 09

Novel involvement of NFkB subunit P65 in the lipopolysaccharide-induced NA+/I- symporter gene expression

Nicola JP, Nazar M, Mascanfroni I, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología. CIBICI-CONICET. Departamento de Bioquímica Clínica. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba, Córdoba, Argentina

Bacterial lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, exerts a variety of biological responses. The Na + /I- symporter (NIS)-mediated iodide uptake is the main rate-limiting step in thyroid hormonogenesis. We have recently reported the ability of LPS to stimulate the TSH-induced NIS expression. The aim of this work was to analyze the molecular mechanism involved in the LPS-induced NIS expression in the thyroid cell line FRTL-5. LPS increased the TSH-induced NIS mRNA expression and the functional activity of the transfected rat NIS promoter. Testing internal deletions of the promoter, we could define the NIS upstream enhancer (NUE) as responsible for the LPS stimulatory effect. Site-directed mutagenesis showed a critical role of a Pax8 binding site (named C) in LPS action. Bioinformatics analysis over NUE region looking for conserved sites of LPS canonical effectors, showed a novel conserved site for the transcription factor NFkB (region kB). Functional blockage of NFkB signaling by pharmacological agents antagonized LPS effect. Site directed mutagenesis of the kB site abrogates LPS stimulation. Co-expression of Pax8 and the main NFkB-subunit effector p65, but not p50 synergistically activated NIS promoter transcription in Cos-7 cells. Silencing of endogenous p65 levels by siRNA confirmed its participation as effector of LPS action on NIS expression. Furthermore, ChIP experiments corroborated that NIS is a novel target gene for p65 transactivation in response to LPS. In conclusion, our results thus reveal a new mechanism involving p65 in the LPS-induced NIS regulation, denoting a novel transcription factor related to NIS expression.


S160

OR. 10

Evidência de ação não genômica do hormônio tireoidiano (HT) no controle da expressão gênica e proteica do trans-portador de glicose glut4 em células 3T3-L1 (adipócitos)

Teixeira SS, Serrano-Nascimento C, Poyares LL, Machado UF, Nunes MTDepartamento de Fisiologia e Biofísica, ICB, USP, Sao Paulo, Brazil

O hormônio tireoideano (HT) exerce efeitos biológicos por mecanismos genômicos e não genômicos. Um dos genes induzidos pelo HT é o que codifica o GLUT4, principal transportador de glicose do músculo esquelético, cardíaco e tecido adiposo (TA), que exerce papel crucial na manutenção da homeostase glicêmica. Algumas ações não genômicas do HT resultam em aumento da estabilidade de transcritos, o que provoca rápido aumento do seu conteúdo e taxa de tradução. Objetivo: Avaliar, em células adiposas 3T3-L1, o efeito da exposição aguda (30 min) ao T3 sobre o conteúdo do mRNA e da proteína GLUT4, na presença e ausência de bloqueio prévio da transcrição gênica. Material e métodos: Células 3T3-L1 foram tratadas em condições específicas até sua diferenciação em adipócitos. Parte delas foi mantida em meio desprovido de HT (TX) por 24 h, após o que foram tratadas com T3 (10-9 M) ou salina. Parte das células recebeu actinomicina D (2 µg/ml) 1 h antes da adição do T3. Seguiu-se a avaliação do conteúdo de mRNA e proteína GLUT4 por Real Time-PCR e Western blotting, respectivamente. Resultados: Observou-se redução do conteúdo do mRNA e da proteína GLUT4 no grupo TX vs. controle, e seu rápido aumento, após 30 minutos da administração de HT. Esse efeito persistiu mesmo quando as células foram previamente tratadas com o inibidor da transcrição gênica (actinomicina D). conclusão: O T3 aumenta a expressão do mRNA e da proteína GLUT4, por mecanismos não genômicos, ação ainda não descrita na literatura e de potencial interesse clínico. Fapesp (06/52830-3).

OR. 11

Diferenças tecido-específicas na regulação da expressão da glutationa S-transferase por hormônios tireoi deanos

Faustino LC, Pires RM, Lima AC, Carvalho TMOLaboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brasil

objetivos: A glutationa-S-transferase (GST), no fígado, é inibida por hormônios tireoideanos (HTs). Estudamos a expressão da GST e da desiodase tipo I (DI) em diferentes fases do desenvolvimento e no hipo- e hipertireoidismo em animais com mutação no TRbeta, que impede a ligação do T3. Métodos: Coletamos fígado e rins de animais com 9 dias e adultos (8 semanas) sem tratamento. Animais normais (wt) e homozigotos (ho), de 8 semanas, foram tornados hipotireoideos pelo tratamento com propiltiouracil por 5 semanas. No hipertireoidismo, após propiltiouracil, injetou-se T3 por 21 dias. Avaliamos a expressão da DI, como controle, e da GST, por RT-PCR em tempo real. Os resultados foram normalizados pelo RNAm 36b4. Resultados e conclusão: Encontramos diminuição da DI no fígado e rins de homozigotos com 9 dias e adultos confirmando resistência periférica aos HTs. O T3 estimulou a DI nos animais normais (13 vezes), mas não nos homozigotos. No fígado de adultos dos homozigotos, a expressão da GST aumentou (3,8 vezes, p < 0,05) em relação aos wt. Surpreendentemente, aos 9 dias, a GST nos homozigotos estava diminuída (-90%, p < 0.001). Nos rins, a GST estava 40% menor nos homozigotos (wt: 1 ± 0,4; ho: 0,6 ± 0,2), e após T3 houve estímulo de 3 vezes. Enquanto a regulação da DI foi igual nos fígado e rins, a GST se comportou de forma distinta nos tecidos estudados. Nossos resultados mostram, pela primeira vez, a regulação diferencial da GST em fígado e rins por HT, sugerindo papéis distintos do TRbeta1 e TRalfa1, na regulação desse gene.

OR. 12

Estrogen increases thyroid hydrogen peroxide generation by dual oxidase in female rats

Ferreira ACF, Pantaleão TU, Freitas ML, Ginabreda MGP, Cardoso LC, Costa VMC, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brasil

Background: Dual oxidase (DuOx) is the enzyme responsible for thyroid H2O2 generation, which is essential for thyroperoxidase-catalyzed hormone synthesis. Increased H2O2 generation has been implicated in higher thyroid spontaneous mutagenesis rate and thus tumorigenesis, however no data on the effect of estrogen on H2O2 generation by DuOx is available. objectives: The aim of this study was evaluate the effect of ovariectomy and estrogen treatment on thyroid H2O2 generation by DuOx. Methods: Wistar female rats were ovariectomized (OVX) or sham-operated (control) and daily treated with either 0.7 mg (OVX + 0.7) or 14 mg (OVX + 14) estradiol benzoate/100 g body weight, s.c. Intact female rats were treated with the highest dose of estradiol (C + 14). After 21 days, animals were sacrificed by decapitation; thyroids were removed and processed in order to measure the calcium dependent H2O2 generating activity. Results: Serum estradiol levels were increased in both OVX and intact rats treated with the highest dose of estradiol (control = 31.01 ± 10.63; OVX + 14 = 690.9 ± 109.3; C + 14 = 740.0 ± 112.0 pg/ml). DuOx activity was reduced in OVX rats, when compared to control (control = 216.3 ± 56.90; OVX = 83.15 ± 25.55 nmoles H2O2.h-1. mg-1 protein), while estradiol treatment of OVX rats normalized DuOx activity (OVX + 0.7 = 154.8 ± 58.34; OVX + 14 = 155.7 ± 67.38). Treatment of intact rats with a high estradiol dose slightly increased DuOx activity (C + 14 = 270.3 ± 76.12), although not significantly. conclusions: Our results show that estradiol might positively regulate DuOx H2O2 generating activity, which could contribute to the higher prevalence of thyroid nodules among women. Financial Support: CNPq, Pronex, Capes, Faperj.


S161

OR. 13

A novel syndrome related to selenoproteins deficiency

Azevedo MF1-3, Barra GB2, Castro LC1, Amato AA1-3, Velasco LFR2, Godoy P2, Naves LA3, Neves FAR1

1Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasília (UnB); 2Sabin Institute and Laboratory of Clinical Analysis; 3Department of Endocrinology, University of Brasília (UnB); Brasília, DF, Brazil

The generation of active thyroid hormone or its inactivation is mediated by deiodinases. The synthesis of these enzymes requires incorporation of the rare aminoacid selenocysteine, through recoding of the UGA stop codon, in a unique process that creates the class of selenoproteins. The recognition of UGA requires a selenocysteine insertion sequence (SECIS) element in the 3’ untranslated region, and is mediated by the SECIS binding protein (SBP2). We describe a 11-year-old girl who presented with thyroid hormone dysfunction associated with short stature, delayed bone age, defective auditory function, progressive peripheral myopathy characterized by hypotonia and weakness, and moderate scoliosis with lateral trunk deviation. Serum TSH was slightly increased, with elevated T4 and reverse T3, while T3 levels were low. Low doses of T3 supplementation, but not T4, suppressed TSH. These findings suggest an impairment of the conversion of T4 to T3. Further analysis showed that the patient’s serum levels of another selenoprotein, glutathione peroxidase (GPx), were significantly reduced (GPx 11 U/g Hb; Normal Range 27.5 – 73.5 U/g Hb). Moreover, serum selenium was undetectable (Normal Range 50 – 150 mg/L). Genetic investigation demonstrated two novel nonsense heterozygous mutations affecting the SBP2 gene that create a truncated protein (R120X/R770X). Family investigation showed that inheritance is recessive. Since SBP2 is epistatic to selenoproteins synthesis, these mutations produced a generalized defect on selenoproteins, with a phenotype that had not been previously described. The description of this novel syndrome comprises a new perspective on the comprehension of the physiological role of selenoproteins in humans.

OR. 14

Effects of pentoxifylline, nicotinamide/allopurinol and methylprednisolone in the proptosis and inflammatory markers in patients with Graves’ ophthalmopathy (GO)

Fernandes LPS1, Cruz JB1, Pivotto DR1, Jorge EN2, Padovani CR3, Nogueira CR1, Mazeto GMFS1

1Endocrinology Division Internal Medicine Departament; 2Ophthalmology Departament; 3Biostatistics Departament, Faculdade de Medicina de Botucatu (Unesp)

Background: Graves’ ophthalmopathy is a therapeutic challenge and treatment outcome is often not satisfactory. Methods of treatment include high-dose glucocorticoids, orbital radiotherapy and orbital decompression. Because cytokines play an important role in the pathogenesis of the disease, cytokine antagonists and antioxidants might constitute a valuable tool for the management of GO. Novel treatments under investigation include pentoxifylline, that inhibits glycosaminoglycan synthesis, reduces interleukins, TNF-α and IFN-α expression in orbital fibroblasts; nicotinamide/allopurinol, that blocks proliferation of orbital fibroblasts and inhibits cytokine-induced expression MHC II antigens and sICAM-I from the same cells. objectives: Evaluate the response to treatment with oral pentoxifylline and the nicotinamide/allopurinol association compared with the standard therapy with intravenous methylprednisolone and its effects on cytokine levels. Methods: Prospective study involving 16 patients, with moderate to moderately severe GO with Clinical Activity Score (CAS) ≥ 3 divided into 3 groups of treatment: GI- oral pentoxifylline; GII- nicotinamide/allopurinol; GIII- intravenous pulse of methylprednisolone. All of them had similar levels of TSH, FT4, TRAb and TPOAb. The 3 groups werecompared on proptosis by measurement on exophtalmomether, CAS and levels of IL-6 before, during andafter the treatments (basal time, 3, 6 and 12 months). Results: The improvement on proptosisand levels of IL-6 was similar in the 3 groups. CAS showed better improvement in GII (3, 50-1, 00) than the standard methylprednisolone therapy. conclusion: Drugs acting on the inflammatory cascade that occurs in the orbital tissues could be a promise in GO treatment.

OR. 15

CTLA-4 318 polimorphisms are a factor of risk for Graves’ ophthalmopathy in Brazilian patients

Bufalo NE1, Santos RB2, Leite JL1, Guilhem MS1, Silva ACN1, Romaldini JH2, Ward LS1

1Medical Clinical, Lab. Gemoca, Unicamp; 2Division of Endocrinology, PUC-Campinas; Campinas, Brazil

Graves’ disease (GD) affects the thyroid, eyes and skin. CTLA-4 is a general autoimmunity gene which encodes a negative regulator of the T-cell immune response. Since T cells infiltrating the retrobulbar tissues are likely to play a key role in Graves’ ophthalmopathy (GO) pathogenesis, CTLA-4 may be considered as a candidate gene for GO. In order to study the influence of CTLA-4-318 polymorphism in the risk of GD and GO we studied 193 GD patients (161 women and 32 men, 39.3 ± 10.7 years old) matched on the basis of gender, age, and ethnicity to 200 healthy individuals (153 women and 47 men, 40.4 ± 15 years old) previously genotyped for CYP1A1 m1 and GSTP1 genes using PCR-RFLP. GO was present in 95 patients. GSTP1 variants were more frequent in GD patients (49.8%) than in controls (42%-p = 0.0002) as well as CYP1A1 variants (47.1% versus 28.2%-p < 0.0001). CTLA-4-318 had a similar distribution in GD and controls, however the polymorphisms were more frequent among patients with GO (16%) than in patients with no ophthalmopathy (8%-p = 0.0115). Indeed, the inheritance of a CTLA-4-318 variant increased the susceptibility to GO more than 2 times (OR = 2.482; 95%CI = 1.250-4.931). On the contrary, wild-type GSTP1 was more frequent among GO patients (44%) and acted as a protector factor (OR = 0.390; 95%CI = 1.410-5.13). We conclude that GSTP1 and other genes involved in xenobiotics detoxification, other than CYP1A1, may also be involved in GO risk. Although not important in the profile of risk for GD, the inheritance of CTLA-4-318 polymorphisms is an important determinant to the susceptibility for eye disease.


S162

OR. 16

Herpesvirus type 7 infection is a factor of risk for Graves’ disease in Brazilian but not in dutch patients

Leite JL1, Bufalo NE1, Santos RB2, Vos XG3, Romaldini JH2, Wiersinga WM3, Ward LS1

1Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences School, State University of Campinas (Unicamp); 2Division of Endocrinology, Department of Medicine, Catholic University of Campinas; Campinas, Brazil; 3Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

An inherited profile of genes related to the response to environmental aggressive factors such as viruses might be related to Graves’ Disease (GD) susceptibility and outcome. Human Herpesviruses (HHV) are ubiquitous, tissue tropism widespread, and have been found in the thyroid that can be a reservoir of latent HHV. In order to evaluate the relationship between HHV7 infection and TP53 apoptotic ability represented by 72p53 polymorphisms, we examined 318 Brazilian and 250 GD patients from the Netherlands paired with 399 Brazilian and 143 Dutch healthy individuals. All 886 patients and 483 controls were genotyped for HHV7 and TP53 codon 72 using Nested-PCR and PCR-RFLP. Patients were treated according to a same protocol, followed-up for Mo = 36 months and considered cured when they did not need antithyroid drugs to maintain euthyroidism one year after radioiodine therapy. The rate of HHV7 infection was similar in the control groups of the two countries (43.6% versus 42%; p = 0.768) but HHV7 was much more frequent among Brazilian (61%) than among the Dutch (32%) patients (p < 0.0001). HHV7 infection increased the risk for GD in the Brazilian population more than 3 times (OR = 3.133; 95% CI = 1.959-5.011; p < 0.0001), but did not affect Dutch population. The inheritance of less efficient Pro/Pro TP53 gene variants increased significantly the risk of GD development (OR = 5.196; 95%CI = 2.112-12.783; p < 0.0001) and also favored HHV7 infection (OR = 2.835; 95%CI = 1.100-7.310; p = 0.0275). Also, 72p53 variants augmented the risk for non-cure in the Brazilian patients (OR = 1.860; 95%CI = 1.015-3.410; p = 0.0446) suggesting that an inherited genetic profile may favor HHV infection and maintenance which, in turn, may initiate and perpetuate autoimmunity.

OR. 17

Effects of proinflammatory cytokines on type 2 deiodinase in nonthyroid illness syndrome

Wajner SM, Goemann IM, Maia ALSetor de Tireoide, Serviço de Endocrinologia do Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

Background: Nonthyroid illness syndrome (NTIS) refers to changes in thyroid hormone levels during critical illness. It has been speculated that cytokines may directly interfere with the deiodination of T4-to-T3. In humans, nearly all circulating T3 is originated from peripheral deiodination of T4 by type 2 deiodinase (D2). Conversely, data on D2 activity in NTIS is still controversial. objectives: To evaluate the effects of cytokines on D2 activity using a model that mimetizes the changes in interleukin-6 (IL6) and Tumoral Necrosis Factor (TNF) levels observed in critically ill patients, at physiological concentrations of cofactor and FT4 concentrations (20 pM). Methods: HEK-293 cells cultured in 6-well plates where transfected with 100 ng hD2 plasmid and incubated at different concentrations of IL6 (5, 25, 500 ng/L), TNF (1, 10 ng/L), or rT3 (0.3 or 1.18nmol/L). After 24hs incubation, culture medium was collected, and D2 activity was determined by measuring T4-to-T3 conversion based on the rate of appearance of enzymatically generated 125I. Results: The rate of T4-to-T3 conversion at IL6 concentrations of 5 or 25 ng/L, as observed in healthy individuals, were similar to that of controls (54.62 ± 2.2vs52.5 ± 5.3. p > 0.05). However, a significant decrease in D2 activity has occurred at IL6 concentrations of 500 ng/L (54.62 ± 2.2 vs. 14.44 ± 5.12. p < 0,001). Similar results were obtained using lower medium FT4 concentrations (2pM). No changes on D2 activity were observed when cells were incubated with TNF or rT3. conclusions: In a model that mimics the NTIS, IL6 induces a significant decrease in D2 activity suggesting that changes on D2 deiodination might be implicated on NTIS pathogenesis.

OR. 18

Triiodothyronine stimulates dendritic cell function through a PI3K-independent AKT pathway crucial role of thyroid hormone receptor β1, a new NF-kB target gene

Mascanfroni I1, Montesinos MM1, Alamino VA1, Susperreguy S1, Nicola JP1, Masini-Repiso AM1, Rabinovich GA2, Pellizas CG1

1Centro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI, CONICET. Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina; 2Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, IBYME, CONICET y Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

We demonstrated that mice dendritic cells (DC), the main antigen presenting cells, express TRβ1 with a preferential cytoplasmic localization. Moreover, physiological levels of T3 stimulated DC maturation, strengthened their T cell allostimulatory capacity and directed a T1-type cytokine response, involving cytoplasmic-nuclear shuttling of NF-kB. In this study we aimed at disclosing the signaling pathway involved in T3 action on DC and the role of TRβ1 in these effects. In turn we evaluated T3 effect on TRβ1 expression in DC and tested TRβ1 gene as a putative target of NF-kB. Bone marrow derived DC were treated with T3 (5nM) for 5 min to 18 h. Western blot of Akt/pAkt with or without PI3K inhibitors, co-immunoprecipitation, immunofluorescence and confocal microscopies revealed for the first time the involvement of the Akt pathway independently of PI3K in the recorded T3-induced effects. In turn, experiments conducted with siRNA-TRβ-transfected DC (TRβ expression abolished) prevented T3-induced DC maturation and function as well as Akt activation and IkB degradation, demonstrating a crucial role of TRβ1 in T3 effects at DC level. In turn, T3 increased TRβ1 expression in DC by a mechanism suppressed by NF-kB inhibitors. Chromatin immunoprecipitation (ChIP) analysis revealed a new functional NF-kB consensus site in the promoter region of TRβ1 gene. Our findings disclosed the molecular pathway involved in T3 effects on DC, through a cytoplasmic signaling not previously described for T3 action and dependent on TRβ1; described TRβ1 as a NF-kB target gene and also provided tools to manipulate the immunogenic potential of DC.


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OR. 19

Regulation of the thyroid dual oxidase activity by thyrotropin and iodine

Ferreira ACF, Freitas ML, Ginabreda MGP, Cardoso LC, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brazil

Background: Thyroperoxidase and NIS expression are tightly regulated by TSH, but DuOx seems not to be so dependent on the TSH pathway. DuOx is irreversibly inhibited in vivo by iodide. So it is important to better understand the regulation of DuOx by TSH and the role of DuOx in the escape from the Wolff-Chaikoff effect. We aimed to evaluate the effect of TSH and iodine on thyroid dual oxidase activity. Methods: Wistar rats were divided into the control (water ad libitum), MMI (0.03% methimazole in the drinking water, 10 days), and T4 (10 mg/100 g body weight, subcutaneously, 10 days). In order to evaluate the effects of iodide overload, rats were divided in control group (water ad libitum) and NaI (0.05% NaI in the drinking water for 1, 4 and 6 days). Results: DuOx activity was reduced in the thyroid of rats treated with MMI and increased when treated with T4. Treatment with NaI reduced DuOx activity, which was significant after 4 days of treatment. Discussion: In the present study, we have shown that the regulation of Duox by TSH seems to be different from other proteins involved in thyroid hormone biosynthesis, such as TPO and NIS. On the other hand, iodine overload reduced DuOx activity, similarly to other differentiation markers of the thyroid. Moreover, our data suggest a possible role of Duox in the escape of autoregulation, since the decrease in Duox activity by iodine treatment seems to be transient. Financial support: Pronex, CNPq, Faperj, Capes.

OR. 20

Triiodothyronine (T3) promotes the development of an antigen-specific cytotoxic response through modulation of dendritic cell (DC) function

Alamino VA, Mascanfroni ID, Montesinos MM, Susperreguy S, Masini-Repiso AM, Rabinovich GA, Pellizas CGCIBICI-CONICET, Depto. Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina

Mice DC, the main antigen presenting cells, express thyroid hormone receptor beta 1 (TRβ1) and physiological levels of triiodothyronine (T3) stimulates DC maturation and strengthens their T cell allostimulatory capacity directing a T1-type cytokine response (Mascanfroni et al. 22:1032,2008). In this study we investigated the ability of T3-stimulated DC to modulate 1) antigen-specific cytotoxicity in vivo and 2) antigen cross-presentation in vitro. For 1) and according to Calvo et al (J Immunol 181: 408,2008), DC were pulsed with OVA + T3 (5nM) for 30 min and i.v. injected to C57BL/6 mice. After 7 days mice were i.v. injected with a splenocyte mix (1:1; control:OVA257-264) stained with CFSE in two concentrations (0.5µM control:3µM OVA257-264). After 24 h, CFSE stained cell abundance from spleens was determined by flow cytometry. For 2) and in agreement to Fu et al (J Immunol Methods 335:90,2008) an overnight co-culture of DC pulsed with OVA + T3 and B3Z hybridoma cells (recognize OVA when presented via MHC I) was carried out. Levels of β-Gal (which expression is controlled by IL-2 promoter) were measured in supernatants. Our results indicated that 1) T3 significantly increased DC ability to stimulate a cytotoxic antigen-specific response, revealed by reduction of 3µM CFSE stained cells, 2) T3 significantly increased OVA cross-presentation evaluated through the increase of βGal expression. Our findings provide evidence for a critical role of T3 in the induction of a cytotoxic response that may have profound implications in immunotherapy including cancer, and broaden the knowledge of the interplay between immune and endocrine systems.

OR. 21

Eight new TPO mutations and high frequency of monoallelic mutations indicate genetic heterogeneity in patients with congenital hypothyroidism with total and/or partial iodide organification

Neves SC1, Dias V2, Viana M2, Chagas AJ2, Knobel M1, Medeiros-Neto G1, Rubio GS1

1Thyroid Unit (Lim25), University of Sao Paulo Medical School, Sao Paulo, Brazil; 2NUPAD, Medicine School of the University of Minas Gerais, Belo Horizonte, Brazil

introduction: Congenital Hypothyroidism (CH) affects 1/3000 newborns. Thyroid peroxidase (TPO) gene mutations are the most frequent genetic defects associated with monogenic disorders of the thyroid gland. objectives: To identify TPO gene mutations in patients with CH with total (DIIT) or partial (DIIP) iodide organification defects and to perform in silico analysis of the mutations. Patients and methods: We included thirty six patients, 15 with DIIT (iodide discharge > 51%) and 21 with DIIP (iodide discharge between 25-50%). Amplification and sequencing of the promoter and 17 exons of TPO gene were performed. Results: Eight new sequence alterations were identified: Leu68Ile, Gly319Glu, Ala426Gly, Arg584Gln, Val618Met, Pro883Leu, Ala909Thr, and A909fsX49 as well as four previously described mutations: 396fsX76, Gln660Gly, Arg665Trp, Cys838Ser were detected. Homozygous mutations were identified in two patients with DTII. Two patients (one with DTII and one with DPII) were carryied compound heterozygous mutations. TPO monoallelic mutations were identified in 60% of patients whom harbor TPO mutations (3 with DIIP and 3 with DIIT). TPO mutations were not found in 100 Brazilian normal controls. Sequence alignment studies and in silico structural analysis of the TPO protein suggested that the new mutations are bona fide mutations. conclusions: High frequency of TPO monoallelic mutations was detected in patients with DIIT and DIIP. In both groups of patients the mutations were located all throughout the gene, in the extracellular as well as in the intracellular domain. Only two mutations have been identified in more than one patient, indicating the genotypic heterogeneity in this group of newborns with CH.


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OR. 22

Correlação entre a dosagem de iodo em urina de 24 horas e amostra isolada nos pacientes submetidos a tratamento com iodo radioativo

Padovani RP1-2, Marone MS2, Vieira JGH1, Maciel RMB1, Biscolla RPM1

Disciplina de Endocrinologia, Universidade Federal de Sao Paulo1; Serviço de Medicina Nuclear da Santa Casa de Misericórdia de Sao Paulo2; Sao Paulo Brasil

introdução: O sucesso do uso do radioiodo (131I) no tratamento do paciente com carcinoma diferenciado de tiroide está relacionado a uma série de fatores que podem alterar a efetividade da dose, entre eles, a fração de radiação que é absorvida pelos restos tiroidianos e metástases. Estratégias para aumentar a captação do 131I incluem a elevação do TSH e a depleção do pool de iodo. A concentração de iodo na urina (iodúria) é, atualmente, o marcador bioquímico mais utilizado para a avaliação do pool de iodo plasmático antes do tratamento com 131I. objetivo: O objetivo deste trabalho foi comparar a dosagem da iodúria em amostras de urina isolada e de 24 horas. Métodos: Foram colhidas amostras de urina isolada e de 24 horas, antes e após dieta pobre em iodo, de 295 pacientes com diagnóstico de carcinoma diferenciado de tiroide tratada com tiroidectomia total e em preparo para o tratamento com 131I. A iodúria foi quantificada por método semi-automatizado. Resultados: As médias da iodúria de 24 horas e da amostra isolada foram 20,15 µg/dl e 23,05 µg/dl respectivamente e ambas apresentaram boa correlação (R = 0,52). conclusão: As iodúrias em amostra isolada e nas amostras de 24 horas apresentaram boa correlação, podendo a amostra isolada ser utilizada como marcador de preparo dos pacientes. A facilidade da coleta de amostras isoladas frente à coleta de 24 horas representa benefício na avaliação do pool de iodo do paciente submetido ao tratamento com 131I.

OR. 23

Determinación de atpasas como opción para diagnostico de malignidad en nódulo tiroideo

Hurtado-Lopez LM1, Dominguez Fonseca CB1, Velazquez-Fernandez D2

1Clínica de tiroides Hospital General de México; 2Instituto Nacional de Medicina Genomica; México

antecedentes: Aun existen biopsias por aspiración no diagnosticas, la utilización de la fosforilación oxidativa es diferente en las células cancerosas con respecto a las benignas, esto podría ser un marcador diagnostico de cáncer. objetivo: Evaluar, en estudio piloto, si existe diferencia en la expresión molecular de ATPasas relacionadas a la fosforilación oxidativa entre tejido con cáncer tiroideo y sin cáncer tiroideo. Material y Método: Estudio experimental. En tejido de 24 nódulos tiroideos consecutivos. Variable a evaluar, expresión molecular por rtPCR de ABCC3, ATP10A y ATP13A4 y ATP6V0E2. Resultados: Los diagnósticos finales en esta muestra fueron: 7 casos de bocio, 14 con cáncer papilar de tiroides (CPT), 1 con cáncer folicular y 2 casos con tiroiditis de Hashimoto En relación a la expresión de ATPasas evaluadas, se observó que existe una mayor expresión de ABCC3, ATP10A y ATP13A4 en los casos de CPT que en los BMN, mientras que la ATP6V0E2 se encuentra con menor expresión en los casos de CPT que en el BMN. La media de sobreexpresión de los casos analizados para ABCC3 fue de 8.31 en cáncer y 6.33 en bocio (p = 0.026), para ATP10A fue de 6.56 en cáncer y 5.42 en bocio (p = 0.00), para ATP13A4 fue de 8.99 en cáncer y 7.08 en bocio (p = 0.003), de ATP6V0E2 fue de 9.08 en BMN y 7.17 en CPT (p = 0.020). conclusión: La determinación de ATPasas puede ser un método de evaluación para determinar la presencia de malignidad.

OR. 24

Lack of association between subclinical hypothyroidism and emerging cardiovascular risk factors in a population-based study the Japanese-Brazilian Thyroid Study

Sgarbi JA1-2, Matsumura L1, Kasamatsu T1, Maciel RMB1

1Laboratory of Molecular Endocrinology, Division of Endocrinology, Federal University of Sao Paulo; Sao Paulo, Brazil; 2Division of Endocrinology, Department of Medicine, Faculdade de Medicina de Marília; Marília, Brazil

Background: Whether subclinical hypothyroidism (SCH) is associated to an increased risk of coronary heart disease, the causes may be not explained by an excess of traditional cardiovascular risk factors. However, there are few and inconsistent data concerning the role of the emerging blood markers. objective: To investigate whether SCH is associated to increased blood levels of nontraditional biomarkers for atherosclerosis risk. Methods: A cross-sectional study in an entire population (n = 1330) of Japanese-Brazilians. We compared the mean values and frequencies of elevated blood biomarkers of pro-inflammatory state and atherosclerosis, such as C-reactive protein (CRP), interleukin-6 (IL-6), apolipoprotein B, homocysteine, urinary albumin excretion and HOMA-IR in SCH individuals with those in euthyroidism. Results: Euthyroidism was found in 82.3% and SCH in 6.2% of the participants. After adjusting for age, gender, presence of other cardiovascular risk factors and by the use of statin, there was no statistical difference in the serum means or in the percentages of elevated CRP, IL-6, apoliprotein B or homocysteine in SCH individualscompared to euthyroid controls. Similarly, HOMA-IR and urinary albumin excretion showed no difference between the groups. In a subgroup analysis for individuals with clearly high serum TSH levels ( > 10 -19.9 mU/L), we again found no difference in the studied variables compared to the euthyroid group. conclusions: In this large population-based study, we found no relationship between SCH and the emerging cardiovascular risk factors. These findings argue against that low-grade chronic inflammation could be responsible for the increased cardiovascular risk in individuals with SCH.


abstracts – Poster Presentation

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CliniCal Thyroidology

Po. 001 Função tireoidiana em crianças e adolescentes com síndrome de Down .............................................................S172 Monteiro SHV, Barros CJV, Imbroise R, Ribeiro MG, Beserra ICR, Guimarães MM

Po. 002 Absence of PAX-8 and TSH receptor genes mutations in patients with thyroid dysgenesis ......................................S172 Brust ES, Beltrao CB, Chammas MC, Juliano AG, Watanabe T, Sapienza MT, Marui S

Po. 003 Densidad mineral osea y anticuerpos al receptor de TSH en enfermedad de Graves postratamiento: premenopausia versus posmenopausia ........................................................................................................................S172

Ercolano M, Drnovsek M, Silva Croome MC, Moss M, Fuentes A, Viale F, Gauna A, Laguna J, Antonovic G

Po. 004 Long term follow up of congenital hypothyroid patient due to IVS30 + 1G > T mutation which promote endoplasmic reticulum enlargement and altered expression of specific thyroid genes........................................S173

Galrão AL, Rubio IGS, Pardo V, Knobel M, Possato RF, Camargo RRY, Ferreira MA, Kanamura CT, Gomes AS, Medeiros-Neto G

Po. 005 Manifestações raras em doença de Graves: relato de caso .....................................................................................S173 Sacramento Monte RS, Guedes DSN, Perez A, da Cunha AMF, Soares DV

Po. 006 In vivo efects of triiodothyronine (T3) on mouse B lymphocytes .................................................................................S173 Bloise FF, Cordeiro A, Mello-Coelho V, Rumjanek V, Pazos-Moura C

Po. 007 Avaliação ultrassonográfica da tireoide, determinação da iodúria e concentração de iodo em sal de cozinha utilizado por escolares de Ribeirão Preto, São Paulo, Brasil ....................................................................S174

Alves MLD, Duarte GC, Navarro AM, Tomimori EK

Po. 008 Hypothyroidism presented as slipped upper epiphysis, hydrocele, short stature and hypogonadism ................S174 Lauand TCG, Santana CM, de Sousa PB, Marques ELV, Pedrosa HC

Po. 009 Treatment of Graves’ ophthalmopathy with an antagonist of PPAR-gamma: preliminary results...........................S174 Bloise W, Mimura LY, Moura J, Nicolau W

Po. 010 Exoftalmometria y apertura palpebral en adultos mexicanos...................................................................................S175 Flores-Rebollar A, Navarro-Lara A, Moreno-Castañeda L, López-Carrasco G, Montaño-Lechuga MC, Ruiz-Juvera A,

Sepúlveda-Méndez J, Natera-Cruz E, González-Treviño O

Po. 011 Avaliação da função muscular, tolerância ao exercício, capacidade funcional e aspectos clínicos no hipertireoidismo subclínico ..............................................................................................................................................S175

Chachamovitz DSO, Jerusalmi ALC, Vigário PS, Cordeiro MFN, Castro CLN, Vaisman M, Teixeira PFS

Po. 012 Madre hipoparatiroidea e hipotiroidea y recien nacido ............................................................................................S175 Falcón-de-Legal E, Menoni-de-Lezcano M

Po. 013 Evaluation of quality of life in patients with Graves disease treated with methimazole and radioiodine – preliminary results in a small population ........................................................................................................................S176

Corralo GCMB, Villagelin D, Santos RB, Cunha M, Malouf EZ, Romaldini JH

Po. 014 Audiologic evaluation in patients with acquired hypothyroidism ..............................................................................S176 Santos KTP, Martins RHG, Dias NH, Lapate RL, Carvalho LR, Mazeto GMFS

Po. 015 Comparison of different doses of radioiodine in severe Graves hyperthyroidism: a clinical trial with historical control ................................................................................................................................S176

Dora JM, Machado WE, Andrade VA, Maia AL

Po. 016 Etiologias do hipotireoidismo congênito na região de Ribeirão Preto – São Paulo – Brasil em crianças nascidas entre 1994 e 2005 .......................................................................................................................S177

Magalhães PKR, Maciel LMZ

Po. 017 Avaliação da função e da auto-imunidade tireoidianas em mulheres acima de 35 anos, infectadas pelo HIV ...............................................................................................................................................................................S177

Carvalho LG, Vaisman M, Barroso PF, Panico ALBG, Teixeira PFS

Po. 018 TSHoma: desafio diagnóstico – relato de caso .............................................................................................................S177 Muniz TZ, Ourdakian MK, Fernandes LPS

Po. 019 Pseudotumor inflamatório de órbita: um diagnóstico diferencial de oftalmopatia de Graves ............................S178 Caminha LSC, Rebelo E, Sousa PAM, Oliveira RA, Buesco A,Vaisman M

Po. 020 Human DuOx 2 promoter activity regulation by hormones and transcripition factors ............................................S178 Cardoso LC, Querino AL, Costa MEWF, Carvalho DP, Santisteban P

Po. 021 Influência da pluviometria e sazonalidade nos níveis de TSH na triagem neonatal de estado da região amazônica – Brasil ..........................................................................................................................................S178

Fernandes-Caldato MC, El Husny AS, Correa ARR, Ferreira AO, Silveira EC.

Po. 022 A case of congenital hipothyroidism with total iodine organification associated to monoallelic mutations ......S179 Mezalira PR, Neves SC, Dias V, Viana M, Chagas AJ, Knobel M, Medeiros-Neto G, Rubio IGS

Po. 023 Resposta cardiopulmonar de pico e pós-esforço submáximo de pacientes com hipertireoidismo subclínico exógeno .............................................................................................................................S179

Vigário PS, Mendes ALM, Chachamovitz DSO, Teixeira PFS, Oliveira FP, Vaisman M

Abstracts – poster presentation – index

S167

Po. 024 Hypothyroidism causes width’s reduction in testicular germinative epithelium .......................................................S179 Romano RM, Salgado RM, Nunes MT

Po. 025 Hipertiroidismo y embarazo: crisis tirotóxica materna e hipotiroidismo congenito central con hipertiroidismo neonatal transitorio ........................................................................................................................S180

Gutierrez S, Calabrese MC, Abalovich M, Alcaraz G, Otero J, Stivel M

Thyroid auToimmune diseases & geneTiCs

Po. 026 A meta-analysis of patients with chronic hepatitis C virus treated with interferon-alpha to determine the risk of induced thyroid autoimmunity ....................................................................................................S180

Andrade LJO, Bittencourt AV, Atta AM, Parana R

Po. 027 Thyroiditis in patients with hepatitis C infection treated with interferon alpha – revisional study ............................S180 Andrade LJO, Bittencourt,AV, França LS, Atta AM, Parana R

Po. 028 Tireoidite autoimune crônica em lactente com síndrome de Down .........................................................................S181 Dias EO, Martin RM, Miranda D, Tomimori EK, Knobel M, Camargo RA

Po. 029 Prevalence of thyroid auto-immunity in patients with prolactinoma ..........................................................................S181 Saldanha F, Violante AHD, Freitas MMW, Loureiro C, Ballarini M, Lamounier Filho A, Naliato ER, Vaisman M

Po. 030 Avaliação da presença de anticorpos antitireoperoxidase e disfunção tireoidiana na síndrome de Down .....S181 Barros CJV, Monteiro SHV, Imbroise R, Ribeiro MG, Beserra ICR, Guimarães MM

Po. 031 Interaction of type 2 iodothyronine deiodinase THR92ALA and peroxissome proliferactor-activated receptor gama-2 Pro12Ala polymorphisms in the modulation of insulin resistance ................................................S182

Estivalet AAF, Leiria LB, Canani LH, Maia AL, Crispim D

Po. 032 Is there a different risk profile for Graves’ disease in children and adults? .................................................................S182 Cury AN, Bufalo NE, Longui CA, Scalissi NM, Monte O, Ward LS

Po. 033 Autoimunidade tireoidiana e abortamento espontâneo ............................................................................................S182 da Cunha AB, Meira DM, de Brito KRS, Thomaz LPM, da Cruz RP

Po. 034 Síndrome de anticuerpos antifosfolipido, enfermedad de Graves Basedow y carcinoma papilar de tiroides ..S183 Falcon-de-Legal E, Almiron R, Bogado L

Po. 035 Evaluation of thyroid patients infected by hepatitis C virus: correlation with polymorphisms of CTLA-4 gene .....S183 Lima EU, Barros RK, Knobel M, Mendes-Correa MC, Zambrini H, Marui S

Po. 036 Maior chance de angioedema em pacientes com urticária crônica idiopática e doenças da tireoide..........S183 Missaka RFBG, Penatti HC, Silvares MRC, Nogueira CR, Mazeto GMFS

Po. 037 Role of parity and estrogens in the risk of autoimmune thyroid disease in a population-based study of Japanese-Brazilians .......................................................................................................................................................S184

Sgarbi JA, Matsumura L, Kasamatsu T, Maciel RMB

Po. 038 Thyroid cells up-regulate toll-like receptor 4 expression and pro-inflammatory mediators in response to LPS stimulation: new players in the innate immune response? ...............................................................................S184

Nicola JP, Gatti G, Maccioni M, Masini-Repiso AM

Po. 039 A novel mutation in selenocystein binding protein type 2 gene is associated with abnormal thyroid hormone metabolism: case report .................................................................................................................................S184

Leiria LB, Meyer ELS, Dora JM, Maia AL

Po. 040 Selenio y autoinmunidad tiroidea ...................................................................................................................................S185 Calabrese MC, Abalovich M, Gutierrez S, Elias N

Po. 041 Mixedema pretibial grave ................................................................................................................................................S185 Munizaga F, Hidalgo C, Munizaga

Po. 042 Detecção da resistência ao hormônio tireoidiano pela triagem neonatal .............................................................S185 Magalhães PKR, Maciel LMZ

Thyroid hormone aCTion & meTabolism

Po. 043 Efeito do treinamento físico de natação sobre o ganho de massa corporal e função tireoidea de ratas ovariecto mizadas ..............................................................................................................................................................S186

Ignacio DL, Fortunato RS, Frankenfeld TGP, Carvalho DP

Po. 044 Iodotironinas desiodases são reguladas pela administração crônica de 3,5-diiodotironina ...............................S186 Padrón AS, Pantaleão TU, Andrade BM, Araújo RL, Carvalho DP

Po. 045 Efeito da restrição alimentar e da administração de triiodotironina (T3) sobre a morfometria cardíaca em ratos obesos ...............................................................................................................................................S186

Marino J, Luvizotto RAM, Nascimento AF, De Sibio MT, Almeida NCP, Olimpio RMC, Nogueira CR


S168

Po. 046 Bone and mineral metabolism in resistance to thyroid hormone ..............................................................................S187 Dare GLR, Magalhães PKR, de Castro M, Maciel LMZ

Po. 047 Thyroid hormone transport in erythrocytes from patients with hyperthyroidism and hypothyroidism ...................S187 Oliveira AS, Azevedo MF, Neves FAR, Simeoni LA

Po. 048 Genomic and non-genomic intracellular pathways involved in thyroid hormona mediated T lymphoma cell proliferation .................................................................................................................................................................S187

Barreiro Arcos ML, Farías RN, Klecha AJ, Sterle HA, Genaro AM, Cremaschi GA

Po. 049 Efeito da administração de triiodotironina (T3) sobre o dano de DNA em animais com obesidade induzida por dieta ..........................................................................................................S188

Sibio MT, Luvizotto RAM, Olimpio RMC, Marino J, Oliveira Jr SA, Oliveira LRC, Calvi SA, Favero DM, Nogueira CR

Po. 050 A case study of the thyroid hormone receptor alpha homodimer interface ............................................................S188 Ribeiro ICJ, De Farias RF, Bampa G, Neves FAR, Polikarpov I, Togashi M

Po. 051 Glucocorticoids prevent thyroid hormone action at the level of the initiation of the immune response. Role of dexamethasone on triiodothyronine (T3) effects on mice dendritic cell characteristics ...........................S188

Montesinos MM, Mascanfroni ID, Alamino VA, Susperreguy S, Masini-Repiso AM, Rabinovich GA, Pellizas CG

Po. 052 Acute T3 administration reduces polyadenylation of βTSH mRNA of hypothyroid rats: a non genomic action of thyroid hormone ...................................................................................................................S189

Souza PB, Bruneto EL, Nunes MT

Po. 053 Efeito do hormônio tireoideano sobre o conteúdo e translocação do transportador de glicose GLUT4 no tecido adiposo: possível ação não-genômica do hormônio ..............................................................................S189

Croffi RV, Teixeira SS, Machado UF, Nunes MT

Po. 054 Low triiodothyronine (T3) plasma levels in congestive heart failure (CHF) are associated with other neurohormonal and inflammatory prognostic markers of the disease ..........................................................S189

Brenta G, Thierer J, Vainstein N, Acosta A, Boero L, Sutton M, Brites F

Po. 055 TSH increases nitric oxide synthase III expression through a PKA-dependent AKT activation ..................................S190 Fozzatti L, Nicola JP, Nazar M, Velez ML, Lucero AM, Pellizas CG, Masini-Repiso AM

Po. 056 Síndrome eutiroideo enfermo en diabetes tipo 2 .........................................................................................................S190 Juarez XE, Diaz SA

Po. 057 Iodine excess increases seleproteins expression in rat thyroid ....................................................................................S190 Fuziwara CS, Raimundo SG, Leoni SG, da Silva MJ, Ricarte-Filho JC, Kimura ET

Po. 058 Detecção de fitoquímicos capazes de promover o aumento da captação tireoidea de iodeto in vitro e in vivo .................................................................................................................................................S191

Santos MCS, Gonçalves CFL, Souza ECL, Braga WMO, Ginabreda MGP, Ferreira ACF, Carvalho DP

Po. 059 Substitution of serine for proline in the active center of type 2 iodothyronine deiodinase substantially alters its in vitro biochemical properties but not its function in vitro ............................................................................S191

Goemann IM, Harney JW, Maia AL, Larsen PR

Po. 060 O iodo altera a expressão do mRNA de pendrina: estudo in vitro e in vivo .............................................................S191 Calil-Silveira J, Serrano-Nascimento C, Nunes MT

Po. 061 A novel role of the NFKb transcription factor in the TSH-regulated thyroid gene expression ...................................S192 Nicola JP, Nazar M, Mascanfroni ID, Pellizas CG, Masini-Repiso AM

Po. 062 Efeito da ovariectomia e do tratamento com 17β-estradiol sobre a função tireoidea e a ativação da via Ras-pERK em tireoides murinas ...........................................................................................................S192

Pantaleão TU, Mendonça KT, Mousovich Neto F, Rosenthal D, Corrêa da Costa VM

Po. 064 Eliminacion de la deficiencia de yodo en Paraguay y riesgo de exceso de yodo ................................................S192 Ovelar EC, Redondo J, Zarza Z, González N, Jara J, Pretell EA

Po. 063 Sustained elimination of iodine deficiency in Peru for about 15 years ......................................................................S193 Pretell EA, Higa AM

Thyroid nodules & CanCer

Po. 065 Patients with familial papillary thyroid cancer have a similar outcome than those with sporadic tumors ...........S193 Pitoia F, Cross G, Salvai ME, Nuñez S, Haseitel M, Abelleira E, Niepomniszcze H

Po. 066 Patients with insulin resistance have less aggressive papillary thyroid cancers .......................................................S193 Rezzónico JN, Rezzónico M, Pusiol E, Pitoia F, Niepomniszcze H

Po. 067 Caracteristicas del bocio nodular benigno en pacientes evaluados en consultorios privados de la ciudad de Buenos Aires ..........................................................................................................................S194

Antunez PB, Licht SD


S169

Po. 068 Alta incidência de alterações morfológicas tireoidianas em acromegálicos ........................................................S194 Assupção CB, Carvalho GM, Fernandes-Caldato MC, Oliveira RG

Po. 069 Radioiodine treatment of childhood differentiated thyroid cancer (DTC) did not increase the risk of a second pri-mary malignancy or of delayed puberty but resulted in azospermia in one patient .............................................S194

Sztal-Mazer S, Cardoso-Demartini A, Nesi S, Mesa Jr C, Lacerda L, Graf H

Po. 070 Expression of vascular endothelial growth factor-A (VEGF-A) and its receptor (VEGFR-2) in medullary thyroid carcinoma ......................................................................................................................................S195

Capp C, Siqueira D, Wajner SM, Meurer L, Assis Brasil B, Maia AL

Po. 071 Metástase óssea como apresentação inicial do carcinoma diferenciado da tireoide ........................................S195 Balarini LD, Blummenberg S, Cremasco T, Dias EO, Freitas LV, Mendes T, Kaskus LE, Renaux L, Santos JG, Silva GB, Santos JB,

Sasson P

Po. 072 Cáncer de tiroides detectado en el embarazo ............................................................................................................S195 Cabezón CA, Carrizo C

Po. 073 Microcarcinoma papilífero em hipertireoidismo ..........................................................................................................S196 Blumemberg S, Renaux L, Sasson P, Mansur V, Kaskus L, Góis C, Frota D, Jesus R, Panernari T

Po. 074 A obesidade dobra o risco de desenvolvimento de câncer diferenciado da tiroide nas mulheres ...................S196 Castaldi SA, Marcello MA, Cunha LL, Assumpção LVM, Ward LS

Po. 075 A presença de linfócitos infiltrantes está associada com características de agressividade tumoral, com o prognóstico e com a expressão de genes supressores tumorais nos carcinomas papilíferos da tiroide ........S196

Cunha LL, Morari EC, Guilhen ACT, Bufalo NE, Vassallo J, Soares FA, Ward LS

Po. 076 Anticuerpos a tiroglobulina: utilidad en seguimiento de carcinoma diferenciado de tiroides ............................S197 Gauna A, Silva Croome M, Viale Fanny, Guillén C

Po. 077 Prospective evaluation of percutaneous ethanol injections in benign thyroid nodules ..........................................S197 Perez CLS, Bizeli R, Graf H, Carvalho GA

Po. 078 Impact of retinoic acid on advanced thyroid carcinoma – 4 years of follow-up .....................................................S197 Coelho SM, Vaisman F, Buescu A, Corbo R, Carvalho DP, Vaisman M

Po. 079 Elevacion endogena de TSH como adyuvante al radioyodo en el tratamiento del bocio multinodular ............S198 Flores-Rebollar A, Moreno-Castañeda L, Ruiz-Juvera A, López-Carrasco G, Sepúlveda-Méndez J, González-Treviño O

Po. 080 Escrutinio ultrasonografico tiroideo en una poblacion adulta en México ...............................................................S198 Flores-Rebollar A, Navarro-Lara A, Moreno-Castañeda L, López-Carrasco G, Ruiz-Juvera A, Sepúlveda-Méndez J, Gómez V,

Valles V, González-Treviño O

Po. 081 Presunción de la incidencia de cáncer de tiroides en capital federal y el gran Buenos Aires (período 2003-2007) (thyroid cáncer incidence in Buenos Aires) ...............................................................................S198

Faure E, Soutelo MJ, Faraj G, Juvenal G, Lutfi RJ

Po. 082 Iodothyronine deiodinase type 3 expression in thyroid neoplasias ...........................................................................S199 Zennig N, Wajner SM, Maia AL

Po. 083 Efecto de TGF-β1, TGF-β2 y TGF-β3 en células de cáncer folicular de tiroides humanas: rol del estrés oxidativo .S199 Oglio R, Thomasz L, Juvenal GJ, Pisarev MA

Po. 084 Tiroglobulina en nódulos tiroideos benignos: presencia de efecto hook .................................................................S199 Viale F, Dios A, Lowenstein A, Glikman P, Reyes A

Po. 085 Insular thyroid carcinoma, a very aggressive – thyroid tumor .....................................................................................S200 Miasaki FY, Mesa Jr C, Carvalho GA, Ludwig VB, Graf H

Po. 086 Influencia del tamaño nodular en el resultado de la punción con aguja fina (PAF) en nódulos tiroideos menores de 5 cm ...............................................................................................................................................S200

Díaz R, Wohllk N

Po. 087 Puncion biopsia aspirativa con aguja fina (PBAF) en lesiones extratiroideas localizadas en cuello ...................S200 Lowenstein A, Santoro S, Genoni V, Olstein G, Laudi R, Reyes A

Po. 088 Papillary carcinoma in a thyroglossal duct cyst ...........................................................................................................S201 Perez CLS, Ramos HE, Pedruzzi PAG, Mesa Jr C, Graf H, Carvalho GA

Po. 089 Successful surgical resection of papillary thyroid cancer bone metastases preceded by arterial embolization .......................................................................................................................................................................S201

Perez CLS, Wesley SRAG, Bortoloni LGC, Moura M, Ludwig VB, Carvalho GA, Graf H

Po. 090 Renal cysts as cause of false-positive in post-ablative dose whole bone scan (WBS) with I131 for differentiated thyroid carcinoma treatment ...................................................................................................................S201

Santana CM, Souza PB, Lauand TGC, Santos AGA, Prado Jr LM, Pedrosa HC

Po. 091 Frecuencia del cancer de tiroides en patología quirúrgica tiroidea ........................................................................S202 Falcon-de-Legal E, Ramos M


S170

Po. 092 Carcinoma papilar de tiroides familiar – nuestra experiencia ...................................................................................S202 Faure E, Schwarsztein D, Novelli JL, Cale J, de Candia L, Juvenal G, Lutfi R

Po. 093 Marcación prequirúrgica con arpón metálico en metástasis cervicales de carcinoma papilar tiroideo ..........S202 Faure E, Lambertini R, Farías P, Figari M, Villar A, Simkin D

Po. 094 Análise da prevalência de carcinoma papilífero familiar de tireoide ......................................................................S203 Gomes EMS, Buescu A, Vaisman M

Po. 095 Anormalidades morfológicas da tireoide em familiares de primeiro grau de portadores de carcinoma papilífero de tireoide ....................................................................................................................................S203

Gomes EMS, Buescu A, Vaisman M

Po. 096 Avaliação da eficácia do tratamento com iodeto-131I em pacientes com carcinoma diferenciado de tireoide ...........................................................................................................................................................................S203

Martins Filho R, Matos PS, Lima MCL, Santos AO, Ramos CD, Ward L, Assumpção LVM, Etchebehere ECSC

Po. 097 Concomitância de carcinoma papilífero e linfoma MALT de tireoide ......................................................................S204 Melo GM, Sguillar DA, Baptistella LC, Souza RAS

Po. 098 Diagnóstico de câncer de tireoide: concordância entre punção aspirativa com agulha fina e exame anatomopatológico .........................................................................................................................................................S204

Kruschewsky LS, Azi NM, Lessa B, Tricolli R, Caracas N, Santos RRA

Po. 099 Thyroglobulin detection in fine- needle aspirates of cervical lymph nodes in non-thyroidectomized patients ...S204 Bergoglio L, Mahler G, Cuvertino E, Geres A, Romero N, Mereshian P, Iturbe B

Po. 100 Retrospective evaluation of pacients with a differentiated thyroid cancer (DTC) observed in the ambulatory of endocrinology service of Taguatinga regional hospital (HRT) .........................................................S205

Sousa PB, Santana CM, Pedrosa HC, Faria CP, Azevedo GFM, Lauand TGC

Po. 101 Differentiated thyroid carcinoma: alteration in size pattern along more than 30 years of follow-up ....................S205 Assumpção LVM, Denardi FC, Moura-Neto A, Melo TG

Po. 102 Evaluation of bone mineral density in patients with TSH suppressive therapy due to differentiated thyroid carcinoma .............................................................................................................................................................S205

Melo TG, Denardi FC, Moura-Neto A, Assumpção LVM

Po. 103 Carcinoma papilar de tiroides y enfermedad de Graves: presentacion de un caso ............................................S206 Juarez XE

Po. 104 Análisis con cinco escalas de estadificacion pronóstica de los pacientes con cancer diferenciado de tiroides del hospital de especialidades del Centro Medico “La Raza” .................................................................S206

Sosa CA, Mora HS, Alamilla LL, Velázquez CFJ, Galindo RME

Po. 105 Cáncer diferenciado de tiroides (CDT): eficiencia de las distintas metodologías diagnosticas en adenopatias cervicales sospechosas.......................................................................................................................S206

Puscar A, Orlandi A, Sequera A, Frascaroli G, Fideleff H

Po. 106 Avaliação dos pacientes com carcinoma de tireoide acompanhados no Ambulatório de Endocrinologia do Hospital das Clínicas da Universidade Federal de Goiás no período de agosto de 1995 a outubro de 2008 ...............................................................................................................................................S207

Melo APM, Albieri CD, Bueno FN, Fernandes ARGC, Jatene EM, Paula SLFM, Antunes DE, Viggiano DPPO

Po. 107 Phosphoinositide-3-kinase (PI3K) inhibition increases iodide uptake in PCCL3 cells regardless of insulin presence .................................................................................................................................................................S207

Souza ECL, Santos MCS, Braga WMO, Carvalho DP

Po. 108 Evaluación de la recurrencia del cáncer diferenciado de tiroides en grupos de bajo riesgo .............................S207 Hurtado-López LM, Melchor-Ruan J, Zaldivar RR, Basurto KE, Pulido CA, Vázquez OR, Chapa AO, Etchegaray DA, MontesdeOca E

Po. 109 Carcinoma adenoide cístico: armadilha em punção aspirativa por agulha fina em tiroide ..............................S208 De Paula EC, De Paula HM, Silva EC, Oliveira JC, De Paula GM

Po. 110 TP53 codon 72 polymorphism in thyroid nodules from Brazilian patients ..................................................................S208 De Paula EC, Reis AAS, Oliveira JC, Silva DM, Monteiro CD, Cruz AD, Saddi VA

Po. 111 Dosagem de tireoglobulina em aspirado de linfonodo cervical no seguimento do carcinoma diferenciado de tireoide: série de casos .....................................................................................................................................................S208

Bilhar FA, Batista AA, Razzolini L, Molinari AS, Azambuja Filho F, Gonçalves ICR

Po. 112 Tratamento de nódulos de tireoide por indicação estética através de alcoolização: série de casos ................S209 Bilhar FA

Po. 113 Utilidade da dosagem de tireoglobulina em aspirado de linfonodo cervical no diagnóstico de carcinoma diferenciado de tireoide quando a punção não é diagnóstica: relato de dois casos pré-tireoidectomia .............................................................................................................................................................S209

Bilhar FA, Batista AA, Razzolini L, Molinari AS, Azambuja Filho F, Gonçalves ICG

Po. 114 Microcarcinoma papilar de tiroides ¿se puede diferenciar el comportamiento agresivo inicial? ......................S210 Munizaga F, Lioi X, Hidalgo S, Munizaga C


S171

Po. 115 Nodulo intratiroideo ¿es solo de etiologia tiroidea? .....................................................................................................S210 Munizaga F, Lioi X, Rossi R, Franco C, Munizaga C

Po. 116 Carcinoma medular de tireoide com características de anaplásico ......................................................................S210 Viégas MA, Caldas G, Pinho J, Padilha M

Po. 117 Clinical and histological evaluation of 179 papillary carcinomas operated at the same Institution....................S211 Augusto GA, Shiang C, Camargo RY, Tomimori E, Ferraz A, Knobel M, Gehard R, Marui S

Po. 118 Histopathologic, prognostic and clinic features of lung metastatic papillary carcinoma of thyroid: retrospective study of 17 patients.....................................................................................................................................S211

Andrade JA, Odawara AF, Barella JLS, Villagelin D, Hanaoka N, Santos RB, Romaldini JH

Po. 119 Carcinoma papilífero é a lesão maligna mais frequentemente encontrada nos nódulos tireoideos com citologia indeterminada .........................................................................................................................................S211

Monte L, Seoane LA, Tomimori EK, Knobel M, Camargo RYA

Po. 120 Cambios bioquímicos y morfológicos durante la inhibición e involución del bocio por el 2-iodohexadecanal en tiroides de rata .....................................................................................................................S212

Thomasz L, Toro D, Oglio R, Villamar S, Fernandez M, Jahn G, Pagotto R, Pignataro O, Pisarev M, Juvenal G

Po. 121 The diagnostic value of pth concentration in the ultrasound-guided fine-needle aspiration of cervical nodules suspicious for parathyroid adenoma ...............................................................................................................S212

Seoane LA, Monte L, Tomimori EK, Knobel M, Camargo RYA

Po. 122 Lipopolysaccharide stimulates cell proliferation and modifies cell cycle-related proteins in the FRTL-5 thyroid cell line ..................................................................................................................................................S212

Nazar M, Nicola JP, Vélez ML, Pellizas CG, Masini-Repiso AM

Po. 123 Cancer papilar tiroideo con metástasis ósea vertebral asociado a paraplejía: caso clinico ..............................S213 Barberán M, Arias M, Cordero F, Liberman C

Po. 124 Arginase II and nitric oxide sintase (NOS): pathogenesis pathways of thyroid tumors ............................................S213 Sousa MSA, Latini FRM, Cerutti JM

Po. 125 Radioprotective role of 6-propyl-2-thiouracil (PTU) in thyroid cells ..............................................................................S213 Perona M, Dagrosa A, Pagotto R, Casal M, Pignataro O, Pisarev M, Juvenal G

Po. 126 Detecção da mutação BRAF em carcinoma papilífero de tiroide comparado por SSCP e PCR nested.............S214 Da Silva MJ, Fuziwara CS, Kulcsar MA, Friguglietti CU, Araujo-Filho VJF, Yoon HS, Logullo AF, Kimura ET

Po. 127 High prevalence of suspicious fine-needle aspiration cytology in thyroid nodules associated with positive thyroglobulin antibodies but not with thyroid peroxidase antibodies ........................................................................S214

Sá MBR, Villagelin D, Santos RB, Cunha M, Romaldini JH

Po. 128 Proliferacion epitelial: idetificacion de factores que aumentan el riesgo de malignidad .....................................S214 Corino M, Migliano M, Morelli S, Bacchini V, Moreno A, Padin R

Po. 129 Presentación atípica del cancer medular de tiroides (CMT) ......................................................................................S215 Herrera M, Ramos C, Veliz J, Brantes S, Villegas P, Barría M, Wohllk N

Po. 130 Peripheral thyroglobulin mRNA quantification in patients with differentiated thyroid cancer and positive anti-TG antibodies ................................................................................................................................................S215

Possato-Fernandes R, Rubio IGS, Camargo RY, Tomimori EK, Knobel M, Medeiros-Neto G

Po. 131 Factores de riesgo de falsos negativos en la punción de tiroides con aguja fina ..................................................S215 Quiroga S, De Candia L, Nebel E, Moloeznik L, Olguín M, Chiganer G, González Garcia M, Brunás O, Novelli JL

Po. 132 360 cases of differentiated thyroid carcinoma: follow-up in a single institution ........................................................S216 Assumpção LVM, Martelli V, Melo TG

Po. 133 Frecuencia de nódulo tiroideo en el Valle de México .................................................................................................S216 Hurtado-López LM, Zaldivar RR, Basurto KE, Pulido CA, Vázquez OR, Chapa AO, Etchegaray DA, MontesdeOca E,

Martinez-Duncker C

Po. 134 Thyroid cancer I131 adyuvant treatment ..........................................................................................................................S216 Pacheco OL, Martínez JA

Po. 135 An altered expression of CCR3, CCR7 and CXCR4 in papillary thyroid cancer ........................................................S217 González HE, Leiva A, Tobar H, Böhmwald K, Tapia K, Kalergis AM, Riedel CA


S172

PO. 001

Função tireoidiana em crianças e adolescentes com síndrome de Down

Monteiro SHV, Barros CJV, Imbroise R, Ribeiro MG, Beserra ICR, Guimarães MMServiços de Endocrinologia do IPPMG e do HUCFF, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

introdução: Na síndrome de Down é observada grande prevalência de doença tireoidiana (SD). De rotina é avaliada anualmente a função tireoidiana. objetivo: Avaliar a prevalência e a distribuição da doença tireoidiana em pacientes com SD, considerando a idade e sexo. Métodos: Estudo retrospectivo histórico no qual foram analisados prontuários de pacientes com SD, com diagnóstico firmado pelo Serviço de Genética. Foram excluídos pacientes com idade inferior a 4 anos, para afastar a idade de maior flutuação do TSH presente nesta síndrome. Foram anotados idade, sexo e tipo de disfunção tireoidiana. Os dados foram tratados pelo programa Epi-Info versão 3.2 e com nível de significância aceito de p valor < 0,05. Resultados: Avaliados 40 prontuários de pacientes com doença tireoidiana (22 do sexo feminino e 18 do sexo masculino) com idades entre 4,3 e 18,4 (12,2 ± 4,2). A distribuição entre os sexos foi semelhante (p = 0.33). Hipotireodismo subclínico estava presente em 32 (80%), hipotireoidismo clínico em 6 (18,7%), hipertireoidismo em 1 (0,3%) e doença nodular em outro. Neste grupo foi dosado anticorpo antitireoperoxidase em 33 pacientes e este estava positivo em novo (29%), seis destes (66,6%) apresentavam hipotireoidismo subclínico e os três restantes apresentavam hipertireoidismo, doença nodular e hipotireoidismo clínico, respectivamente. conclusão: Na SD, encontramos uma prevalência elevada de hipotireoidismo subclínico, em sua maioria não relacionada à doença autoimune da tireoide.

PO. 002

Absence of PAX-8 and TSH receptor genes mutations in patients with thyroid dysgenesis

Brust ES1, Beltrao CB1, Chammas MC2, Juliano AG2, Watanabe T2, Sapienza MT2, Marui S1

1Laboratório de Endocrinologia Celular e Molecular, Unidade de Tireoide, LIM 25; 2Departamento de Radiologia, Inrad, Hospital das Clínicas, Faculdade de Medicina da Universidade de Sao Paulo; Sao Paulo, Brazil

Thyroid dysgenesis is the most common cause of congenital hypothyroidism (CH), including athyreosis, hemiagenesis, hypoplasia and ectopia1. PAX-8 has important role in thyroid development and migration and mutations were found in ectopia and hypoplasia2. As TSH is responsible for follicular growth and differentiation, TSH-receptor (TSH-R) mutations were found only in hypoplasia3. objective: Search for mutations in PAX-8 and TSH-R in thyroid dysplasia. Methods: We evaluated 40 patients with CH from APAE-São Caetano-Brazil. Dysgenesis was diagnosed using color-Doppler ultrasound (CDUS), radioactive iodine uptake scan and thyroglobulin levels (TG). We defined athyreosis when no thyroid image was detectable with undetectable or low TG. Hypoplasia was defined by CDUS as total volume < 2 SD according to available age, gender, height or body surface references. DNA was extracted from peripheral leukocytes. Coding region and exon-intron boundaries were amplified and directly automatic sequenced. We evaluated PAX-8 from ectopia, athyreosis and hypoplasia and TSH-R from hypoplasia. Results: We studied 29 and 13 patients for PAX-8 and TSH-R, respectively. We diagnosed 13 patients with ectopia; all located at submentum region, with TG from 12.2-123 ng/dL. We defined 10 hypoplasia with TG from 6.8-65.2 ng/dL; 3 athyreosis with undetectable TG and 3 with TG rom 4- 9.1 ng/dL. We did not find PAX-8 and TSH-R mutations in our cohort. We only found homozygous polymorphism previously described in TSH-R (Glu728Asp) in 2 athyreosis and 2 hypoplasia. conclusions: Mutations in PAX-8 and TSH-R are extremely rare and other genetic or environmental factors must be involved in thyroid dysgenesis etiology.

PO. 003

Densidad mineral osea y anticuerpos al receptor de TSH en enfermedad de Graves postratamiento: premenopausia versus posmenopausia

Ercolano M, Drnovsek M, Silva Croome MC, Moss M, Fuentes A, Viale F, Gauna A, Laguna J, Antonovic GDivisión Endocrinología, Hospital Ramos Mejía, Buenos Aires, Argentina

En mujeres eutiroideas con antecedente de hipertiroidismo por Graves (EaHG), observamos menor densidad mineral ósea (DMO) en columna y cuerpo entero C-E sólo en posmenopausia-en relación a respectivos controles. Fueron referidos receptores de TSH en osteoblastos y correlación positiva entre marcadores óseos y TRAb. objetivos: Evaluar la relación de parámetros clínicos y TRAb con DMO en pacientes EaHG premenopausicas vs. posmenopáusicas. Material y metodos: 57 pacientes EaHG, con o sin T4, evaluadas en premenopausia (n = 30) vs. posmenopausia (n = 27), sin factores que alteren metabolismo óseo. Evaluamos: Calcemia, T4, TSH, TRAb, Z-score-L2-L4, cuello de fémur y C-E (DPX-Lunar). estadística: Mann-Whitney-test, Exacto de Fisher, correlación Spearman y Regresión Múltiple. Resultados: En premenopausia, tiempo de evolución de enfermedad (TEE) y de eutiroidismo fueron menores que en posmenopausia (p < 0.007), con similar tiempo de hipertiroidismo, factores de riesgo de osteoporosis, calcemia y parámetros tiroideos. El Z-score fue menor en L2-L4 y C-E en posmenopausia vs. premenopausia (0.11 + 0.19vs-043 + 1.03,p < 0.05 y 0.24 + 0.91vs–08 + 1.03,p < 0.05). En posmenopausia Z-score-L2-L4 correlacionó con TRAb (R = -0.53, p < 0.008) y TEE (R = 0.42,p < 0.03); TRAb correlacionó con TEE (R = -0.45, p < 0.02). En análisis de regresión múltiple, sólo TRAb correlacionó con Z-score-L2-L4 justificando el 37.7% de variación de DMO. En premopausia no hubo ninguna correlación con DMO. conclusiones: Las pacientes EaHG: 1) evaluadas en posmenopausia vs. premenopausia a) presentaron mayor TEE a expensas de mayor tiempo de eutiroidismo y b)menor Z-score en C-E y L2-L4. 2) En las posmenopausicas el Z-score-L2-L4 correlacionó con TRAb y TEE. El TRAb fue la única variable independiente en relación a DMO en raquis, avalando una relación del TRAb con DMO independiente de la función tiroidea.

CliniCal Thyroidology

Abstracts – poster presentation

S173

PO. 004

Long term follow up of congenital hypothyroid patient due to IVS30 + 1G > T mutation which promote endoplasmic reticulum enlargement and altered expression of specific thyroid genes

Galrão AL1, Rubio IGS1, Pardo V1, Knobel M1, Possato RF1, Camargo RRY1, Ferreira MA2, Kanamura CT3, Gomes AS, Medeiros-Neto G1

¹Thyroid Unit (LIM-25), Division of Endocrinology, University of São Paulo Medical School, São Paulo, Brazil. ²Cell Biology (LIM59), Division of Pathology, University of São Paulo Medical School, São Paulo, Brazil. ³Adolfo Lutz Institute, São Paulo Public Health Service, São Paulo, Brazil. 4Division of Endocrinology, Federal University of Sergipe Medical School, Aracaju, Brazil.

Background: Congenital hypothyroidism is the most common endocrine disease in childhood. Thyroglobulin (TG) gene inactivating mutations have been identified and characterized in association with congenital goiter and hypothyroidism. objectives: To report the 11-years follow up of a patient harboring IVS30 + 1G > T TG mutation and to performed molecular and microscopy analysis of the affected thyroid tissue. Patients and methods: A 18 yrs patient with neonatal goiter and severe congenital hypothyroidism diagnosed at the 3 yrs when LT-4 treatment was started. Nodular and non-nodular thyroid tissue specimens were collected after thyroidectomy. Expression of specific thyroid genes was evaluated by real-time PCR and protein localization by immunohistochemistry. Results: In non-nodular and nodular tissue samples, TG, TSHr, TPO, PDS, PAX8, TTF1 and NIS mRNA were reduced compared with normal thyroid tissue. Low expression of PDS, similar expression of PAX8 and TTF1, and higher expression of TG, TSHr, TPO e NIS were detected in nodular as compared to non-nodular tissue. Microscopic evaluation showed enlarged follicular lumen and swollen vesicles of endoplasmic reticulum in nodular and non nodular samples. Strong cytoplasmic and low follicular lumen TG immunostaining were detected in both tissues. Intracellular NIS, membrane TPO and TSHR immunostaining had higher positivity in non-nodular tissues. The patient had a long-term adequate developmental outcome (height 1.76 m), despite treatment delay. conclusions: The IVS30 + 1G > T mutation leads to endoplasmic reticulum enlargement and altered expression of specific thyroid genes. The favorable clinical outcome of patients harboring this mutation supports the hypothesis that environmental influences (iodine nutrition) have an impact on the final phenotypic appearance. Support: FAPESP, Indatir.

PO. 005

Manifestações raras em doença de Graves: relato de caso

Sacramento Monte RS, Guedes DSN, Perez A, da Cunha AMF, Soares DVServiço de Endocrinologia, Hospital dos Servidores do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

A doença de Graves (DG) se caracteriza por uma da tríade clássica: hipertireoidismo, bócio difuso e oftalmopatia infiltrativa e pode cursar com outras manifestações menos comuns. Relatamos o caso de um paciente com DG associado a duas manifestações raras, pancitopenia e hiperpigmentação em membros inferiores (MMII). POC, masculino, 34 anos, DG há 6 anos, tratamento irregular com antitireoidianos. Ao exame bócio difuso, taquicardia e hiperpigmentação no terço distal dos MMII. Exames: Hto: 22,6% Hb: 7,9 g/dl, leucócitos 1.900, plaquetas 10.300, TSH: 0,03 uiU/ml, T4L > 6,0 ng/dl, TRAb: 65%. Ferritina, vit B12 e ácido fólico níveis normais. Teste de Coombs direto e indireto positivos sugerindo anemia hemolítica. Biopsia de medula óssea: hiperplasia eritroide na medula óssea. Terapia imunossupressora (prednisona 1 mg/kg/dia) por 20 dias resultou em melhora discreta da anemia. O pacientes, recebeu 15 mCi de radioiodo e, após atingir o eutireoidism,o ocorreu normalização da contagem de leucócitos, hemácias e plaquetas. Concomitante, apresentou melhora da hiperpigmentação de MMI. As manifestações hematológicas na DG variam desde anemia ou leucopenia isoladas até pancitopenia. Essas alterações podem estar associadas tanto a outras doenças autoimunes concomitantes como ser desencadeadas diretamente pelo hipertireoidismo. Além disso, um quadro raro de hiperpigmentação pode se relacionar com hipertireoidismo de longa data não tratado (alteração dermatológica conhecida como hiperpigmentação addisoniana). Brent GA. Graves’ Disease. N Engl J Med. 2008; 358;24-2594-5; Lima CSP, et al. Pancytopenia in untreated patients with Graves’ disease. Thyroid. 2006;16 (4); Ford HC, et al.The hematology of hyperthyroidism:abnormalities of erythrocytes, leucocytes, thrombocytes and haemostasis. Postgraduate Medical J. 1988;64:735-42.

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In vivo efects of triiodothyronine (T3) on mouse B lymphocytes

Bloise FF1, Cordeiro A1, Mello-Coelho V2, Rumjanek V3, Pazos-Moura C3

1Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro; 2Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brazil

Background: Thyroid hormones are critical to regulate differentiation, growth, metabolism and immune function, although their effects on the physiology of lymphoid organs are still not well elucidated. Objective: To investigate T3 effect on lymphocytes of spleen and mesenteric lymph nodes of mice. Methods: Young C57/Bl6 males and females mice were treated with T3 (5 µg/10g body weight) during 15 days or saline (control; C). Results: Primarily we analyzed the weight and cellularity of each organ. T3-treated males presented an increase in the weight of the spleen (C: 76 ± 5 mg, T3 147 ± 8 mg; p < 0,0001) however, there were no significant differences on lymph nodes weight (control 40 ± 5 mg, T3 50 ± 9 mg). T3-treated females had an increase in the spleen weight as well (C: 68 ± 2 mg, T3: 100 ± 7 mg; p = 0,0006), but showed only a trend to a lower lymph nodes weight (C: 41 ± 6 mg, T3: 34 ± 2g). We analyzed by flow cytometry the subtypes of lymphocytes, T lymphocytes (helper and cytotoxic cells) and B lymphocytes populations of the spleen and lymph nodes. There were no differences in the T lymphocytes population (neither helper nor cytotoxic) in spleen nor in lymph nodes of the mice treated with T3 compared to controls. However, flow cytometry analysis showed a 10% reduction in splenic B lymphocyte population in the males (p = 0,026) treated with T3 in relation to the control. The same trend was observed in the females although the effect was not significant. conclusions: Our data showed that induction of hyperthyroidism by T3 treatment interfered with splenic physiology, promoting a reduction on resident B lymphocytes, without significant alterations on T lymphocytes populations.


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Avaliação ultrassonográfica da tireoide, determinação da iodúria e concentração de iodo em sal de cozinha utilizado por escolares de Ribeirão Preto, São Paulo, Brasil

Alves MLD1, Duarte GC2, Navarro AM1, Tomimori EK2

1Curso de Medicina da Universidade de Ribeirão Preto, Brasil; 2Disciplina de Tiroide – Hospital das Clínicas da Faculdade de Medicina de São Paulo, Brasil

Estudo realizado em 2003 mostrou 78,06% das iodúrias acima de 300 µg/L e prevalência média de 14,15% de bócio, pelo método palpatório, entre escolares de Ribeirão Preto, São Paulo. Após mudanças governamentais na política de iodação do sal de cozinha utilizado pela população brasileira, reavaliamos o volume tireoidiano por ultrassonografia e a ingesta iódica de 300 escolares de ambos os sexos, entre 8 e 10 anos de idade, em três diferentes escolas públicas desse município, as mais representativas de classes socioeconômicas distintas A = mais elevada (98 crianças), B = intermediária (84) e C = mais baixa (118). O exame ultrassonográfico foi realizado por equipamento Aloka, iodúria pelo método de Sandll-Kolthoff e dosagem de iodo em amostras de sal de cozinha por titulação. Observou-se aumento progressivo nos volumes tireoidianos entre as meninas com o avançar da idade, podendo esse fato estar relacionado à maturação puberal mais precoce no sexo feminino. As iodúrias medianas foram maiores entre as crianças da escola A que as da escola B e que as da C e essas diferenças foram estatisticamente significantes. As concentrações de iodo em sal de cozinha foram progressivamente mais elevadas da escola C para a B e A.

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Hypothyroidism presented as slipped upper epiphysis, hydrocele, short stature and hypogonadism

Lauand TCG, Santana CM, de Sousa PB, Marques ELV, Pedrosa HCEndocrine Division, Hospital Regional de Taguatinga, Governo do Distrito Federal, Brasília, Brazil

Background: The full-blown expression of hypothyroidism is known as myxedema. The disease affects mainly middle aged women. objective: A case of hypothyroidism presented as a slipped upper epiphysis, hydrocele, short stature and hypogonadism. Methodology: Medical report review and web data survey. Results: Case report – A nineteen year old male patient who searched for medical assistance due to short stature and absence of sexual characters development until then. After some months of limb pain complaints without previous trauma he was diagnosed with bilateral femoral slipped upper epiphysis and further referral to an endocrine evaluation for short stature and hypogonadism. The neurological and motor development was appropriated but under weight was noticed (59 kg, z score: -0,3), height was 144cm (z score: -3,9) and no secondary sexual characters were registered. Bilateral hydrocele was confirmed by ultrasound. X-ray showed bone age to be 12 years. The diagnosis of primary hypothyroidism was confirmed by a THS: 1339,1 mcUI/ml, thus levothyroxine treatment was initiated. conclusions: A few previous reports have mentioned hydrocele as the only serous effusion found in hypothyroidism. The pathogenesis of slipped upper femoral epiphysis is still unknown but there is evidence of its association with various endocrine disorders. Therefore, it’s advised to investigate such a condition in the presence of bilateral slipping, obesity and short stature. References: Puri R, et al. Slipped upper femoral epiphysis and primary juvenile hypothyroidism. J Bone Joint Surg Br. 1985;67(1):14-20; Isaacs AJ, et al. Myxoedema and hydrocele. Br Med J. 1976;1 (6005):322.

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Treatment of Graves’ ophthalmopathy with an antagonist of PPAR-gamma: preliminary results

Bloise W, Mimura LY, Moura J, Nicolau WGraves’ Ophthalmopathy Section-Thyroid Unit-Hospital das Clínicas-School Medicine of Sao Paulo, Sao Paulo, Brazil

Expression of PPAR-gamma (Pg) is significantly increased in the orbital fibro-adipose tissue of active Graves’ ophthalmopathy (GO). Agonist use of Pg was considered in developing or worsening GO. objective: The aim of this preliminary report is to evaluate the use of an antagonist of the Pg in the treatment of selected GO. Methods: Eleven patients without ocular treatment 3 months before the inclusion in this research and classified by (CAS) index between 2 to 5 from 27 to 68 years old (mean 43.8 ± 13.9), 6 females were selected. Five patients had hyperthyroidism and 3 had hypothyroidism and 3 euthyroidism The GO duration ranged from 4 to 60 months (mean 29.8 ± 19.04). Ocular muscle restriction was evaluated by scores from 0 to 4. Sodiun Diclofenac an antagonist of Pg was administered orally 50 mg every 12 hours for 5.4 ± 2.6 months. Blood counts and renal function were checked during the treatment. Ointments and lubrication drops were administered to all patients. Results: Ocular pain vanished in 5 of 6 patients.Diplopia disappeared in 2 of 4 individuals and improved in 1. The mean of the total muscle restriction scores decreased not significantly from 4.91 ± 3.42 to 3.25 ± 3.84. Proptosis unchanged: right eye: 23.3 ± 3.3 to 23.0 ± 3.1 and left eye 23.5 ± 3.1 to 23.2 ± 3.2.The small improvement of the CAS index was not significant: 2.72 ± 1.27 and 2.27 ± 0.9 before and after treatment. Only one patient complained of resistant gastric pain relieved by increasing omeprazol dosage. conclusion: The excellent improvement of ocular pain and less pronounced relief in diplopia and CAS index if confirmed in a greater number of patients may be a safer and less expensive treatment to these unconfortable symptoms of GO and avoid the many adverse effects of orbital radiotherapy or oral corticoid.


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Exoftalmometria y apertura palpebral en adultos mexicanos

Flores-Rebollar A1, Navarro-Lara A1, Moreno-Castañeda L1, López-Carrasco G2, Montaño-Lechuga MC2, Ruiz-Juvera A2, Sepúlveda-Méndez J2, Natera-Cruz E3, González-Treviño O2

1Dpto. de Medicina Interna; 2Medicina Nuclear; 3Oftalmología; del Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, México, DF

El exoftalmos es una de las manifestaciones clínicas más impactantes de la enfermedad de Graves, la actividad clínica y estratificación de alguna de las escalas más utilizadas en la oftalmopatía de Graves utilizan la exoftalmometría y la evolución de la apertura palpebral. Son conocidas las diferencias raciales en la proptosis, por tal razón decidimos estudiar a nuestra población. sujetos y metodos: El estudio se realizó en 278 individuos voluntarios sano, sin antecedentes de enfermedad tiroidea, con exploración tiroidea normal, así como TSH y T4L normales; 123 hombres y 155 mujeres, con una edad promedio de 28.47 ± 8.2 años (17-67 años, mediana 26 años). La exoftalmometría se realizó con un exoftalmómetro de Hertel por un mismo investigador, la apertura palpebral con una regla métrica transparente; ambas mediciones de acuerdo a las recomendaciones del grupo European Group Graves’Orbitopathy (EUGOGO). Resultados: La proptosis promedio de ambos ojos en el hombre fue 14.41 ± 1.74mm (IC 95% 10.93-17.89), Ojo derecho 15.05 ± 1.70mm y Ojo izquierdo 13.90 ± 1.71mm. La proptosis promedio de ambos ojos en la mujer fue 14.33 ± 1.83 (IC 95% 10.67-17.99), Ojo derecho 15.01 ± 1.86mm y Ojo izquierdo 13.66 ± 1.90mm. El promedio de apertura palpebral en ambos ojos en el hombre fue 8.56 ± 1.43mm y en la mujer fue de 9.14 ± 1.64mm. conclusiones: Nuestros resultados muestran diferencias con otros estudios similares, y encontramos el promedio más bajo de proptosis, comparada a razas caucásica y negra e incluso al único estudio realizado previamente en México, de este último registramos la misma diferencia de tamaño entre el OD y el OI, este último más pequeño.

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Avaliação da função muscular, tolerância ao exercício, capacidade funcional e aspectos clínicos no hipertireoi-dismo subclínico

Chachamovitz DSO1, Jerusalmi ALC1, Vigário PS1-2, Cordeiro MFN1, Castro CLN3, Vaisman M1, Teixeira PFS1

1Departamento de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro; 2Labofise, Escola de Educação Física e Desportos, Universidade Federal do Rio de Janeiro; 3Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

O presente estudo tem por objetivo avaliar se no hipertireoidismo subclínico (HSC) existe maior prevalência de alterações da força e fadiga muscular. Métodos: Estudo seccional, com dados de pacientes com HSC induzido por terapia supressiva com levotiroxina para carcinoma diferenciado de tireoide (TSH < 0,4 µUl/ml; T4L: 0,8 a 1,9 ng/dL), comparando os resultados aos de pacientes eutireoidianos. Foram avaliadas: força de quadríceps (FQ) isométrica através de dinamômetro de cadeira extensora (kgf), força de preensão (FP) palmar através do dinamômetro de Jamar, fadiga de quadríceps e palmar através da mensuração do tempo redução em 50% da força máxima e fadiga escapular através de repetições da elevação vertical do braço (alteres de 1 kg) com metrômetro de 40 rep/min. Resultados: Vinte e um pacientes com HSC e 10 controles foram incluídos. A FQ, corrigida para sexo, idade, peso e altura, não diferiu entre os grupos. Fazendo-se análise multivariada observa-se que a FP não difere entre os grupos quando idade, sexo e sedentarismo são considerados. Observamos uma tendência a maior fadiga na força de preensão e de quadríceps no HSC, sem significância estatística para a força de preensão (p = 0,123), porém significativa para força de quadríceps (152 vs. 83 seg; p = 0,026), mesmo controlando para sedentarismo. Para fadiga escapular, analisando-se somente as mulheres sedentárias, o tempo para fadiga da cintura escapular é menor no HSC: 73,5 seg vs. 29,2 seg no HSC (p < 0,05). conclusão: Apesar de não associar-se à redução de força muscular, o estudo sugere que HSC está associado à maior fadigabilidade muscular ao esforço.

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Madre hipoparatiroidea e hipotiroidea y recien nacido

Falcón-de-Legal E, Menoni-de-Lezcano MServicio de Endocrinología y Metabología; Hospital Central, Instituto de Previsión Social, Asunción, Paraguay

Reporte de caso: Paciente femenino 34 años, sometida a tiroidectomía total por bocio multinodular 3 años atrás, con consecuencias de hipoparatiroidismo secundario. En el inicio fue de difícil control. Por causa de esto, fueron realizadas varias combinaciones de calcio con vitamina D y Magnesio. Pasados 2 años de tratamiento con levotiroxina sódica, carbonato de calcio y alphacalcidol, la paciente quedo embarazada. Para lograr un embarazo exitoso fue necesario ajustar la dosis de calcio y vitamina D, asi como la levotiroxina. Fueron realizados monitoreo regular de la calcemia, fosfatemia y el TSH, además de las rutinas normales solicitadas propias para una gestante. Asimismo, fue acompañada regularmente con ecografía fetal, demostrando feto con buena vitalidad y dentro de los parámetros normales. Se llevó a término la gestación con Levotiroxina 175 mcg/dia; lactato de calcio 2 gr (formulado) 3 veces al día y Alphacalcidol 0,25 mcg 2 veces al día; Magnesio (carbonato de magnesio 198,81 mg y sulfato de magnesio 321 mg) 2 veces al día; Sulfato ferroso (medicamento orientado por el ginecólogo). El parto fue normal y el recién nacido sin efectos adversos del uso de vitamina D. Conclusión: Aunque la escasa bibliografía disponible no presenta una fuerte recomendación sobre los efectos del hipoparatiroidismo materno en el recién nacido, nuestra experiencia sugiere que el tratamiento adecuado y oportuno de la madre y el monitoreo constante del calcio y fósforo pueden reducir el daño en el neonato.


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Evaluation of quality of life in patients with Graves disease treated with methimazole and radioiodine – preliminary results in a small population

Corralo GCMB1, Villagelin D1-2,Santos RB1, Cunha M1, Malouf EZ1, Romaldini JH1-2

1Departament of Endocrinology, Pontifícia Universidade Católica de Campinas; Campinas, Brasil; 2Hospital Servidor Publico Estadual; Sao Paulo, Brasil

Background: Antithyroid drugs (ATD) and radioiodine (RAI) are used for treatment of hyperthyroidism due to Graves’ disease (GD) but there is little information of the kind of treatment modality respect to quality of life. objective: Evaluate the quality of life in GD patients following ATD compared to RAI treatment. Patients: A total of 38 GD patients were included in the study. Twenty-four patients (median age 37 yr, 14-87 yr) were on continuous low ATD for 46.5 months (18-67 months) and 14 patients (37 yr, 17-67 yr) received a fixed dose of 15 mCi and were followed-up for 34 months (10-120 months). Measurement: The patients underwent measurement of a 36-item short form health status survey questionnaire, when were in euthyroid state. The SF-36 evaluates eight parameters: functional capacity, limitation for physical aspects, pain, general health status, vitality social aspects, limitation for emotional aspects and mental health. The statistical analyses used were the Kruskal-Wallis analysis of variance (ANOVA) by ranks and the Mann Whitney test. Results: The SF-36 measurement was slight worse (p < 0.0001) in RAI-treated patients and had a lower functional capacity (p < 0.0001) than in patients on ATD treatment. conclusion: Both treatment ATD and RAI improve the quality of life but our data indicate that there was a strong trend for RAI-treated patients for lower quality of life aspects.

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Audiologic evaluation in patients with acquired hypothyroidism

Santos KTP, Martins RHG, Dias NH, Lapate RL, Carvalho LR, Mazeto GMFSDepartment of Otorhinolaryngology, Ophthalmology and Head and Neck Surgery and Department of Internal Medicine, Botucatu Medical School, Sao Paulo State University, Botucatu, Brazil

Background: Hypoacusis associated with hypothyroidism has been investigated by numerous authors. However, the physiopathology, risk co-factors and lesion sites are still dubious. objectives: To investigate hearing acuity, cochleovestibular symptoms and correlated factors in patients with acquired hypothyroidism. Methods: We created two groups: sample group (SG, n-30), patients with acquired hypothyroidism and a control group (CG, n-30), of healthy volunteers. characteristics of interest: age, gender, time since the diagnosis of hypothyroidism, comorbidities, cochleovestibular symptoms, biochemistry and hormonal tests (TSH, unbound T4), audiometry, transient evoked otoacoustic emissions (TEOAE) and brainstem evoked auditory potentials (BEAP). Results: Cochleovestibular symptoms were more frequent in the SG (76.7%) when compared to the CG (26.7%), and hypoacusia, tinnitus and vertigo prevailed. Fasting glucose values were higher in 40% of the SG and in 10% of the CG. In 22 ears from the SG and seven from the CG the hearing thresholds were higher, characterizing mild sensorineural hearing loss. The BEAP was altered in 10 ears from the SG and in none from the CG, stressing LAV (Wave V Absolute Latency) prolongation. The TEOAE were absent in 12 ears from the SG and in four from the CG. conclusions: cochleovestibular symptoms were more frequent in patients with hypothyroidism. They also had a larger number of altered auditory exams, with 3 higher audiometric thresholds, causing mild sensorineural hearing loss, LAV prolongation and absence or reduction in TEOAE amplitudes. Such alterations are not associated with serum levels of the biochemical or hormonal tests.

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Comparison of different doses of radioiodine in severe Graves hyperthyroidism: a clinical trial with historical control

Dora JM, Machado WE, Andrade VA, Maia ALThyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

Background: Radioiodine (131I) has become a first line treatment in Graves’ disease (GD), but failure occurs in ~15-25% of cases. We have previously shown that large goiter is an independent predictor of treatment failure1. These patients usually present severe hyperthyroidism with very high serum T3 levels ( > 500 ng/ml) and high 24h radioiodine uptake (24h-RAIU, > 90%). It is generally accepted that higher doses of 131I improve cure rates and a recent meta-analysis showed a correlation between 131I dose and successful 131I therapy in GD patients2. objectives: To evaluate whether higher doses of 131I increases the efficacy of treatment in severe GD. Methods: Patients with GD and goiter ≥ 48ml are eligible to study entry. In the contemporaneous intervention cohort patients are treated with 250 µCi of 131I/ml thyroid tissue, corrected by 24h-RAIU (Group 1). A subgroup of patients with GD and goiter ≥ 48 ml treated with 200µCi of 131I/ml/24-RAIU, from our previous study1, serves as a historical control (Group 2; n = 15). The primary outcome evaluated was cure at one year. Fourteen patients were assigned to receive 250 µCi of 131I/ml/24-RAIU. Results: There were not significant differences between the two treatment groups at baseline (age, gender, tabagism, BMI, pre-treatment with metimazole, thyroid volume or thyroid hormone levels). The cumulative cure rate in patients from Group 1 at 6 months was 76.1%, similar to that observed in Group 2 (60.0%; p = 0.61). conclusions: Our results suggest that administration of higher doses of radioiodine does not improve cure rates in severe GD. References: JCEM. 2001; 86:3488; BMJ. 2007; 334:514.


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Etiologias do hipotireoidismo congênito na região de Ribeirão Preto – São Paulo – Brasil em crianças nascidas entre 1994 e 2005

Magalhães PKR, Maciel LMZDivisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto; Ribeirão Preto, Brasil

introdução: As principais etiologias do hipotireoidismo congênito (HC) relatadas na literatura internacional são as disgenesias (70-80%) e os defeitos de síntese (10%-15%). objetivos: Avaliar as etiologias do HC nas crianças triadas no Centro de Referência em Triagem Neonatal de Ribeirão Preto no período de 1994 a 2005. Métodos: Foram convocadas para avaliação clínica e laboratorial todas as crianças com TSH neonatal ≥ 10 µU/ml colhido após 48 horas de vida. A cintilografia tireoidiana foi incluída na avaliação inicial para elucidação etiológica. Crianças com tireoide tópica foram reavaliadas aos 3 anos de idade, após a suspensão do tratamento por 1-2 meses e realizado o teste do TRH (7-10 µg/kg/EV) nas crianças com TSH entre 5–15 µU/ml (resposta normal: pico TSH < 35 µU/ml). Foram excluídos os recém-nascidos com idade gestacional abaixo de 37 semanas. Resultados: Neste período foram realizados 197.265 testes de triagem neonatal, sendo detectadas 130 crianças com TSH confirmatório no soro > 4 µU/ml. Destas 22 (16,9%) apresentaram ectopia, 8 (6,1%) agenesia, 3 (2,3%) hemiagenesia/hipoplasia, 34 (26,1%) defeitos de síntese e 4 (3%) com etiologia não definida. Em 37 crianças (28,5%), houve normalização das concentrações do TSH sérico (HC transitório). Dez (7,7%) perderam o seguimento e 2 (1,5%) foram a óbito. Seis crianças (4,6%) mantêm o TSH entre 5-10 µU/ml e ainda não realizaram o teste do TRH. Quatro crianças (4%) persistem com TSH discretamente elevado e apresentaram teste do TRH normal. conclusões: Considerando o nível de corte adotado, a incidência do HC por defeito de síntese é semelhante à das disgenesias tireoidianas e a do HC transitório é elevada, salientando a importância da reavaliação etiológica aos 3 anos de idade.

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Avaliação da função e da auto-imunidade tireoidianas em mulheres acima de 35 anos, infectadas pelo HIV

Carvalho LG, Vaisman M, Barroso PF, Panico ALBG, Teixeira PFSServiço de Endocrinologia e Serviço de Doenças Infecto-Parasitárias (DIP), Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (HUCFF); Rio de Janeiro, Brasil

introdução: Doenças autoimunes tireoidianas estão entre as principais causas de disfunção tireoidiana. Na cidade do Rio de Janeiro, detectou-se 10% de positividade para anticorpo antitireoperoxidase em mulheres acima de 35 anos e de 12,3% e 3,5% de hipo e hipertireoidismo, respectivamente. O surgimento destas e de outras doenças autoimunes em pacientes HIV positivo tem sido estudado, principalmente em pacientes em uso de terapia anti-retroviral (TARV), como consequência da chamada síndrome de reconstituição imune. objetivo: Avaliar a prevalência de disfunção e autoimunidade tireoidianas em mulheres acima de 35 anos, HIV positivo. Métodos: Estudo seccional, no qual foram medidos TSH, T4 livre, anti-TPO, carga viral e CD4 de 56 mulheres acima de 35 anos, HIV positivo, acompanhadas no ambulatório de DIP do HUCFF, excluindo-se as com internações nos últimos dois meses. Resultados: As frequências de positividade de anti-TPO e de TSH elevado (hipotireoidismo subclínico) foram de 3,6% no grupo total e de 4,5% no grupo das pacientes que usam TARV. A frequência de TSH baixo ( < 0,01 µI/ml) foi de 6,4% no grupo total de pacientes e de 6,8% nas que usam TARV. conclusões: Esses resultados preliminares não demonstram maior frequência de positividade de anticorpos antitireoperoxidase em mulheres HIV positivo em uso de TARV, porém sugerem uma maior prevalência de hipertireoidismo, havendo a necessidade de se aumentar a casuística e estudar a presença de TRAB circulante nas mesmas, pela possibilidade de associação com maior prevalência de doença de Graves nessas pacientes.

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TSHoma: desafio diagnóstico – relato de caso

Muniz TZ, Ourdakian MK, Fernandes LPSDisciplina de Endocrinologia, Departamento de Clínica Médica da Universidade de Marília (Unimar); Marilia, Brasil

introdução: TSHoma é uma causa rara de hipertireoidismo, com prevalência de 1:1 milhão. A maioria dos pacientes se apresenta com sintomas de hipertireoidismo associado a bócio e sintomas compressivos causados pelo adenoma hipofisário produtor de TSH. objetivo: Relatar um caso de TSHoma em paciente assintomático. Relato de caso: JLR, masculino, caucasiano, 35 anos, procurou serviço por alterações da função tireoideana observadas após exames de check-up. Negava alterações sugestivas de tireotoxicose, alterações visuais ou cefaleia e apresentava níveis persistentemente elevados de T4 livre e T3 livre, porém com TSH apresentando-se com valores normais nos exames dos últimos 14 meses. Negava medicações e seus antecedentes pessoais e familiares não eram significativos. Apresentava tireoide discretamente aumentada, ausência de exoftalmo ou sinais de tireotoxicose. exames: TSH: 5,5 (VR- 0.40–4,0) mU/L, T4 livre: 2,2 (VR: 0,8–1,9) mcg/dl e T3 livre:27.5 (VR: 1,5-4,1) pg/ml. TSH subunidade-: 1.9 ng/mL (normal < 1.0), relação molar subunidade-:TSH (subunidade- x 10/TSH): 1.55 (normal < 1) teste de TRH aumento > 2 x. A RNM de hipófise evidenciou adenoma hipofisário de 5 mm x 2 mm x 5 mm. conclusão: A maioria dos pacientes com hipertireoidismo e níveis elevados de T4 e T3 possui níveis indetectáveis de TSH. Raramente, pacientes podem apresentar níveis inapropriadamente normais ou níveis elevados de TSH (secreção inapropriada de TSH) que caracteriza um desafio diagnóstico. Síndrome de resistência ao hormônio tireoideano e outras causas de confusão como elevação da TBG, hipertiroxinemia familiar disalbuminêmica e anticorpos contra TSH, T4 ou T3 devem ser excluídas.


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Pseudotumor inflamatório de órbita: um diagnóstico diferencial de oftalmopatia de Graves

Caminha LSC, Rebelo E, Sousa PAM, Oliveira RA, Buesco A,Vaisman MDepartamento de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

introdução: A causa mais comum de exoftalmia, mesmo unilateral, é oftalmopatia de Graves. objetivo: Apresentar e discutir uma causa rara, inflamatória, de exoftalmia. Relato de caso: Feminina, 39 anos, iniciou acompanhamento em 2000, por proptose unilateral. Ao exame, apresentava proptose à direita, edema periorbitário, eritema conjuntival; motilidade ocular normal, sem dor, diplopia ou bócio. Laboratório mostrava eutireoidismo, anticorpos anti-TPO e antitireoglobulina negativos. A tomografia computorizada de órbitas evidenciou aumento da densidade de gordura orbitária e do volume do músculo reto lateral maior à direita; ultrassonografia com aumento da densidade de gordura bilateral mais acentuada à D. Iniciado pulsoterapia com metilprednisolona, seguida de prednisona (total de 12 meses) com resolução do quadro. Permaneceu assintomática de 2001 a 2007. Em março de 2008, apresentou leve proptose, desta vez à esquerda, com edema periorbitário. TC e RM de órbitas revelaram discreta proptose a E, secundário à formação expansiva intraconal que acompanha o trajeto do nervo óptico. Musculatura extrínseca e gordura periorbitária sem alterações. Mantinha eutireoidismo, anti-TPO e TRAB negativos. Biópsia da lesão orbitária: infiltrado inflamatório crônico; amostra de tecido muscular normal. Firmado diagnóstico de pseudotumor inflamatório de órbita e iniciado pulsoterapia, devido à piora do quadro. Melhora dos sinais inflamatórios e da proptose nas primeiras 24 horas após o pulso. conclusão: Pseudotumor inflamatório de órbita é uma condição incomum, de causa desconhecida, sendo a terceira causa de tumor primário de órbita. Mimetiza clínica e radiologicamente neoplasias e outras condições inflamatórias. Possui caráter recidivante e a resposta à corticoterapia é um dos critérios diagnósticos.

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Human DuOx 2 promoter activity regulation by hormones and transcripition factors

Cardoso LC1, Querino AL1, Costa MEWF2, Carvalho DP1, Santisteban P3

1Laboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; 2Laboratório de Biologia Molecular e Bioquímica de proteínas, IBCCF, UFRJ; Rio de Janeiro, Brazil; 3Instituto de Investigación Alberto Sols, Universidad Autónoma de Madrid, Madrid, Spain

Background: Mutations in DuOx 2 gene have been associated with hypothyroidism due to the presence of a truncated protein unable to produce sufficient amounts of H2O2. Studies on the regulation of thyroid DuOx 2 promoter activity are important to further elucidate the pathways involved in thyroid H2O2 production linked to hormonogenesis. objectives: Our aim was to study thyroid DuOx 2 promoter activity regulation by hormones and transcription factors (TF). Methods: A DNA fragment containing DuOx 2 promoter region (0.6 kbp DNA fragment) was transfected in thyroid and non-thyroid cells. PCCL3 cells were cultivated in Coons F-12, containing 0.2% FBS (starvation medium) for 72 h. TSH (1 nM ou 2 nM), insulin (10 ng/ml), IGF-1 (100 ng/ml) and forskolin (10 µM) were added to the culture medium for 24 h. HELA and HEK cells were cultivated in DMEN medium containing 10% FBS. Cells were collected 24 hours after transfection for the measurement of luciferase and renilla activities. Results: DuOx 2 promoter activity was positively regulated by cAMP, insulin and IGF-1 in PCCL3. TTF-1 e PAX 8 increased DuOx 2 promoter in HeLA and HEK. CREB and DREAM together were able to increase DUOX 2 promoter activity in HeLA. NKX 2.5 is expressed in thyroid progenitor cells, but it is no longer expressed in adult thyroid. Here, we show that NKX 2.5 estimulated DUOX 2 promoter activity induced by TTF-1 and PAX 8 in HEK, suggesting that the re-expression of this factor might be able to activate Duox 2 promoter acitivity.

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Influência da pluviometria e sazonalidade nos níveis de TSH na triagem neonatal de estado da região amazônica – Brasil

Fernandes-Caldato MC, El Husny AS, Correa ARR, Ferreira AO, Silveira ECUnidade de Referência Materno-Infantil e do Adolescente, Laboratório de Pesquisa e Apoio Diagnóstico (LAPAD), Universidade do Estado do Pará, Belém, Brasil

A produção de TSH sofre variações circadianas já conhecidas. Variações anuais são descritas, entretanto há poucos estudos que as correlacionam com os fatores ambientais. A dosagem de TSH em papel filtro é prática, porém pode ser influenciada de forma diversa: pelo armazenamento das amostras, tempo de coleta e até pela variação sazonal e pluviométrica, indicando que a mudança ambiental pode alterar as propriedades do papel e influenciar a análise. objetivo: Investigar níveis de TSH na triagem para hipotireoidismo congênito em diferentes períodos do ano e entre diversas regiões do Pará, relacionando os achados com índices pluviométricos. Método: Foram estudados 261 indivíduos com resultados alterados no teste do pezinho de todo Pará em 1996-2004, distribuídos em períodos de maior ou menor índice de chuva acumulada. Avaliados aleatoriamente 50 indivíduos normais triados em agosto/2006 de cinco distintas regiões do Pará, conforme o valor de chuva acumulada de cada região. Resultados: Os níveis de TSH alterados no período de maior pluviometria foram em média 82,41 mUI/L e no período de menor pluviometria, 120,17 mUI/L (p < 0,05). Houve variação nos casos normais entre as regiões do estado: Sudoeste apresentou taxa média de 1.859, enquanto Nordeste apresentou 0,874; Sudeste, região metropolitana, Marajó e baixo Amazonas apresentaram 1.394, 1.616, 1.745 e 1.137, respectivamente (p = 0,003). Todavia, sem relações com a pluviometria. conclusões: A variação de TSH no período de maior chuva acumulada é evidente entre os casos alterados, mas não se confirmou em casos normais de diferentes regiões do estado. Impõem-se novos estudos que esclareçam a origem das variações detectadas.


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A case of congenital hipothyroidism with total iodine organification associated to monoallelic mutations

Mezalira PR1, Neves SC1, Dias V2, Viana M2, Chagas AJ2, Knobel M1, Medeiros-Neto G1, Rubio IGS1

1Thyroid Unit (LIM 25), University of Sao Paulo Medical School, Sao Paulo, Brazil; 2Nupad, Medice School of the University of Minas Gerais, Belo Horizonte, Brasil

introduction: Defects in the thyroid hormone synthesis are present in 20% children with congenital hypothyroidism (CH). Defects in the thyroid peroxidase (TPO) are the most frequent alterations. objective: To identify mutations in patient with congenital hipothyroidism with total iodine organification. Material e methods: We present a patient with severe CH, with total defect of iodine incorporation, who harbored two mutation in the TPO gene, Arg584Gln (new) and Arg665Trp. None of the mutations were identified in 100 controls. Other mutations were not found in the promoter, the 17 exons or in exon/intron borders of the TPO gene. Transmission of TPO alterations are recessive. Nevertheless, the father didn’t carry any of the mutations while the mother harbored both mutations. conclusion: These results indicated that both alterations are localized in the same chromosome. Analysis of the polymorphisms excluded mechanisms like uniparental disomy or isodisomy. The presence of monoallelic expression in the thyroid tissue may be the most consistent genetic event to explain the hormone deficiency of the patient. This mechanism was already detected in other studies and is supported by researches that indicate that monoallelic expression is a frequent event in autossomals.

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Resposta cardiopulmonar de pico e pós-esforço submáximo de pacientes com hipertireoidismo subclínico exógeno

Vigário PS1-2, Mendes ALM1, Chachamovitz DSO2, Teixeira PFS2, Oliveira FP1, Vaisman M2

1Labofise, Escola de Educação Física e Desportos, Universidade Federal do Rio de Janeiro; 2Serviço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

O hipertireoidismo subclínico (HpSC) está associado a manifestações no sistema cardiopulmonar. objetivo: Avaliar a resposta cardiopulmonar de pico e pós-esforço submáximo de pacientes com HpSC exógeno. Métodos: Estudo seccional; 19 pacientes com HpSC exógeno – tireoidectomia total ou parcial para carcinoma diferenciado de tireoide; TSH < 0,4 µUl/ml; T4L: 0.8 a 1.9 ng/dL (Pc; 47,9 ± 13,3 anos) e 23 controles (CT; 41,7 ± 0,2 anos). capacidade cardiopulmonar: teste ergoespirométrico. Variáveis: consumo de O2 (VO2, ml.kg.min-1); ventilação pulmonar (VE; l.min-1); pressão arterial (PAS e PAD; mmHg) e frequência cardíaca (FC; bpm), em três momentos (pico do esforço, 1° e 3° minutos de recuperação). Estatística: Mann-Whitney. Resultados: No pico do esforço, os pacientes apresentaram menores VE (Pc = 39,9 ± 11,3; CT = 53,6 ± 14,0; p < 0,05), VO2 (Pc = 21,1 ± 3,2; CT = 29,7 ± 6,2; p < 0,05) e FC (Pc = 158,8 ± 17,8; CT = 171,4 ± 14,1; p = 0,01), associada a menores carga de trabalho e tempo de esforço. A PAS (Pc = 182,6 ± 22,1; CT = 177,1 ± 26,1; p = 0,50) e PAD (Pc = 93,7 ± 9,0; CT = 89,0 ± 11,7; p = 0,10) foram menores entre controles, porém sem significância estatística. A recuperação da FC e do VO2 foi mais eficiente entre controles. A recuperação da PAS e VE foi menos eficiente entre os pacientes somente no 3° minuto. Os grupos não se diferiram quanto à recuperação da PAD. conclusão: O HpSC exógeno está associado à deterioração do sistema cardiopulmonar no pico e na recuperação pós-esforço submáximo.

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Hypothyroidism causes width’s reduction in testicular germinative epithelium

Romano RM, Salgado RM, Nunes MTDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

Background: Recent studies have shown that hipothyroidism affect male fertility, and thyroid hormone may be directly involved in this process. The spermatogenesis occurs in the seminiferous tubules, where spermatogonia are differentiated to sperm in the wall of the tubular epithelium. objective: To evaluate the histological characteristics of the testes of rats subjected to hypothyroidism using the analysis of linear morphometry of the seminiferous tubules. Methods: Samples of testes from control (C) or hypothyroids rats (TX) were fixed in Bouins solution and embedded in paraffin, for the preparation of histological sections stained with hematoxylin and eosin. All samples showed seminiferous tubules in the process of spermatogenesis in various stages of this cycle. Morphometry was performed in random fields selected in 100X magnitude. The images were captured and analyzed with the software advices tpsDig2 version 2.10. The groups were compared by one-way ANOVA test using the software Statistica 6.0. Results: There was a significant alteration in morphometric characteristics studied, as pointed by the epithelial width, which was 128.2 ± 3.3 µm in C and 97.5 ± 5.5 µm in TX (p 0.05). conclusions: Thyroid hormone deficiency causes impairment of spermatogenesis, reflected by lower width of the germinative epithelium. Romano, RM is recipient of Fapesp scholarship.


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Hipertiroidismo y embarazo: crisis tirotóxica materna e hipotiroidismo congenito central con hipertiroidismo neonatal transitorio

Gutierrez S, Calabrese MC, Abalovich M, Alcaraz G, Otero J, Stivel MGrupo de Trabajo Tiroides y Sector Pediatría” División Endocrinología l Hospital General de Agudos C. Durand Buenos Aires, Argentina

Paciente de 31 años que ingresó a UTI cursando embarazo de 21 semanas, con bocio, oftalmopatía, neumopatia, hipertermia (38.5ºC), hipertensión arterial (160/40 mmHg), excitación, taquicardia (160 x min), vómitos, insuficiencia cardíaca, edema de miembros inferiores. Había recibido irregularmente metimazol hasta 6 semanas antes. al ingreso: T4L: 7.7 ng/dl, T3: 587 ng/dl, TSH: < 0.01mUI/l, TRAb:86%. Se diagnosticó crisis tirotóxica (score de Burch y Wartofsky: 95). tratamiento: metildopa, antibióticos, furosemida metimazol 100 mg/d, hidrocortisona 300 mg/d en dosis decrecientes, propanolol endovenoso y luego 60 mg/d oral. Al 9º día: TSH: 0.05 mUI/l, T4L: 3.35 ng/dl, T3:265 ng/dl. Solicita alta voluntaria. Cumple irregularmente tratamiento ambulatorio presentando TSH suprimidas, TRAb entre 74 y 63%y T4L entre 3,5 y 1,45 ng/dl. Al parto, de 38 semanas, eutócico: T4L:1.76 ng/dl. La recién nacida pesó 2190 g (RCIU) APGAR 9-10. Presentó sucesivamente: Hipotiroidismo Congénito Central (HCC) confirmado a las 45 hs (TSH:0.63 mUI/l, T4:6.38 mcg/dl, T4L:0.84 ng/dl, T3: 54 ng/dl) al 5º día Hipertiroidismo Neonatal (HN) (TSH: 0.02 mUI/l, T4L: 4.18 ng/dl, T3: 337 ng/dl, TRAb: 54%); que requirió MMI 1 mg/kg/d en dosis decrecientes durante 43 días y nuevamente HCC luego de 15 días sin tratamiento (TSH:1.14 mUI/L, T4: 6.57 mcg/dl, T4L:0.97 ng/dl, T3: 130 ng/dl, TRAb: 13%). Inicia tratamiento con LT4. comentario: La crisis tirotóxica excepcionalmente complica el embarazo, además, el insuficiente tratamiento materno provocó en el hijo un HCC, al que se sumó HN Transitorio por pasaje de TRAb maternos. El caso evidencia las graves complicaciones materno-fetales de un hipertiroidismo materno insuficientemente tratado.

Thyroid auToimmune diseases & geneTiCs

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A meta-analysis of patients with chronic hepatitis C virus treated with interferon-alpha to determine the risk of induced thyroid autoimmunity

Andrade LJO, Bittencourt AV, Atta AM, Parana RCourse in Medicine of Federal University of Bahia; Salvador, Brazil

A relationship between hepatitis C virus (HCV) infection treatment with IFN-α and thyroid autoimmunity (TA) has been asserted on the grounds of epidemiological. In order to analysis the effect on TA of current anti-HCV treatment in HCV-infected patients, we performed a systematic review with meta-analysis of the available literature. The present meta-analysis was conducted to evaluate the strength and the consistency of the association between treatments with IFN-α for HCV infection and TA. A search of Medline, PubMed, and EMBASE was conducted with a systematic review of language of publication in English and other languages studies clinical. We identified 35 clinical trials with a total of 6.403 patients. Only studies in HCV subjects compared to control group with hepatitis B (AgHbs +) were considered. Five trials were selected for analysis involving a total of 625 patients with hepatitis C treatment with interferon-alpha and 456 controls with AgHbs + The relative risk of TA was regarded as the most reliable outcome end-point. The pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated from the raw study data using the Mantel-Haenszel methods. We used a statistical evaluation of heterogeneity by the c2-test to assess whether the variation in treatment effect within trials of the same group was greater than might be expected. The summary estimate for adjusted relative risk 3,41 (IC of 2,23 to 5,25), low-bias indicator of OR in the population = 3,30. Chi-square (1 DF) 37,891 (p = 0,000). Continuity correted chi-square (Yates) 36,831 (p = 0,000). Our meta-analysis indicates that treatment with IFN-α for HCV infection have an increased risk of TA.

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Thyroiditis in patients with hepatitis c infection treated with interferon alpha – revisional study

Andrade LJO, Bittencourt,AV, França LS, Atta AM, Parana RMedical Post-Graduate Program, UFBA, Salvador, Brazil

Background: Autoimmune thyroid disorders (DAT) has been described among the side-effects during interferon-alpha (IFN-α) therapy for chronic hepatitis C. Data suggest that the IFN-α precipitates thyroiditis by immune modulatory mechanisms and direct thyroid toxic effects. objective: To evaluate the prevalence of association between IFN-α therapeutic in patients (pt) infected with hepatitis C virus (HCV) and DAT in the main published studies in medical international literature. Material and methods: The research was carried out in PubMed – MedLine, using the key words: interferon-alpha, autoimmune thyroid and hepatitis C. It was selected the studies that evaluated the prevalence of DAT in pt with HCV in treatment with IFN-α. Results: It was found 9 studies regarding the prevalence of DAT in patients with HCV treated with IFN-α for 6-12 months and their prevalence ranged from 1,9% to 40%. conclusion: It’s important to evaluate the thyroid antibodies while on IFN-α therapy in pt with HCV, due to the association between DAT and interferon therapy.


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Tireoidite autoimune crônica em lactente com síndrome de Down

Dias EO, Martin RM, Miranda D, Tomimori EK, Knobel M, Camargo RAUnidade de Tireoide, FMUSP; São Paulo, Brasil

introdução: O hipotireoidismo em neonatos e lactentes geralmente é de etiologia congênita. A tireoidite de Hashimoto (TH) é rara em crianças com menos de 3 anos. Sabe-se que crianças com síndrome de Down (SD) têm alto risco de apresentar disfunção tireoidiana, incluindo TH e o hipotireoidismo congênito, sendo esse último 28 vezes mais frequente nessa síndrome. Relato de caso: Descrevemos caso de uma criança JPMS, masculino, 6 meses, parto cesáreo, gestação sem intercorrências, peso: 2.590 g, comp: 45 cm, com SD e TH, que havia apresentado teste do pezinho normal. Foram diagnosticados SD e cardiopatia congênita (CIV) ao nascimento. Pais não tinham história de doença tireoidiana. Solicitado TSH e T4L devido CIV descompensado com 3 meses, apresentando 2 dosagens de TSH elevados e T4L normais, sendo iniciado levotiroxina (LT4) 25 mcg/dia com 4 meses de vida. exames: TSH: 13.2 µU/ml, T4L: 1.17 ng/dl, TSH: 18.5 µU/ml, T4L: 1.0 ng/dl, anti-TPO: 45U/ml (VR < 35), anti-Tg: 107 U/ml (VR < 35), Tg: 1.6 ng/ml. usg tireoide: glândula de contornos levemente irregulares, textura heterogênea e parênquima moderadamente hipoecóico, compatível com doença autoimune. Discussão: Pacientes com SD têm aumento da prevalência de desordens autoimunes afetando órgãos endócrinos e não-endócrinos. A incidência de TH em lactentes com SD não é conhecida, tendo menos de 12 casos descritos na literatura. O presente caso nos alerta para o fato de que nem todos os casos de hipotireoidismo em lactentes é devido ao hipotireoidismo congênito. conclusão: TH em portadores de SD, apesar de ser rara nessa faixa etária, deve ser identificada e tratada precocemente para evitar sequelas neurológicas permanentes. Referências: Tuysuz B, Beker BD. Thyroid dysfunction in children with Down’s syndrome. Acta Paediatr. 2001;90 (12):1389-93; Shalitin S, Philip M. Autoimmune thyroiditis in infants with Down’s syndrome. J Pediat Endocrinol Metab. 2002; 15 (5):649-52.

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Prevalence of thyroid auto-immunity in patients with prolactinoma

Saldanha F1, Violante AHD2, Freitas MMW1, Loureiro C1, Ballarini M1, Lamounier Filho A1, Naliato ER1, Vaisman M2

1Endocrine Unit, Medical School; 2Hospital Universitário Clementino Fraga Filho; Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brazil

Background: Prolactin is a hormone that possesses immunomodulatory properties. objectives: The aim of this study was to evaluate the prevalence of thyroid autoimmunity in patients with prolactinoma. Methods: Seventy seven patients with prolactinoma and 56, sex- and age- matched healthy, subjects were evaluated. Serum levels of PRL, free thyroxine, thyroid-stimulating hormone and peroxidase antibody (TPOAb) were measured in all patients and controls. Results: There was no significant difference between the frequencies of positive TPOAb in patients and normal subjects (13,0% x 8,9%, p = 0,58). Even if the patients were divided in relation to tumor size at diagnosis, no differences were found. However, when the patients were divided by the current levels of prolactin, the frequency of the TPOAb in the hyperprolactinemic group was 18.8% x 3.4% in the group without hyperprolactinemia. This difference tended to be significant (p = 0.07). conclusion: We did not observe a greater prevalence of thyroid autoimmunity in patients with prolactinoma treated.

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Avaliação da presença de anticorpos antitireoperoxidase e disfunção tireoidiana na síndrome de Down

Barros CJV, Monteiro SHV, Imbroise R, Ribeiro MG, Beserra ICR, Guimarães MMServiços de Endocrinologia do IPPMG e do HUCFF, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

objetivos: Avaliar a presença de anticorpos antitireoperoxidase e a ocorrência de disfunção tireoidiana na síndrome de Down. Metodologia: Foram avaliados prontuários de pacientes com síndrome de Down estabelecida pelo Serviço de Genética. Foram anotados sexo, idade, função tireoidiana e dosagem de anticorpos antitireoperoxidase. Os dados foram agrupados por sexo, disfunção tireoidiana, positividade de anticorpos e analisados pelo programa Epi-Info versão 3.2, sendo significante um p valor < 0,05. Resultados: Em 44 prontuários (24 femininos e 20 masculinos), com idades de 4,1 e 18,4 anos (média de 11.6 ± 4), havia a dosagem de anticorpos. Disfunção tireoidiana foi encontrada em 33 (75%) e 11 (25%) eram eutireoidianos. A prevalência de disfunção foi semelhante nos dois sexos (p = 0,36). Os anticorpos encontravam-se positivos em 11 (25%), sendo que 10 (90,1%) destes tinham disfunção tireoidiana e em 1 a função tireoidiana era normal, com relação de ODDS de 4.43. Na disfunção tireoidiana a positividade de anticorpos foi presente em 8 (72,7%) pacientes com hipotireoidismo sub clínico, 1 (11,1%) com hipotireoidismo clínico, outro com hipertireoidismo e outro com doença nodular e eutireoidismo. Quando considerada a positividade de anticorpos, estes estavam presentes em 10 (90,9%) pacientes femininas e em 1 (9,1%) masculino, com diferença significativa entre os dois sexos (p = 0,005). conclusão: A positividade de anticorpos antitireoperoxidase é mais prevalente no sexo feminino, apesar de a disfunção tireoidiana ocorrer igualmente em ambos os sexos.


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Interaction of type 2 iodothyronine deiodinase THR92ALA and peroxissome proliferactor-activated receptor gama-2 Pro12Ala polymorphisms in the modulation of insulin resistance

Estivalet AAF, Leiria LB, Canani LH, Maia AL, Crispim DEndocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Thyroid hormones play an important role in insulin action by up-regulating the glucose transporter 4 (GLUT4) expression in skeletal muscle. The iodothyronine deiodinase type 2 (D2) enzyme converts the inactive thyroid hormone T4 in the active form T3. The Ala/Ala genotype of the Thr92Ala polymorphism in the D2 gene is associated with a decreased D2 activity and seems to be associated with insulin resistance (IR). The peroxissome proliferactor-activated receptor gama-2 (PPAR-gama2) gene encodes a transcription factor involved in insulin signaling, and the Pro12Ala polymorphisms has been inconsistently associated with IR. A recent study reported an interaction between these polymorphisms in the modulation of metabolic syndrome. Thus, the aim of this study was to investigate the combined effect of D2-Thr92Ala and PPAR-gama2-Pro12Ala polymorphisms on IR in patients with type 2 diabetes. We analyzed 580 type 2 diabetic patients, and IR was inferred using the HOMA-IR index. The allelic frequencies of the D2-Thr92Ala and PPAR-gama2-Pro12Ala polymorphisms were 0.408 and 0.073, respectively, and their genotypic frequencies were in Hardy-Weinberg equilibrium. The HOMA-IR index was similar among patients with the PPAR-gama2-Pro12Pro genotype, irrespectively of the D2 genotypes (P = 0.310). However, patients with the PPAR-gama2- X12Ala (Pro/Ala or Ala/Ala) and D2-Ala92Ala genotypes presented HOMA-IR index, more elevated (mean [range] = 11.4[2.6-28.2]) than patients with the PPAR-gama2-X12Ala and D2-Thr92Ala or Thr92Thr genotypes (2.5[0.5-15.1] and 4.4[1.3-11.3], respectively; p = 0.013). conclusion: in our population the D2-Thr92Ala and PPAR-gama2-Pro12Ala polymorphisms might interact in modulation of IR, and this interaction could be an interesting therapeutic target.

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Is there a different risk profile for Graves’ disease in children and adults?

Cury AN, Bufalo NE, Longui CA, Scalissi NM, Monte O, Ward LS1Molecular Genetics of Cancer Laboratory, Department of Internal Medicine, Medical Science School (FCM), State University of Campinas (Unicamp), Sao Paulo, Brazil; 2Pediatric Endocrinology Uni, Santa Casa de Sao Paulo, Sao Paulo, Brazil

The susceptibility to autoimmune thyroid diseases (ATD) involves a complex interaction of environmental and genetic factors. Cytotoxic T lymphocyte antigen-4 (CTLA-4) loci, in chromosome 2q33, has been largely studied in several populations, and is currently considered to be one of the main non-HLA genes associated with Graves’disease (GD) susceptibility. Also, we previously demonstrated that Glutathione S-Transferase (GST) family of detoxification genes modify the risk to GD. Our aim was to study the influence of + 49A > G and -318C/T polymorphisms of the CTLA-4 gene in Brazilian children and adults GD patients and their relationship to GSTT1, GSTM1, GSTP1 polymorphic inheritance. Using PCR-RFLP analysis, we genotyped 46 GD patients who were less than 18 years old by the time of GD diagnosis (35 girls and 11 boys, 12.17 ± 4.19 years old) and 71 GD adult patients (41 women and 30 men, 35.21 ± 12.17 years old) carefully matched to a stringent control group of 577 individuals for the interest genes. CTLA4-318, CTLA4A49G, GSTT1, GSTM1 and GSTP1 had a similar distribution in children and adults and did not differ from the control population. However, GSTP1 combined to CTLA-4 A49G variants were more frequent among GD adults (38.4%) than among children (35.2%) (X2 = 4.175; p = 0.0410). We did not find any association between the genes investigated and any clinical characteristic of GD, either among children nor in adults. The fact that children exhibit a different genetic profile of risk suggests that diverse age-related environmental triggers are involved in GD.

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Autoimunidade tireoidiana e abortamento espontâneo

da Cunha AB, Meira DM, de Brito KRS, Thomaz LPM, da Cruz RPDepartamento de Endocrinologia do Hospital Universitário Professor Edgard Santos (HUPES); Salvador, Brasil

introdução: Abortamento espontâneo é uma das complicações mais comuns da gestação, com 30% a 50% dos casos sem etiologia conhecida. Como causas, destacam-se fatores genéticos, anatômicos, hormonais, infecciosos e ambientais. O fator autoimune seria outro responsável. Em mulheres com história de abortamento, a presença de anticorpos como o anti-TPO e antitireoglobulina parece ser fator de risco independente, mesmo quando as essas encontram-se clínica e bioquimicamente eutireoidianas. caso clínico: Paciente feminina, 24 anos, com relato de dois abortamentos espontâneos prévios – um no segundo e outro no primeiro trimestre. Paciente hígida, sem história pessoal e familiar de comorbidades, com exame físico normal. Cariótipo do casal, anticoagulante lúpico e anticardiolipina, sem alterações. Prolactina, FSH, LH, estradiol e progesterona normais. VDRL e sorologias virais negativos. TSH: 1,72 µUi/mL (VR: 0,27 a 5,2), T4 livre: 1,21 ng/dL (VR: 0,81 a 1,7) e anti-TPO: 487 (VR: até 12). Introduzida levotiroxina 25 µg/dia. Após quatro meses, teve nova gestação, sem intercorrências, com parto a termo e RN saudável. Não descontinuou a medicação. Discussão: O risco de abortamento espontâneo em mulheres com hipotireoidismo subclínico ou anticorpos tireoidianos parece ser mais elevado. Altos títulos destes levariam a uma função subnormal da tireoide, sem expressão clínica ou laboratorial, mas comprometendo a função reprodutiva. Outra hipótese é que seriam marcadores de disfunção de células T. Questiona-se o tratamento com levotiroxina ou imunoglobulina, devido à ausência de consenso sobre o assunto.


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Síndrome de anticuerpos antifosfolipido, enfermedad de Graves Basedow y carcinoma papilar de tiroides

Falcon-de-Legal E1, Almiron R1, Bogado L2

1Servicio de Endocrinología y Metabología; 2Servicio de Cirugía de Cabeza y Cuello; Hospital Central, Instituto de Previsión Social; Asunción, Paraguay

Background: Se han reportado algunos casos de enfermedad de Graves Basedow y carcinoma papilar de tiroides; pero la aparición concomitante de las dos enfermedades anteriores junto con el síndrome de anticuerpo antifosfolípido es muy rara. Reporte de caso: MKG, F, 46 años. Se presentó con síntomas de hipertiroidismo, exoftalmia, bocio, en tratamiento con propil tiuracilo 150 mg al día y propanolol 80 mg al día durante más o menos 4 meses de evolución, sin mejoría del cuadro. Portadora de un bocio de larga data con aumento de tamaño en los últimos meses. Alegaba quejas de abortos de repetición. Fueron realizados exámenes de prueba de función tiroidea, que demostraron TSH 0,00 uUI/ml, T3 4,94 ng/ml y T4 > 24 ug/dl. La ecografía de tiroides mostró la glándula hipervascularizada con diagnóstico de tormenta tiroidea. Fue tratada con altas dosis de propil tiuracilo, propranolol y prednisona. Fueron solicitados exámenes de anticuerpos anticardiolipina IgG y anticuerpos anticardiolipna igM que demostraron positivo. Después de compensada del cuadro de tirotoxicosis, fue sometida a tiroidectomía total. Se confirmó por anatomía patológica Enfermedad de Graves Basedow y un hallazgo de carcinoma papilar convencional de tiroides. conclusión: El caso descrito muestra que pueden aparecer pacientes con estas patologías y que es de fundamental importancia investigar el síndrome de anticuerpo antifosfolípido ante un paciente con esta sospecha. El hallazgo de un carcinoma papilar nada más aporta, en el sentido de que no es raro encontrarlo con la enfermedad de Graves.

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Evaluation of thyroid patients infected by hepatitis C virus: correlation with polymorphisms of CTLA-4 gene

Lima EU1, Barros RK3, Knobel M2, Mendes-Correa MC3, Zambrini H3, Marui S1

1Laboratory of Cellular and Molecular Endocrinology Unit of Thyroid-LIM-25; 2Endocrine Division; 3Division of infectious diseases, Hospital das Clinicas, Faculty of Medicine of the University of Sao Paulo; Sao Paulo, Brazil

Background: Infection due to hepatitis C (HCV) is related to autoimmune thyroid disease (AITD) not only because of interferon-α treatment, but also due to association with thyroid autoimmunity. The mechanism involved in triggering autoimmunity by virus C is not yet clarified. Genetics factors are probably required for development of AITD in patients with HCV. CTLA-4 gene is involved in the maintenance of immune tolerance and its polymorphisms are known associated with Graves disease. objectives: To characterize the manifestations of thyroid disease in patients chronically infected with HCV and correlate to polymorphisms -318C > T, A49G and CT60 CTLA-4 gene frequencies. Methods: We studied infected patients with HCV (group 1, n = 99), patients with Graves disease (group 2, n = 38), and individuals without AITD (group 3, n = 190). All polymorphisms were analyzed by PCR-RFLP. Thyroid function and autoantibodies were measured by IFMA, and thyroid ultrasound (US) were performed in group 1. Results: In group 1, we identified 5% with thyroid dysfunction and 4% with AITD. At US, 23% presented nodules, 40% ≥ 1 cm, 52% ≥ 2 nodules and most mixed solid and cystic lesions. Parenchyma was heterogeneous in 68% and with increased vascularization in 40%. We did not observe a higher frequency of pathological genotypes in groups 1 and 2 compared to group 3. conclusion: We found no increased prevalence of thyroid dysfunction or AITD, as well as genetic factors predisposing autoimmunity in our HCV cohort. The main risk marker for AITD in patients with HCV remains unknown.

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Maior chance de angioedema em pacientes com urticária crônica idiopática e doenças da tireoide

Missaka RFBG, Penatti HC, Silvares MRC, Nogueira CR, Mazeto GMFSDepartamentos de Clínica Médica e Dermatologia, Faculdade de Medicina de Botucatu, Unesp, Botucatu, Brasil

introdução: A urticária crônica idiopática (UCI) pode apresentar-se com angioedema, quadro mais grave, o qual acomete profundamente derme e mucosas. A associação entre UCI e doenças da glândula tireoidea (DT) tem sido relatada. objetivos: Avaliar se pacientes com UCI e DT apresentam maior chance de angioedema do que os sem DT. Métodos: Foram avaliados os prontuários de 115 pacientes com UCI, acompanhados no Ambulatório de Alergia da Faculdade de Medicina de Botucatu: 91 mulheres (79,13%) e 24 homens, com idade média de 38,14 anos. Estes foram submetidos a exame clínico e dosagens de tireotrofina, tiroxina livre e anticorpos antitireoide, e classificados como portadores ou não de tireopatia, doença autoimune tireoidea (DAT; tireoidite de Hashimoto-TH) e/ou disfunção (hiper ou hipotireoidismo). Foram estudados a frequência de DT e de angioedema, bem como a chance pacientes acometidos pelas primeiras apresentarem o segundo. Resultados: Tireopatias foram diagnosticadas em 43 pacientes (37,39%), os quais apresentaram 54 DT: 28 disfunções (24,35%), 22 DAT (19,13%; 17 TH) e quatro doenças nodulares. Angioedema ocorreu em 70 pacientes (60,87%). Os pacientes com hipotireoidismo, disfunção, tireopatia, TH e DAT apresentaram, respectivamente, 4,6; 4,7; 7,5; 10,85 e 16 vezes mais chance de experimentar angioedema do que os sem DT. conclusão: No presente estudo, observou-se que os pacientes com DT apresentaram maior chance de angioedema. agradecimentos: Os autores agradecem ao consultor Hélio Rubens de Carvalho Nunes, do Grupo de Apoio à Pesquisa da FMB – Unesp, pela análise estatística e à Fapesp, pelo auxílio financeiro (processos no. 07/54859-1,07/54860-0).


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Role of parity and estrogens in the risk of autoimmune thyroid disease in a population-based study of Japanese-Brazilians

Sgarbi JA1-2, Matsumura L1, Kasamatsu T1, Maciel RMB1

1Laboratory of Molecular Endocrinology, Division of Endocrinology, Federal University of Sao Paulo, Sao Paulo, Brazil; 2Division of Endocrinology, Department of Medicine, Faculdade de Medicina de Marilia, Marília, Brazil

Background: It has been suggested that the female thyroid autoimmunity preponderance may be due to the effect of estrogens on the immune system or by the transplacental passage of fetal cells into maternal tissues (microchimerism). To confirm this hypothesis, parity should be a risk factor for thyroid autoimmunity. objective: To investigate the influence of previous parities, abortions and the use of estrogens on the risk of thyroid autoimmunity. Methods: We examined all women (n = 675) from a Japanese-Brazilian population aged above 30 yr. Thyroid peroxidase (TPOAb) and thyroglobulin antibodies (TgAb), TSH and FT4 were measured by immunofluorimetric assays. Urinary iodine concentration (UIC) was measured by a colorimetric semi-automated method. Data were analyzed in logistical regression models to obtain the odds ratio (OR) and 95% CIs. Results: Positive TPOAbs and TgAbs were present in 11.3% and 13.6% of women, respectively. After adjustment for age, the risk of having positive TPOAb [OR, 1.21 (95% CI, 0.7 – 1.9)] or TgAb [OR, 1.0 (95% CI, 0.6 – 1.6)] among women who had one or more parity was not different from those who had never given birth. There was no association between previous abortions or the use of estrogens with thyroid autoimmunity. In addition, mean serum TSH and FT4 levels were similar between groups, but median UIC was higher in women with previous parity compared to those with no previous one. conclusions: These data do not support a role of microchimerism or of estrogens for the female thyroid autoimmunity preponderance.

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Thyroid cells up-regulate toll-like receptor 4 expression and pro-inflammatory mediators in response to LPS stimulation: new players in the innate immune response?

Nicola JP, Gatti G, Maccioni M, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología. CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

Environmental factors such as bacterial toxins have been proposed to be involved in pathological processes of the thyroid gland. Despite intensive research, little is known about the immunobiology of the thyroid cell and its relation to thyroid diseases. Microarray analysis demonstrated the whole set of toll-like receptors (TLRs) expression in the thyroid cell, suggesting that these cells could recognize a broad spectrum of microbial molecular patterns. The main goal of this work was to investigate how thyroid cells respond to LPS as an inflammatory stimulus. As we previously demonstrated, thyroid cells constitutively express TLR4, MD2 and CD14 at the plasma membrane. TLR4 and MD2 expression, but not CD14 expression, were up-regulated in response to LPS at both mRNA and protein levels measured by RT-PCR and Western Blot. Flow citometry experiments yielded similar results about increased TLR4 and MD2 expression at the plasma membrane. We then investigated whether thyroid cells could respond to LPS regulating the expression of different pro-inflammatory genes. RT-PCR analysis was performed to measure chemokine mRNA levels. LPS treatment increased the expression of the chemokines CXCL8, CXCL10, CCL2 and CCL5. Taken together these results major indicate that thyroid cells can respond to the LPS-inflammatory stimulus by increasing the expression of its receptor complex and inducing or up-regulating the expression of several chemokine genes. Our results suggest that the thyroid cell is capable of mounting a response to LPS, raising the question whether these cells could turn into active players of the innate immunity, able to initiate an inflammatory process.

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A novel mutation in selenocystein binding protein type 2 gene is associated with abnormal thyroid hormone metabolism: case report

Leiria LB, Meyer ELS, Dora JM, Maia ALThyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

Background: The selenoproteins are enzymes that present a selenocysteine (SEC) in its catalytic center, and compound important cellular roles, such as thyroid hormone metabolism, cellular oxidation, glucose metabolism and sperm maturation. The type 2 iodothyronine deiodinase (D2) is a selenoprotein that catalyze the removal of iodine from the outer ring of thyroid hormone T4 activating in T3. Disruption in mouse D2 gene (Dio2) was associated with alterations in T4/T3 regulation and elevated TSH levels. Recently it was reported that patients with mutations in seleocystein binding protein type 2 (SBP2), a required in the mechanism of the insertion of SEC in selenoproteins, presents a laboratorial characteristic similar to that described in D2 disrupted animals. Methods: We performed a case study of a 13-year old boy with a diagnossis of congenital hypothyroidism due to thyroid agenesis, followed at the Endocrine Outpatient Clinic of our institution. The patient presented mental retardation, high levels of TSH, low levels of T4 and T3, and bone delayed development. Interesting, to normalize TSH levels was administrated doses of T4 (4.4 mcg/kg) or association with T3. His mother had normal levels of these hormones. DNA sequencing of Dio2 and SBP2 genes were performed. Results: No mutation in Dio2 coding sequence was observed, however, we found a heterozygous mutation in exon 10 from SBP2 gene, a change to asparagines to lysine (AAT to AAG) at codon position 439. conclusions: Additional analyzes will be necessary to determine the role of this mutation in patient phenotype.


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Selenio y autoinmunidad tiroidea

Calabrese MC, Abalovich M, Gutierrez S, Elias NGrupo de trabajo “Tiroides” de la División Endocrinología del Hospital General de Agudos C. Durand Buenos Aires, Argentina

introducción: El selenio (Se) modifica la expresión de al menos 30 selenoproteínas, como la familia de la glutatión peroxidasas, tioredoxin reductasa y deiodinasas, que actúan como antioxidantes y en el metabolismo de hormonas tiroideas. objetivos: Averiguar si, como se ha postulado, el Se es capaz de descender los niveles de anticuerpos antiperoxidasa (aTPO) en pacientes con autoinmunidad tiroidea (AIT). Pacientes y métodos: Se evaluaron 24 mujeres eutiroideas de 25 a 72 años (X 48), con aTPO positivo (19 bajo LT4). Fueron tratadas con 200 mcg/día de Se contenidos en un preparado antioxidante. Se midieron TSH y aTPO antes y post 3 meses de tratamiento. aTPO fue medido por Quimiolumniscencia ( < 35 UI/ml), MEIA ( < 0,5 UI/ml). Los aTPO se expresan como número de veces respecto del límite superior normal, teniendo en cuenta el doble del coeficiente de variación para considerar cambios pre y post tratamiento. Resultados: aTPO pre Se X 10.23 veces (1.56-152) vs. 10 (1.27-76) post Se p: ns (0,44). Sin cambios: 6/24 pacientes. Incrementaron: 10/24 (entre 16 y 105%). Descendieron: 8/24 (entre 18 y 89%). TSH: pre Se X 1.32 (0.11-2.8) vs. post Se 1.5 (0.06-3.62) p: ns (0.34). conclusiones: En este estudio preliminar no observamos efecto benéfico del Se sobre los niveles de aTPO. Lo heterogéneo de las respuestas permitiría hipotetizar que ciertos pacientes podrían ser deficitarios en Se y responder al tratamiento mientras que los no respondientes no lo sean. La determinación de Se sérico podría esclarecer este interrogante

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Mixedema pretibial grave

Munizaga F1-2, Hidalgo1 C, Munizaga3

1Unidad de Endocrinología Hospital San Borja-Arriarán; 2Universidad de Chile; Campus Central; 3Universidad Católica del Norte; Santiago, Chile

introduccion: El mixedema pretibial es una complicación infrecuente en la enfermedad de Graves, el diagnóstico es clínico, el tratamiento no es claro y los resultados no son adecuados. Presentamos un caso severo y una nueva alternativa terapeútica, basándonos en los buenos informes de algunos reportes de uso de bolos de metilprednisolona en casos de orbitopatía y asumiendo una etiopatogenia autoinmune común. caso clinico: Hombre de 40 años, portador de bocio difuso hipertiroideo y exoftalmo leve sometido a tratamiento con radioyodo. Seis meses después, estando hipotiroideo y en tratamiento con levotiroxina 175 mcg al día, presenta agravación de compromiso ocular y aparición de lesiones dérmicas en región anterior de ambas extremidades inferiores. Esto es progresivo impidiendo colocarse zapatos y luego deambular. Se descartó problema vascular mediante eco doppler venoso. Al examen el paciente tenía exoftalmo bilateral de 27 y 26 mm, con discreta diploplia a derecha, sin signos congestivos. No tenía bocio y el examen segmentario de tórax y abdomen era normal. Las extremidades inferiores presentaban aumento de volumen bilateral que se manifestaba como lesiones dérmicas solevantadas de la región anterior de ambas piernas comprometiendo toda la zona infra-rotuliana y dorso de pie. Diámetro máximo en pierna derecha era de 44 cm y de 43 cm en pierna izquierda. exámenes de laboratorio: TSH 1.8 mUI/ml TRAB: 94.6%, (VN < 11%). Perfil bioquímico, lipídico, hemograma y VHS normales. Por compromiso ocular y dérmico se decide tratar con bolos de metilprednisola: 1 gr EV/día por 3 días, procedimiento que fue bien tolerado y sin complicaciones. Luego de seis meses de evolución se observa mejoría en la motilidad ocular y regresión parcial del exoftalmo (23 y 24 mm). Las lesiones dérmicas presentan una disminución importante, con reducción del diámetro de piernas, 39 cm. en pierna derecha y 38 cm en pierna izquierda, lo que se traduce en una deambulación normal y el paciente puede nuevamente usar calzado. Se reevalúan exámenes de laboratorio: TSH: 1.9 mUI/ml y TRAB: 40.3%. conclusion: La terapia con metilprednisola es una alternativa útil y sin complicaciones en el mixedema pretibial grave.

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Detecção da resistência ao hormônio tireoidiano pela triagem neonatal

Magalhães PKR, Maciel LMZDivisão de Endocrinologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto; Ribeirão Preto, Brasil

A síndrome da resistência ao hormônio tireoidiano (RTH) é uma doença hereditária, rara, causada principalmente por mutações no gene b do receptor do hormônio tireoideo (TRb). Usualmente, seu diagnóstico é realizado diante de concentrações elevadas dos hormônios tireoidianos associadas a valores de TSH não suprimidos em crianças que apresentam bócio, hiperatividade e/ou atrasos de crescimento ou desenvolvimento. Detectamos RTH ao nascimento pelo exame rotineiro de triagem neonatal. O caso índice nasceu de parto normal a termo, sem intercorrências, com peso de 2.920 g e comprimento de 45 cm. Apresentou icterícia após o nascimento com regressão espontânea, sem outras alterações. Frequência cardíaca de 140 bpmin. TSH neonatal foi de 13,1 µU/ml, TSH confirmatório no soro de 4,3 µU/ml, T4 total de 19 µg/dl, T4 livre de 3,7 ηg/dl e T3 livre de 6,7 pg/ml. O sequenciamento direto do TRb revelou a presença da mutação c.1357C > A (P453T). O estudo de sua família demonstrou a presença da RTH em sua irmã de 1 ano e 3 meses, em seu pai de 34 anos e em seu avô paterno de 75 anos. Todos apresentavam bócio e apenas seu pai havia tido o diagnóstico errôneo de hipertireoidismo, sendo tratado com drogas antitireoidianas. Este caso ilustra que a interpretação criteriosa das concentrações de T4 total em um recém-nascido reconvocado por TSH neonatal discretamente alterado poderá servir para o diagnóstico da RTH.


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THyROID HORMONE ACTION & METABOLISM

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Efeito do treinamento físico de natação sobre o ganho de massa corporal e função tireoidea de ratas ovariecto-mizadas

Ignacio DL, Fortunato RS, Frankenfeld TGP, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brasil

introdução: O exercício físico e os hormônios tireoideos (HTs) regulam o gasto energético, e a deficiência de estrogênio causa maior ganho de massa corporal. objetivo: Avaliamos a influência do treinamento físico sobre o ganho de massa corporal e função tireoidea de ratas ovariectomizadas. Resultados: As ratas ovariectomizadas sedentárias (OS) e treinadas (OT) tiveram um aumento significativo de massa corporal comparadas aos grupos controles (CS e CT). As concentrações totais séricas de T3, T4 e TSH não alteraram significativamente com o protocolo de exercício nem com a ovariectomia. A atividade D1 hipofisária aumenta nos animais treinados, mas a castração impede esse aumento. A atividade da D2 no TAM aumentou no grupo CT em relação aos grupos CS e OS. A atividade da D2 hipofisária diminui significativamente em ambos os grupos castrados em relação ao CS. conclusões: O treinamento físico foi capaz de impedir em parte o ganho de gordura corporal, sem alterações na ingestão alimentar. A função tireoidea está normal após 8 semanas de castração e as fêmeas castradas mantêm massa corporal aumentada, indicando que a diminuição da função tireoidea não estaria relacionada à maior massa corporal. O treinamento de ratas controle aumenta significativamente a atividade desiodase tipo 1 na hipófise e tipo 2 no tecido adiposo marrom, efeitos esses abolidos pela castração. Apoio financeiro: Pronex, CNPq, Faperj, Capes.

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Iodotironinas desiodases são reguladas pela administração crônica de 3,5-diiodotironina

Padrón AS, Pantaleão TU, Andrade BM, Araújo RL, Carvalho DPLaboratório de Fisiologia Endócrina, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

introdução: Recentemente, a 3,5-diiodotironina; 3,5-T2 tem sido relacionada ao controle do gasto energético em ratos hipotireoideos. objetivo: Investigar os efeitos do tratamento diário com 3,5-T2 (25, 50 e 75 µg/100 g p.c.), em ratos, durante o desenvolvimento da resistência insulínica e do sobrepeso. Metodologia: Ratos Wistar machos (dos 3 aos 6 meses de idade) receberam 3,5-T2 (25 µg, 50 µg e 75 µg/100 g de peso, s.c.), durante 90 dias. Resultados: O envelhecimento promoveu resistência insulínica nos ratos Wistar e o tratamento com 3,5-T2 normalizou a intolerância à glicose. O 3,5-T2 reduziu significativamente as concentrações plasmáticas de T3 e T4 de forma dose dependente. O TSH estava normal ou diminuído, apesar dos valores diminuídos de T3 e T4, sugerindo uma ação direta do 3,5-T2 sobre o mecanismo de regulação e de biossíntese dos hormônios tireoideos. Apesar dos níveis reduzidos dos hormônios tireoideos, o consumo de oxigênio nos grupos tratados com 3,5-T2 não diferiu do grupo controle e a atividade da D1 hepática estava aumentada, sugerindo uma modulação direta pelo T2. A D1 tireoidea reduziu significativamente. conclusão: O tratamento crônico com 3,5-T2 causa disfunção tireoidea. Demonstramos, pela primeira vez, que o 3,5-T2 modula positivamente a desiodase tipo 1 hepática e aparentemente diminui a resposta tireoidea ao TSH ou sua bioatividade. Apoio financeiro: CNPq, Faperj, Capes, Pronex.

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Efeito da restrição alimentar e da administração de triiodotironina (T3) sobre a morfometria cardíaca em ratos obesos

Marino J, Luvizotto RAM, Nascimento AF, De Sibio MT, Almeida NCP, Olimpio RMC, Nogueira CRLaboratório Experimental de Clínica Médica, Faculdade de Medicina Botucatu, Unesp; Botucatu, Brasil

introdução: Obesidade e doses suprafisiológicas de T3 provocam alterações na morfometria cardíaca. A restrição alimentar (RA) tem sido utilizada como estratégia para tratamento da obesidade. Por outro lado, durante a RA há diminuição dos hormônios tireoidianos (HT), assim a utilização desses hormônios durante esse período seria um tratamento promissor para a obesidade. objetivo: Analisar os efeitos da associação entre RA e administração de dose suprafisiológica de T3, por curto período, sobre a morfometria cardíaca de ratos obesos. Métodos: 24 ratos Wistar machos foram submetidos à dieta hipercalórica, por 20 semanas, para indução de obesidade. Após esse período, foram separados em Obeso (OB); animais com restrição alimentar de 25% (CR); animais obesos e administração de T3 (OBS); e animais com restrição e administração de T3 (CRS). Os animais CR e CRS foram submetidos à RA por 8 semanas e a dose suprafisiológica de T3, administrada por 2 semanas, foi de 25 mg/100 g de peso animal. A morfometria cardíaca foi analisada por meio de quantificação de colágeno intersticial (picrosirius red) e área seccional transversa dos cardiomiócitos (HE). Resultados: Não houve diferença significante na fração de colágeno intersticial entre os grupos. Contudo, a associação entre RA e administração de T3 diminuiu a área seccional transversa dos miócitos. conclusão: A associação entre RA e T3 reduz a área seccional transversa dos miócitos, um indicador que, em 2 semanas, o HT já tem ação na morfometria das células cardíacas.


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Bone and mineral metabolism in resistance to thyroid hormone

Dare GLR, Magalhães PKR, de Castro M, Maciel LMZDivision of Endocrinology, Department of Internal Medicine, School of Medicine of Ribeirão Preto; Ribeirão Preto, Brazil

Background: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome of reduced tissue responsiveness to thyroid hormone usually due to mutations in the thyroid hormone receptor b (TRb). Few studies have been conducted to investigate bone and mineral metabolism in RTH. objective: To evaluate calcium, phosphorus, magnesium and paratohormone (PTH) levels at baseline and at 3, 6 and 9 days after the oral administration of graded doses of T3 (50, 100, and 200 mg/day, each given over three days) in four unrelated individuals with RTH comparing with 22 normal controls. Methods: Phosphorus clearance and bone mineral densitometry were performed in basal conditions in all patients. The age at the RTH diagnosis varied from 14 months to 29 years. Three affected individuals were clinically euthyroid, except for presenting tachycardia and goiter and one patient had symptoms and signs of hyperthyroidism, immediately after birth. Direct sequencing analysis of the TRb gene revealed in these RTH individuals four previously reported mutations: c.949G > A, c.1313G > A, c.1357C > A and c.1358dupC. Results: All patients, evaluated at age of 15, 16.5, 27 and 36 years old showed basal phosphorus below the CI95% of normal controls (1.7-3.5 vs. 4.2 ± 0.6 mg/dl); low phosphorus clearance (4-7 ml/min). High PTH levels (58-91 pg/ml) were observed in RTH adult patients as compared to RTH adolescents and controls. Osteopenia/osteoporosis was observed in two out of four patients. There were no changes of total and ionic calcium, phosphorus, alkaline phosphatase, and PTH levels with L-T3 treatment. conclusions: We found reduced bone density and the occurrence of hypophosphatemia in the RTH. This latter finding has not been previously reported and it is probably due to a secondary hyperparathyroidism.

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Thyroid hormone transport in erythrocytes from patients with hyperthyroidism and hypothyroidism

Oliveira AS, Azevedo MF, Neves FAR, Simeoni LALaboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasilia; Brasilia, Brazil

Background: Most effects of thyroid hormones (THs) are mediated by binding of 3,5,3’-triiodo-L-thyronine (T3) to thyroid hormone receptors (TRs). To bind to TRs, T3 must enter the target cells. The mechanism that regulates THs transport across the cell membrane is not clear. objectives: The aim of this study is to characterize whether different THs levels can modulate the entry and exit of THs in red blood cells observed in patients with hypothyroidism and hyperthyroidism. Methods: We measured uptake (1, 5, 10, 30, 60, 120 and 180 min) and efflux (60 min) of [125I]-T3 and [125I]-T4 in erythrocytes in normal individuals (control) and hypothyroid and hyperthyroid patients. Statistical analysis was performed by ANOVA complemented with Newman-Keuls Statistical. Results: Uptake of [125I]-T3 and [125I]T4 in erythrocytes hyperthyroidism as well as the uptake of [125I]T4 in hypothyroidism showed no statistical difference in comparison to control. However, the uptake of [125I]-T3 in erythrocytes from hypothyroid patients showed a statistically significant increase when compared to the control at 60, 120 and 180 min. Moreover, [125I]T3 efflux was decreased in erythrocytes from hypothyroid patients. In contrast, [125I]T3 efflux in erythrocytes of hyperthyroid patients was 31% higher when compared with the control (p < 0.005). There was no difference in [125I]-T4 efflux from cells of hyperthyroid and hypothyroid. conclusions: THs levels modulate T3 and T4 transport across the plasma membrane. In excess of THs, T3 efflux but not T4, is increased. On the other hand, in hypothyroidism, T3 efflux is diminished. Taken together, T3 efflux modulates T3 intracellular concentration.

PO. 048

Genomic and non-genomic intracellular pathways involved in thyroid hormona mediated T lymphoma cell proliferation

Barreiro Arcos ML1, Farías RN2, Klecha AJ1-3, Sterle HA1, Genaro AM11-3, Cremaschi GA1-3

1Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad de Buenos Aires (UBA); 2Instituto Superior de Investigaciones Biologicas (INSIBIO), CONICET, Universidad de Buenos Aires; Buenos Aires, Argentina

Background: Thyroid hormones (THs) exert a broad range of actions on development, growth and cell differentiation including immune cell regulation. These actions involved both genomic and non genomic mechanisms. We demonstrated that THs induce BW5147 T lymphoma cell division, through the activation of the atypical PKCz and the inducible isoform of NOS (iNOS). objectives: To analyze the intracellular signals involved, elucidating the contribution of both genomic and non genomic effects. Methods: Proliferation was evaluated through [3H]-thymidine incorporation; PKC activity in cytosolic and membrane fractions was determined by specific substrate phosphorylation; NOS activity was measured by [14C]-citrulline formation; protein and mRNA levels were determined by western blot and RT-PCR respectively; NF-kB nuclear translocation was measured by EMSA. Results: Selective blockers of acidic and neutral sphingomyelinases, imipramine and GW4869 respectively, inhibited TH effects on proliferation as well as on PKCz activity. TH as well as their cell-impermeable analogs, T3 and T4 coupled to agarose (ag), were able to activate NF-kB. Both T3-ag and T4-ag increase cell proliferation, but to a lesser extent than uncoupled hormones, leading to a rapid translocation of PKC to cell membranes and to ERK phosphorylation. Pre-treatment of cell with a PKCz pseudosubstrate inhibited all these effects. However, HTs-ag were unable to induced iNOS expression at both the protein and mRNA levels. conclusions: These results indicate that THs actions on T lymphoma cell proliferation involved the non genomic activation of PKC, NF-kB and ERK, but the genomic consequent iNOS induction and activation are also necessary for a full effect.


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PO. 049

Efeito da administração de triiodotironina (T3) sobre o dano de DNA em animais com obesidade induzida por dieta

Sibio MT1, Luvizotto RAM1, Olimpio RMC1, Marino J1, Oliveira Jr SA1, Oliveira LRC2, Calvi SA2, Favero DM3, Nogueira CR1

¹Laboratório Experimental de Clínica Médica, Faculdade de Medicina, Unesp – Botucatu-SP, Brasil ²Laboratório de Doenças Tropicais, Faculdade de Medicina, Unesp – Botucatu-SP, Brasil. ³Laboratório de Patologia, Faculdade de Medicina, UNnesp – Botucatu-SP, Brasil-SP, Brasil.

introdução: Aumento da ingestão de calorias ou dieta rica em gordura são determinantes significativos do dano DNA. Concentrações fisiológicas T3 não produzem danos genéticos, enquanto concentrações elevadas podem gerar danos. A literatura não aborda dano DNA em dieta rica em ácidos graxos insaturados (AGI). objetivo: Analisar efeitos da administração de dose suprafisiológica T3 sobre dano DNA em animais submetidos à dieta rica AGI. Métodos: 30 ratos Wistar machos, 30 dias de idade, separados: controle (C), obeso (OB), obesos com dose suprafisiológica de T3 (OBS). Grupo C recebeu ração comercial, enquanto OB e OBS foram submetidos a processo de indução de obesidade, dieta rica AGI (70%), por 28 semanas. Após esse período, OBS recebeu 25 mg/100 g peso animal de T3, durante 2 semanas. Ao final do experimento foram realizados exames bioquímicos e detecção de danos de DNA por meio de teste cometa. estatística: ANOVA complementada com teste de Bonferroni. Nível de significância 5%. Resultados: OB apresentaram aumento de peso, adiposidade, nos níveis de HDL, ácidos graxos livres (AGL) e detecção de danos de DNA e não houve diferença para colesterol, LDL e TG comparados ao grupo C. Os OBS mostraram diminuição de peso e adiposidade, entretanto apresentaram níveis elevados de glicose e dano de DNA comparados ao OB. Não houve diferença para os níveis de AGL, colesterol, HDL, LDL e TG entre esses grupos. conclusão: Dieta rica (AGI), apesar de não alterar o perfil bioquímico, provoca dano DNA. Dose suprafisiológica de T3 mantém níveis de colesterol, TG, provoca hiperglicemia, potencializa produção de danos DNA.

PO. 050

A case study of the thyroid hormone receptor alpha homodimer interface

Ribeiro ICJ1, De Farias RF1, Bampa G1, Neves FAR1, Polikarpov I2, Togashi M1

1Department of Pharmaceutical Sciences, Health Sciences School, University of Brasilia; Brasilia, Brazil; 2Department de Physics and Informatics, São Carlos Physic Institute, University of Sao Paulo; Sao Paulo, Brazil

Thyroid hormone (TH) effect is mediated by thyroid hormone receptors alpha (TRα) and beta (TRb). It has many beneficial effects in different tissues; however, its excess can produce deleterious effects attributed to TRα. TR ligand binding domain (LBD) regulates transcription, cofactor interaction, and dimerization. Dimerization property is influenced by ligand and DNA response element (TRE) to which TR can bind. While TRb can form homodimers, heterodimers, and monomers, TRα can form heterodimers and monomers on TREs. Preference to bind to different TREs can influence TR action through recruitment of distinct transcription complexes. Here, we aimed to characterize TRα dimer interface by introducing point mutations in residues E391, R157, H362, and W364 of the TRα LBD. Functionality of mutated TRs was confirmed through transfections followed by gene reporter assays of the full length native and mutated TRs. Dimerization properties of purified LBDs were observed through native polyacrylamide gel electrophoresis. Contrary to the full length receptor which cannot for homodimers, TRα LBD solely can form homodimers and monomers. Mutations in H362, located in the loop between helix (H) 10 and H11, and E391, located between H11 and H12, seem to favor homodimer formation, reducing significantly monomer formation. Despite the fact that there is a high homology between TRα and TRβ, we still do not understand the structural elements that contribute to ligand specificity for each isoform. Characterizing TRα dimer interface would give us better tools to understand its function and design isoform-specific drugs.

PO. 051

Glucocorticoids prevent thyroid hormone action at the level of the initiation of the immune response. Role of dexam-ethasone on triiodothyronine (T3) effects on mice dendritic cell characteristics

Montesinos MM1, Mascanfroni ID1, Alamino VA1, Susperreguy S1, Masini-Repiso AM1, Rabinovich GA2, Pellizas CG1

1CIBICI-CONICET. Dpto. de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina; 2Laboratorio de Inmunopatología. IBYME-CONICET; Buenos Aires; Argentina

Glucocorticoids (GC) modulate immune responses and are used for autoimune/inflammatory disorders. Several studies emphasized the role of antigen presenting cells (APC) in GC-mediated suppression of immunity. Dendritic cells (DC) are the main APC that stimulate naive T cells to regulate adaptive immunity. Mice DC are generated from bone marrow (immature DC:iDC) and the exposure to pro-inflammatory stimuli (lipopolysaccharide,LPS) generates mature DC (mDC) that stimulate T cells. We demonstrated that GC enhance triiodothyronine (T3)-dependent actions in liver involving an increase of thyroid hormone receptor (TR) β1 expression (Montesinos et al. Life Sciences. 2006;78:2584). Recently, we provided evidence for TRβ1expression and T3 stimulatory action on DC (Mascanfroni et al, FASEB Journal. 2008;22:1032) by a mechanism involving T3 binding to cytosolic TRβ1 and Akt activation (Pellizas et al. RAEM 2008;45:25). We aimed at evaluating the effect of Dexamethasone (Dex: synthetic GC) on T3 action in DC. Mice iDC were pulsed with Dex 10 nM, LPS 100 ng/ml (positive control) or T3 5 nM. We measured TRβ1 expression and Akt-phosphorylation by Western Blot, and DC maturation markers (CD86-CD40) and intracellular IL-12 production by flow cytometry. Results indicated that Dex reduced TRβ1 expression in iDC and mDC by a mechanism that involved GR (it was prevented by a GR antagonist: RU486). The increment in maturation markers and IL-12-producing DC induced by T3 and LPS was abolished by Dex and restored by RU486. T3-induced Akt phosphorylation was inhibited by Dex. These results indicate that GC and T3 mechanisms of action are interrelated in a tissue-specific manner.


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PO. 052

Acute T3 administration reduces polyadenylation of βTSH mRNA of hypothyroid rats: a non genomic action of thyroid hormone

Souza PB, Bruneto EL, Nunes MTLaboratory of Endocrine Physiology, Department of Physiology and Biophysics, Institute of Biomedical Science (ICB), University of Sao Paulo; Sao Paulo, Brazil

Thyroid hormone (TH) biosynthesis is primarily regulated by TSH, a pituitary hormone that consists of two subunits (α and β). The βTSH transcription, in turn, is negatively regulated by T3. Considering that TH also acts nongenomically, and that some of these actions occur at the level of the transcript stability, in which the poly (A) tail length of mRNAs plays an important role, the goal of this study was to evaluate if TH interferes with βTSH mRNA stability, altering its poly (A) tail length. Euthyroid (sham-operated, SO) and thyroidectomized (Tx) male Wistar rats, treated with T3 (100 µg/100 g BW, i.v – SOT3, TxT3) or saline (0.9% NaCl), were used in the study. The rats were killed by decapitation, 30 min after T3 or saline treatment. The pituitaries were excised and used for total RNA extraction. The poly (A) tail length of βTSH mRNA was analyzed by RACE-PAT assay. The present data show that thyroidectomy led to an increase of 40% in βTSH mRNA poly (A) tail length (P < 0.01, TxT3 vs. Tx) 30 min after T3 administration; and that T3 treatment did not induce any alteration in the βTSH mRNA poly (A) tail length in euthyroid rats. The present data indicate that in parallel to its transcriptional action decreasing βTSH expression, T3 acts nongenomically reducing the poly (A) tail length of βTSH mRNA and, as a consequence, its stability, characterizing a non genomic action that seems to be more relevant in hypothyroid states.

PO. 053

Efeito do hormônio tireoideano sobre o conteúdo e translocação do transportador de glicose GLUT4 no tecido adi-poso: possível ação não-genômica do hormônio

Croffi RV, Teixeira SS, Machado UF, Nunes MTLaboratório de Fisiologia Endócrina, Depto. de Fisiologia e Biofísica, ICB, USP; São Paulo, Brasil

introdução: O hormônio tireoideano (HT) controla a expressão de genes específicos interagindo com seu receptor nuclear (TR). Há, também, evidências de ações não genômicas promovidas pelo HT. O GLUT4 é o principal transportador de glicose no musculoesquelético, cardíaco e tecido adiposo. Estudos do nosso laboratório mostraram que o HT transloca GLUT4 para a membrana plasmática (MP) nos dois primeiros tecidos, em apenas 30 min, sugerindo mecanismos não genômicos, efeito que ainda não foi avaliado no tecido adiposo, que tem grande importância no quadro de resistência insulínica. objetivo: Investigar se o HT altera, agudamente, a taxa de translocação (TTG4) e o conteúdo total de GLUT4 (CTG4) em tecido adiposo periepididimal (TAB). Métodos: Ratos Wistar (200 g) tiroidectomizados (Tx) ou não (eutiroideo) receberam os seguintes tratamentos: Salina (0,9%) , T3 (0,3; 1,5; 15 e 100 mg/100 g PC- ev) ou T4 (0,8; 4 e 40 mg/100 g PC, ev), sendo sacrificados após 30 min. O TAB foi processado para obtenção das frações de MP e microssomos, para avaliação do conteúdo de GLUT4, por Western blotting. Resultados: O grupo Tx + salina apresentou redução da TTG4 e do CTG4 vs. grupo eutiroideo. A maior dose de T3 provocou um aumento na TTG4 do grupo eutiroideo. No grupo Tx, as doses 0,3 e 1,5 de T3 aumentaram a TTG4 vs. Tx. O T4 não provocou alterações importantes nesses parâmetros. conclusões: O HT é importante para a manutenção da síntese e translocação do GLUT4 no TAB. O T3 aumenta a TTG4 no TAB por mecanismos não genômicos.

PO. 054

Low triiodothyronine (T3) plasma levels in congestive heart failure (CHF) are associated with other neurohormonal and inflammatory prognostic markers of the disease

Brenta G, Thierer J, Vainstein N, Acosta A, Boero L, Sutton M, Brites FCardiovascular Institute of Buenos Aires (ICBA) School of Pharmacy and Biochemistry, University of Buenos Aires Dr. Cesar Milstein Hospital; Buenos Aires, Argentina

Background: Low plasma T3 levels are considered a prognostic predictor of death in CHF patients. aim: To study any possible association between T3 plasma levels and several cardiac, neurohormonal and inflammatory markers of CHF. Methods: 151 ambulatory CHF patients with ejection fraction < 40% were enrolled. TSH, total T4 and T3 and other cardiac and metabolic parameters were measured. After excluding overt hypothyroid and hyperthyroid patients, 133 patients (114 males; mean age, 63.2 years) remained and were followed for 2 years. Results: In simple linear regression, T3 was inversely related to New York Heart Association (NYHA) class III-IV, p = 0.016; log transformation of NT-pro BNP, p = 0.001 and adiponectin, p = 0.01, while it was directly related to haemoglobin, p = 0.004; creatinine clearance, p = 0.0001; log transformation of sulphate-dehydroepiandrosterone (S-DHEA), p = 0.027; and 6 minute walking test (mts), p = 0.009. When dividing T3 in tertiles, age, NYHA class IIII-IV, haemoglobin, azoemia, creatinine clearance, log transformation of NT-pro BNP and S-DHEA, adiponectin, 6 minute walking test (mts), bioelectrical impedance phase angle, and amiodarone use, were significantly different between the lowest T3 tertile and the rest of the population. Death rate was higher in the lowest tertile: 28.9% vs. 13.6% (HR 2.4, CI95% 1.1-5.3, p = 0.026). In multiple logistic regression the lowest tertile of T3 was independently associated with a marker of membrane damage, the bioelectrical impedance phase angle (OR = 2.81, CI95% 1.3-6.1, p = 0.009), and the log transformation of DHEA (OR = 0.58; CI95% 0.37-0.92, p = 0.022). conclusion: We have demonstrated an association between T3 plasma levels in the lower range and other deranged hormonal and metabolic parameters in CHF patients. The pathophysiologic role of T3 in this association remains to be studied.


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PO. 055

TSH increases nitric oxide synthase III expression through a PKA-dependent AKT activation

Fozzatti L, Nicola JP, Nazar M, Velez ML, Lucero AM, Pellizas CG, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunologia, CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

Nitric oxide (NO) is a free radical that mediates signal transduction and influences a wide variety of biological processes. It is generated by three different nitric oxide synthase (NOS) isoforms (I-III). Although all NOS enzymes have been identified in the thyroid cell, NOS III is the highest expressed. We reported that NO acts as a regulator of the TSH-induced gene expression and that TSH is able to increases NO production and NOS III mRNA expression. The aim of this work was to analyze the signal pathway involved in the TSH-induced expression of NOS III in the thyroid cells FRTL-5. TSH stimulated NOS III protein expression in a time and concentration dependent manner. We evaluated a possible post-transcriptional effect of TSH on NOS III protein stabilization. A significant increase in NOS III protein half-life was induced by TSH treatment. In order to examine the signal pathway involved, we measured the effect of TSH on NOS III protein expression in the presence of different kinase inhibitors. We observed a significant inhibition of the TSH-induced protein up-regulation in presence of PKA and Akt inhibitors. As Akt is canonically activated by PI3K, we evaluated the effect of PI3K inhibitors on the TSH-increased NOS III expression but no evident blockage was observed. When we evaluated Akt phosphorylation in response to TSH, a TSH-dependent Akt phosphorylation that involves PKA activity was found. In conclusion, our results provide evidence of a novel regulation of NOS III expression by TSH involving a PKA-mediated activation of the Akt pathway.

PO. 056

Síndrome eutiroideo enfermo en diabetes tipo 2

Juarez XE, Diaz SADepartamento de Medicina Interna, Hospital Nacional San Juan de Dios de San Miguel; El Salvador

El síndrome eutiroideo enfermo (SEE), es un estado patológico existente en los pacientes que cursan con enfermedades sistémicas, en quienes los valores séricos de hormonas tiroideas están alterados en ausencia de enfermedad tiroidea. Aunque ésta entidad no es muy bien conocida, estudios recientes han demostrado que pacientes con enfermedades críticas y con alteraciones en las pruebas de función tiroidea, tienen un pronóstico malo. Los pocos estudios en pacientes con diabetes con diabetes mellitus tipo 2 (DM2) han demostrado que el riesgo de presentar este síndrome se incrementa con la duración de la diabetes, comorbilidades asociadas y con un inadecuado control metabólico, y su presencia constituye un factor de mal pronóstico en estos pacientes. El objetivo de este estudio es evaluar la asociación entre SEE y el control metabólico (HbA1c) en pacientes con DM2 Tomamos una muestra constituída por 30 pacientes diabéticos tipo 2 hospitalizados en los Servicios de Medicina Interna del Hospital San Juan de Dios de San Miguel, El Salvador. A quienes se les realizó una evaluación clínica, medición de hormonas tiroideas (T3 y TSH) y HbA1c. La prevalencia de SEE fué de 60% de los cuales el 72.2% reunió características para SEE leve (únicamente T3 baja). Valor mucho más alto si se compara con otros estudios reportados en la literatura realizados en pacientes ambulatorios La conclusión de nuestro estudio fué que la prevalencia de SEE en pacientes con DM2 es alta y está asociada a un mayor tiempo de enfermedad, inadecuado control metabólico (HbA1c) y a las complicaciones crónicas de la enfermedad, así como a la gravedad de las mismas. Su presencia también constituye un factor de mal pronóstico en estos pacientes.

PO. 057

Iodine excess increases seleproteins expression in rat thyroid

Fuziwara CS, Raimundo SG, Leoni SG, da Silva MJ, Ricarte-Filho JC, Kimura ETDepartment of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo; Sao Paulo, Brazil

Background: Classically, iodine excess inhibits thyroid hormone synthesis (Wolff-Chaikoff Effect). Despite the number of studies that have tried to elucidate iodine role in thyroid auto-regulation, the molecular mechanisms of its action remain unclear. Using SAGE (Serial Analysis of Gene Expression) methodology, we revealed a subset of genes up-regulated by high- concentration-iodide treatment in rat thyroid follicular PCCl3 cells, which includes the selenoprotein Gpx2 and Txn1. These proteins participate in the regulation of redox status of cells during H2O2-dependent hormone biosynthesis, protecting cells from oxidative damage. objectives: investigate in vivo the role of selenoproteins in the acute effect of iodine overload. Methods: female wistar rats (~200g) were divided into groups (n = 48): 24, 48 and 72 hours after i.p injection of 2000 mg of NaI and control that received saline. Thyroids were cirurgically removed and total RNA extracted. Gene expression was analyzed from 100 ng of cDNA by real-time PCR using specific primers for Gpx2 and Txn1, and Rpl19, an internal control. Results: high-dose-iodide induces Gpx2 and Txn1 mRNA expression in a time-dependent manner with maximum increase at 72 hours and 48 hours for Gpx2 (CTR: 2.13 ± 0.71; I 24h: 2.82 ± 0.50; I 48h: 8.95 ± 3.08; I 72h: 18.50 ± 6.11) and Txn1 (CTR: 4.89 ± 0.62; I 24h: 5.07 ± 0.69; I 48h: 10.30 ± 0.27; I 72h: 7.71 ± 1.17), respectively. conclusions: the increase of Gpx2 and Txn1 expression indicates an important role for these proteins in the maintenance of homeostasis in response to oxidative stress induced by iodide excess, thus extending our comprehension of the molecular mechanisms underlying iodine action. Support: CNPq, Fapesp, Capes.


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PO. 058

Detecção de fitoquímicos capazes de promover o aumento da captação tireoidea de iodeto in vitro e in vivo

Santos MCS, Gonçalves CFL, Souza ECL, Braga WMO, Ginabreda MGP, Ferreira ACF, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brasil

introdução: Durante a progressão tumoral dos carcinomas diferenciados da tireoide há perda das características de diferenciação celular, o que torna ineficaz o tratamento convencional com radioiodoterapia. Assim, há grande interesse na descoberta de substâncias capazes de aumentar a captação tireoidea de radioiodo. Metodologia: Inicialmente, realizamos um screening de nove fitoquímicos purificados e detectamos atividade biológica estimulatória sobre a captação de iodeto de dois compostos (A e B). Cultivamos a linhagem PCCL3 em Coon’s Modified Ham’s F12 suplementado com 5% de soro fetal bovino, insulina (10 mg/mL), transferrina (5 mg/mL) e TSH (1 mU/mL). As células foram tratadas com as substâncias A e/ou B durante três dias. Após esse período, medimos a captação específica de iodeto depois de 45 minutos de incubação com Na125I. Para o estudo in vivo foram utilizados ratos Wistar machos pesando entre 200-250 g, tratados com a dose de 10 mg/kg por via subcutânea, durante cinco dias. Os animais receberam Na125I 15 minutos antes de serem eutanasiados e as tireoides foram excisadas para medida da radioatividade. As substâncias A e B testadas foram capazes de promover aumento significativo da captação tireoidea de iodeto in vitro (1,86 e 2,46 vezes em relação ao controle) e in vivo (1,46 e 1,71 vezes). conclusão: Nossos resultados mostram que essas substâncias podem modular positivamente o NIS, o que pode ser de grande relevância clínica. No momento estamos investigando o mecanismo pelo qual essas substâncias agem e os dados iniciais estão sendo submetidos a depósito de patente de descoberta de novos fármacos.

PO. 059

Substitution of serine for proline in the active center of type 2 iodothyronine deiodinase substantially alters its in vitro biochemical properties but not its function in vitro

Goemann IM1, Harney JW2, Maia AL1, Larsen PR2

1Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Porto Alegre, Brazil; 2Thyroid Section, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School Boston; Massachussetts, USA.

Thyroid hormones undergo peripheral deiodination, being activated by iodothyronine deiodinases type 1 and 2 (D1 and D2). Studies have demonstrated that the D2 “catalytic efficiency” (ratio of catalytic activity in intact cells to that found in vitro) at different FT4 concentrations is much higher than that of D1, but the reasons for this striking difference are not yet completely understood. The substitution of a serine (as in D1) for a proline at position 135 of D2 (P135S-D2) could be responsible for some of the biochemical differences between D2 and D1. objective: To compare the effects of the P135S mutation in D2 on its function when expressed in cells with endogenous D2 cofactor (in vivo activity) with its in vitro properties. Methods: HEK-293 cells were transfected with D2 (wtD2) or P135S-D2 and incubated with I125T4 at 2, 20 and 200 pmol FT4. This model mimics the physiological conditions of cofactor and FT4. Results: In vitro, the P135S-D2 Km (T4) was 780 nM, 400X higher than that of wtD2 with apparent Vmax which were about 100X higher at the same conditions. Despite these differences, the rate of T4-to-T3 conversion in cells at low, normal and high FT4 concentrations was similar as with wtD2. conclusion: Our results demonstrate that the P135S mutation alters the in vitro biochemical properties of D2 making it like D1. However, its function in vivo is not changed. We conclude that the factors critical for the in vivo activity of the deiodinases may not be accurately reflected by their in vitro biochemical properties.

PO. 060

O iodo altera a expressão do mRNA de pendrina: estudo in vitro e in vivo

Calil-Silveira J, Serrano-Nascimento C, Nunes MTDepartamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo; São Paulo, Brasil

introdução: O iodo é fundamental para a síntese de hormônios tireoideanos. Ele é captado pelo Co-transportador Na + /I- e transportado para o lúmen folicular através da Pendrina (PDS). Há evidências de que, quando em excesso, o iodo torna-se deletério, comprometendo o estado funcional tireoideano. Considerando-se que a estabilidade de alguns mRNAs que codificam proteínas envolvidas com o transporte de oligominerais é modificada por alterações no aporte destes, nosso objetivo foi avaliar se a administração aguda de doses elevadas de iodo altera a expressão do mRNA de PDS. Métodos: Ratos machos Wistar receberam metimazol dissolvido em água de beber, por 4 dias, e foram divididos nos grupos controle (C) e iodo (I), que receberam salina ou NaI (2 mg/dia, ip). Após 30 min, 1 e 24 h extraiu-se o RNA total da tireoide, e a expressão de PDS foi analisada por Northern Blotting. Nos estudos in vitro, células PCCl3 foram tratadas ou não com 10-3 M de NaI, por 30 min, 1 e 24 h. A expressão de PDS, nesse modelo, foi avaliada por Real-Time PCR. Resultado: O conteúdo de mRNA de PDS mostrou-se significativamente aumentado nos grupos tratados com iodo, em ambos os modelos estudados. conclusão: A rápida regulação da expressão gênica da PDS (a partir de 30 min) pelo iodo indica que, diante de seu excesso, mecanismos pós-transcricionais são desencadeados para aumentar seu efluxo da célula, na tentativa de protegê-la dos seus efeitos deletérios. Esse dado sugere uma ação direta do iodo regulando a expressão gênica da pendrina.


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PO. 061

A novel role of the NFKb transcription factor in the TSH-regulated thyroid gene expression

Nicola JP, Nazar M, Mascanfroni ID, Pellizas CG, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

The nuclear factor-kB (NFkB) transcription factors are key regulators of immune response, cell survival, proliferation and gene expression. NFkB transcription factors function as dimers of five different subunits including p65, RelB, c-Rel, p50 and p52. NFkB family is an ubiquitously expressed transcription factors that can be activated in response to different signals. Activation of NFkB in thyroid cells by TSH or stimulating TSHR antibodies has been reported previously, although the function of NFkB in normal thyroid physiology has not been explored. The objective of this study was to analyze a possible role of NFkB in the TSH-induced gene expression in the thyroid cell. We observed a nuclear recruitment of NFkB subunits in response to TSH in FRTL-5 cells, suggesting NFkB activation. Pharmacological inhibition of PKA blocked the TSH-induced NFkB activation. The presence of NFkB inhibitors significantly reduced the TSH-induced expression of the genes involved in thyroid hormone biosynthesis, Na +/I- symporter, thyroperoxidase, DUOX2 and thyroglobulin. The blockage of NFkB signaling reduced the TSH-stimulated mRNA and promoter activation levels indicating a transcriptional event. Bioinformatical analysis revealed the presence of NFkB consensus sites in the promoter regions of these differentiation genes. Chromatin immunoprecipitation assay confirmed the binding of the NFkB subunit p65 to the promoter region of all these genes. Silencing of p65 expression corroborated its original role in the TSH-induced gene expression. In conclusion, these findings provide evidence that NFkB could constitute a novel mediator of crucial importance in the TSH-induced gene expression, a relevant finding of potential physiological and pathophysiological implication.

PO. 062

Efeito da ovariectomia e do tratamento com 17β-estradiol sobre a função tireoidea e a ativação da via Ras-pERK em tireoides murinas

Pantaleão TU, Mendonça KT, Mousovich Neto F, Rosenthal D, Corrêa da Costa VMLaboratório de Fisiologia Endócrina, Instituto de Biofísica Carlos Chagas Filho, UFRJ; Rio de Janeiro, Brasil

introdução: A via Ras-pERK é proliferativa em diversos tipos celulares e as disfunções da tireoide são mais frequentes em mulheres. objetivos: Avaliar o efeito da ovariectomia, com ou sem reposição de estradiol (E2), sobre a ativação da via Ras-pERK e sobre a função tireoidea. Métodos: Fêmeas Wistar foram divididas em: controle (C), ovariectomizada (OVX), OVX com reposição diária (sc) de E2, 0,7 µg/100 g pc (OVX + 0,7) ou 14 µg/100 g pc (OVX + 14), e C tratadas com E2 14 µg/100 g pc (C + 14), por 21 dias. E2, T3 e T4 séricos foram dosados por RIEs. As tireoides foram homogeneizadas e 50 ou 100 µg de proteína usadas para determinar a expressão de RAS, pERK, ERK total e actina. Resultados: Os níveis séricos de E2 aumentaram significativamente com a maior dose e diminuíram com a castração, (C: 31,01 ± 10,63; OVX: 15,69 ± 2,70; OVX + 0,7: 55,01 ± 12,19; OVX + 14: 690,9 ± 109,3; C + 14: 740,0 ± 112,0 pg/ml). T4 sérico diminuiu significativamente no grupo OVX + 0,7, enquanto o T3 aumentou apenas no grupo intacto tratado com E2 na maior dose. Os pesos relativos tireoideos não variaram entre os grupos. A expressão de RAS e de pERK não diferiu entre os grupos (C: 0,95 ± 0,38; OVX: 1,44 ± 0,55; OVX + 0,7: 1,33 ± 0,62; OVX + 14: 1,12 ± 0,28; C + 14: 1,31 ± 0,13 ua [razão RAS/actina]) e (pERK/ERK total: (C: 0,99 ± 0,17; OVX: 1,06 ± 0,09; OVX + 0,7: 1,34 ± 0,22; OVX + 14: 0,96 ± 0,08; C + 14: 0,87 ± 0,06 ua), respectivamente. conclusões: Os níveis séricos de E2 não influenciaram a massa da glândula tireoide, nem a via RAS-pERK glandular. Assim, embora a função tireoidea pareça ser modulada por E2, outros estudos são necessários para a melhor compreensão dessa modulação.

PO. 064

Eliminacion de la deficiencia de yodo en Paraguay y riesgo de exceso de yodo

Ovelar EC, Redondo J, Zarza Z, González N, Jara J, Pretell EAInstituto Nacional de Alimentación y Nutrición, Ministerio de Salud Pública y Bienestar Social; Asunción, Paraguay

antecedentes: La deficiencia de yodo es un problema natural en todo el territorio nacional. En 1988 la prevalencia de bocio fue 48.6% y la mediana de yodo urinario 72 µg/L. La estrategia del Programa de Control de los DDI se basa principalmente en el aseguramiento de la yodación universal de la sal para consumo humano y el fomento de su consumo, y el monitoreo del yodo en la sal y en la orina. objetivo: Evaluar la situación actual de la nutrición de yodo en Paraguay. Métodos: El contenido de yodo en la sal ha sido monitoreado a nivel de centros de producción, boca de expendio y hogares; el análisis ha sido por método cuantitativo. La nutrición de yodo en la población ha sido evaluada mediante el análisis del yodo urinario. Resultados y conclusiones: Se ha logrado la yodación universal de la sal y la eliminación de la deficiencia de yodo desde 1996. El nivel oficial de yodación (40-60 ppm) en los centros de producción se cumple en 34% de la sal y en el 40% sobrepasó el nivel de 60ppm. En boca de expendio más del 95% contiene más de 15 ppm, pero en 73% está sobre 40 ppm. Más de 90% de hogares consume sal yodada, cuyo contenido de yodo está sobre 40 ppm en 75% de la sal. La mediana de la yoduria se ha mantenido sobre 300 µg/L desde el 2001. Estos resultados demuestran la eliminación de la deficiencia de yodo y el surgimiento del riesgo de exceso de yodo en la población.


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Sustained elimination of iodine deficiency in Peru for about 15 years

Pretell EA, Higa AMMinistery of Health, Cayetano Heredia Peruvian University and International Council for Control of Iodine Deficiency Disorders; Lima, Peru

Background: Severe iodine deficiency was recognized long ago in the sierra and the jungle, but received little attention. New studies in the 60s demonstrated not only the persistence of severe deficiency, but mainly that it is the main cause of preventable brain damage. In 1983 a program for its control was founded and fully implemented in 1986. Objectives. To reach the goals of USI and sustained elimination of IDD. Methods: The Program´s strategic plan of action included immediate protection of two million population at high risk with iodized oil, and progressive improve of production, quality and consumption of iodized salt, while a well-trained national network, an intensive communication and advocacy program, and a systematic monitoring of iodine in salt in the population were implemented. Results and conclusions: The coverage of the population iodized salt demand rose from 57% at the starting point to above 100% since 1995, adequately iodized salt is consumed by more than 90% of households since 1998. The median urinary iodine rose from 71 ug/l to 139 µg/L nine years later and the iodine nutrition has been maintained normal for over 13 years (median urinary iodine above 100 µg/L). Goiter prevalence significantly decreased by the sixth year follow up. Key factors for the Program´s success have been monitoring and surveillance, effective communication, and support of the Ministry of Health and the salt industry. In conclusion, Peru has succeeded in the sustained elimination of IDD, preventing the brain damage in 600 thousand newborn each year.

Thyroid nodules & CanCer

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Patients with familial papillary thyroid cancer have a similar outcome than those with sporadic tumors

Pitoia F, Cross G, Salvai ME, Nuñez S, Haseitel M, Abelleira E, Niepomniszcze HDivision of Endocrinology, Hospital de Clínicas, University of Buenos Aires; Buenos Aires, Argentina

In the familial form of papillary thyroid cancer (FPTC), two or more members of the same family are affected with papillary thyroid cancer (PTC). Prevalence is around 5% of all PTC. The aim of this study was to compare the clinical behavior and the outcome of 16 subjects with FPTC from seven unrelated kindred with that observed in 160 subjects with non familial PTC from our database. None of the included subjects had been exposed to radiation. In patients with FPTC, mean age at diagnosis was 41.7 ± 13 vs.. 44 ± 16 years in sporadic PTC, (p = ns) and female/male ratio was 7/1 vs.. 6/1, respectively (p = ns). Malignancy was bilateral in 6/16 (38%) vs.. 38/160 (24%), respectively, (p = 0.03). Lymph node metastases were diagnosed in 8/16 (57.1%) of FPTC and in 62/160 (39%) of sporadic PTC (p = 0.02), and distant metastases in 2/16 (14.3%) vs. in 26/160 (16%), respectively, (p = ns). Considering the outcome, in the FPTC group, 9 (56.2%) patients were rendered free of disease, one patient died (6%) and 6/16 (37.5%) had persistent disease. In the sporadic PTC group, 87 (54%) were considered free of disease, 11 (7%) subjects died, and 62 (38%) had persistent disease. There were no statistically significant differences when both groups were compared. In conclusion, the bilateral tumor occurrence and the existence of lymph node metastasis were the only differences observed between FPTC and sporadic PTC. This situation seemed not to alter the compared outcome between these two groups of PTC in the long term follow-up.

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Patients with insulin resistance have less aggressive papillary thyroid cancers

Rezzónico JN1, Rezzónico M1, Pusiol E1, Pitoia F2, Niepomniszcze H2

1Centro Privado de Endocrinología, Mendoza; 2Division of Endocrinology, Hospital de Clínicas. UBA; Buenos Aires, Argentina

Patients with insulin resistance (IR) have larger thyroid glands and a higher incidence of thyroid nodules (Thyroid, 2008, 18:461-464). Moreover, we subsequently showed that patients with differentiated thyroid carcinoma (DTC) also have a higher frequency of IR. The aim of this study was to compare the TNM stage in 14 patients with papillary thyroid cancer (PTC) and IR, with that observed in another 16 patients with PTC without IR. Fourteen women with PTC and IR [Group 1; G1], mean age 45.1 ± 11.1, and 16 women with PTC and no IR (Group 2; G2), mean age 43.4 ± 13.9, were investigated for the TNM stage at diagnosis of PTC. The diagnosis of IR was made when the HOMA-IR index was higher than 2.5. To facilitate analysis, T (tumor size) was grouped as follows: T 1 + 2 and T 3 + 4. Results: Age was not different between groups. Weight was higher in G1 vs. G2 as expected (75.9 ± 17 vs. 59.9 ± 8.1, respectively; p < 0.01). T 1 + 2 was observed in 92.9% of G1 vs. 87.5% of G2 (p = ns), T 3 + 4 in 7.1% of G1 vs. 12.5% of G2. Lymph node metastasis were present in 14.3% of G1 and in 50% of G2 (p < 0.04), while distant metastasis were 7.1% in G1 vs. 12.5% of G2, (p = ns). conclusion: Patients with papillary thyroid cancer and IR have a lower frequency of lymph node metastasis when compared with no insulin resistant patients. This situation would suggest that those “genuine” thyroid cancers (not stimulated by IR) might behave more aggressively than those possibly generated by the proliferative stimulus of insulin.


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Caracteristicas del bocio nodular benigno en pacientes evaluados en consultorios privados de la ciudad de Buenos Aires

Antunez PB1-2, Licht SD2

11ra Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2055 (CP 1405); 2Sanatorio Trinidad Mitre, B. Mitre 2555 (CP 1230); Buenos Aires, Argentina

Existen diferencias en etiología y manifestaciones del bocio nodular en diferentes poblaciones. Se evaluaron y correlacionaron características varias de pacientes eutiroideos con nódulos tiroideos benignos. Método: Se evaluaron características semiológicas, ecográficas y TSH/TPO, y diagnóstico por PAAF de pacientes eutiroideos con bocio nodular benigno, atendidos en Buenos Aires, Argentina, entre 2004 y 2008. Resultados: Se evaluaron 143 pacientes eutiroideos con bocio nodular benigno, 132 mujeres y 11 hombres; la edad fue 47,0 ± 12,1 años. El diagnóstico por PAAF fue bocio coloide, tiroiditis crónica, hiperplasia nodular o quiste tiroideo (N = 88, 27, 27 y 11, respectivamente). En 106/143 (69,3%) el tamaño palpatorio coincidió con diferencia < 5 mm con el medido ecográficamente, y resultó mayor el valor ecográfico en 44 pacientes; el promedio de los diámetros mayores fue 22,07 ± 0,6 mm entre los que coincidían palpación y medición ecográfica, y 18,15 ± 2,5 mm entre los que el tamaño ecográfico fue mayor, con diferencia significativa en bocios coloides y tiroiditis crónicas. Hubo correlación significativa positiva entre de TSH y diámetro mayor ecográfico solamente entre los pacientes con tiroiditis crónica (R = 0,419, p < 0,05).). Tuvieron autoinmunidad positiva el 92,6% de los pacientes con tiroiditis crónica (resto < 25%). conclusiones: En nuestra población, el tamaño evaluado palpatoriamente de los nódulos tiroideos coincidió con el medido ecográficamente en 69,3%; la discordancia fue mayor en bocios coloides y tiroiditis crónicas; hubo correlación significativa positiva entre TSH y diámetro mayor ecográfico solamente en las tiroiditis crónica, y la casi totalidad de pacientes de éstos tuvieron autoinmunidad positiva.

PO. 068

Alta incidência de alterações morfológicas tireoidianas em acromegálicos

Assupção CB, Carvalho GM, Fernandes-Caldato MC, Oliveira RGUniversidade do Estado do Pará, Hospital Universitário João de Barros Barreto (HUJBB); Teresina, Brasil

introdução: Acromegalia é uma doença crônica e insidiosa que resulta da produção excessiva de hormônio do crescimento. A prevalência de distúrbios tireoidianos dentre acromegálicos é aumentada em relação à população geral, variando de 18% a 92%. Com a ultrassonografia, nota-se que a prevalência de bócio na acromegalia é alta e em torno de 78% e 55,4% dos bócios são nodulares. Alguns autores sugerem que tumores da tireoide podem ser estimulados pelo aumento dos níveis de IGF-1. objetivos: Avaliar a morfologia e a função tireoidiana em pacientes acromegálicos atendidos no Ambulatório de Endocrinologia do HUJBB. Métodos: Foram estudados 20 pacientes acromegálicos em acompanhamento no Ambulatório de Endocrinologia, por meio de dosagens séricas de GH, IGF-1, T4L, TSH, anti-TPO e antitireoglobulina e ultrassonografia de tireoide, os pacientes com nódulos acima de 8 mm, foram submetidos à PAAF. Resultados: Foram encontradas alterações tireoidianas em 90% dos pacientes, nos quais não se observaram, no entanto, distúrbios funcionais significativos. As alterações morfológicas encontradas foram: parênquima tireoidiano heterogêneo em 90%, bócio em 55% e nódulos em 55%. Tais alterações podem ser concomitantes e foram mais frequentes no grupo de pacientes com acromegalia não controlada. Observou-se também um aumento progressivo na quantidade de nódulos à proporção que aumenta o tempo estimado de sintomas da acromegalia. Os achados citológicos foram benignos em 60%, suspeitos em 20% e não diagnóstico em 20%. Não houve caso de malignidade comprovada. conclusão: Os pacientes acromegálicos têm maior predisposição para alterações da morfologia tireoidiana.

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Radioiodine treatment of childhood differentiated thyroid cancer (DTC) did not increase the risk of a second primary malignancy or of delayed puberty but resulted in azospermia in one patient

Sztal-Mazer S, Cardoso-Demartini A, Nesi S, Mesa Jr C, Lacerda L, Graf HUnidade de Endocrinologia Pediátrica (UEP), Hospital de Clínicas do Universidade Federal do Paraná (UFPR); Curitiba, Brazil

Background: While radioactive iodine (radioiodine) treatment for DTC increases second primary malignancy risk in adults, evidence in children is scant. Oligospermia in some men, and azospermia in one child, have also been described despite publications to the contrary. Furthermore, childhood cancer survivors generally suffer puberty disturbances; however no specific documentation exists in DTC patients treated with radioiodine. objectives: To determine whether radioiodine affects puberty, or results in second primary malignancy in children with DTC. Methods: Retrospective observational single centre study. Results: After a mean 6.25 years (range 2-13 years), DTC, diagnosed in 15 children under 13 years, is currently in remission or stable. Soon after surgery, radioiodine (mean 149.3mCi) was administered. Total dose ranged from 29.9-900mCi (mean 293.3mCi). Puberty onset was normal in all except one girl (SB) who received pelvic irradiation for a congenital teratoma which predated DTC, and a boy (LJL) with constitutional delay and a positive family history. Both received gonadal steroids. Eleven, including LJL, developed unremarkably; 2 are currently developing normally; while SB requires ongoing hormonal replacement. In another boy, development stalled after a timely onset of puberty. Investigations revealed hypergonadotrophic hypogonadism necessitating intramuscular testosterone. Leydig cell function recovered 2½ years later however subsequent sperm analysis proved azospermia. Thus far, no second primary malignancies have developed, albeit without specific investigations, though 7/15 patients have regular neck and/or chest imaging. conclusion: In our childhood DTC case series, radioiodine did not delay puberty or, as yet, contribute to second primary malignancy. Importantly, one boy suffered transient hypogonadism and permanent azospermia.


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Expression of vascular endothelial growth factor-A (VEGF-A) and its receptor (VEGFR-2) in medullary thyroid carcinoma

Capp C, Siqueira D, Wajner SM, Meurer L, Assis Brasil B, Maia ALThyroid Section, Endocrine Division and Pathology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Porto Alegre, Brazil

Background: Vascular endothelial growth factor (VEGF-A) plays a key role in angiogenesis, an essential step in tumor growth. VEGF-A expression is upregulated in the majority of human tumors, where it stimulates proliferation, migration and survival of endothelial cells by binding to tyrosine kinase (TK) receptors. Medullary Thyroid Carcinoma (MCT) is a C-cell neoplasia accounting for 5-8% of thyroid tumors. Cirurgical resection is the only treatment available and the therapeutic approach in metastatic disease is limited. Recent studies have suggested that TK inhibitors can be used as an alternative therapy in select cases. However, data about expression of VEGF-A and its receptors, as wells as its correlation with clinical presentation in MCT are scarce. objectives: To evaluate VEGF-A and VEGFR-2 expression in MCT samples and correlate with disease presentation. Methods: Thirty-four paraffin-embedded MTC samples were evaluated for VEGF-A and VEGFR-2 expression using immunohistochemistry (antibodies: VEGF-A: sc-152 and VEGFR-2: sc-6251, Santa Cruz Biotechnology, Inc). Results: VEGF-A and VEGFR-2 expression was positive in 94% (32/34) and 91% (31/34) of samples, respectively. There was no differences in VEGF-A or VEGFR-2 expression in sporadic vs. hereditary tumors (p = 0.37 and p = 0.51), age at diagnosis (p = 0.24 and p = 0.07), gender (p = 0.66 and p = 0.24) or tumor invasiveness (p = 0.72 and p = 0.85). Interestingly, we observed a significant correlation between VEGF-A intensity and calcitonin levels at diagnosis (P = 0.02). conclusion: This study demonstrated that VEGF-A and VEGFR-2 are over expressed on MCT. Although VEGF-A has been positively associated with calcitonin levels, overall, these findings do not seem to be correlated with disease progression.

PO. 071

Metástase óssea como apresentação inicial do carcinoma diferenciado da tireoide

Balarini LD, Blummenberg S, Cremasco T, Dias EO, Freitas LV, Mendes T, Kaskus LE, Renaux L, Santos JG, Silva GB, Santos JB, Sasson PServiço de Endocrinologia do Hospital Servidores do Estado, Rio de Janeiro; Rio de Janeiro, Brasil

As metástases ósseas são a forma mais comum de tumores ósseos malignos. Podem ser a primeira manifestação do carcinoma diferenciado de tireoide (CDT), porém é muito raro. Relatamos o caso de uma paciente sem história prévia de doença tireoidiana, cujo achado inicial era metástase na coluna torácica. Relato de caso: Sexo feminino, 61 anos, procurou HSE, com queixas de dor toracolombar e dificuldade de deambulação desde outubro/2007. Relatava ooforectomia esquerda por neoplasia seromucinosa papilífera em abril/2007. exames: Cintilografia óssea-hiperfixação em projeção de T4-5-11-12. TC coluna-lesão lítica insuflante em corpo vertebral de T11 com expansão para pedículo direito e região paravertebral. Biópsia da vértebra-carcinoma metastático, imunoistoquímica-origem tireoidiana. Tireoide no exame físico sem nódulos. USG cervical-nódulos hipoecogênicos em LD 1,2 x 1,0 x 0,8 cm com pequena vascularização central e LE 1,3 x 0,9 cm com calcificação anelar e outro 1,1 x 1,0 cm ambos sem vascularização. Tg > 1000 ng/ml. Realizada tireoidectomia total. Histopatológico-carcinoma folicular no menor nódulo do LE com invasão de cápsula e angioinvasão. Discussão: Incidência de metástase óssea varia de acordo com o grau de diferenciação e o subtipo histológico do carcinoma de tireoide. O carcinoma folicular é o que mais se dissemina para os ossos entre os CDT, com uma frequência de 7%-28% e o papilífero de 1,4%-7%. Osso é o segundo sítio de metástase a distância, sendo o primeiro o pulmão. Importante ressaltar neste caso: 1-exame físico da tireoide era inexpressivo; 2-nódulo maligno não era o mais suspeito ao USG e no ato cirúrgico; 3-concomitância de duas neoplasias primárias-ovário e tireoide. conclusão: Embora seja rara, a metástase óssea pode ser manifestação inicial do CDT e, na presença de metástase com sítio primário oculto, essa glândula também deve ser investigada. Referência: Muresan MM, et al. Bone metastases from differentiated thyroid carcinoma. Endocrine-Related Cancer. 2008;15:37-49.

PO. 072

Cáncer de tiroides detectado en el embarazo

Cabezón CA, Carrizo CServicio de Endocrinología, Metabolismo y Medicina Nuclear, Hospital Italiano; Buenos Aires, Argentina

Se ha reportado mayor frecuencia de nódulos y cáncer de tiroides en el embarazo. objetivo: Evaluar en nuestra población las características del cáncer diferenciado de tiroides detectado en el embarazo (CDTE). Métodos: se evaluaron retrospectivamente historias clínicas de 23 mujeres con CDTE. Se dividió en grupos según momento de consulta: Grupo I (GI) n = 11, consultaron intraembarazo; diagnóstico de CDTE intragesta. Grupo II (GII) n = 12, consultaron post-parto por nódulo detectado intraembarazo. Se realizó punción aspiración tiroidea (PAF) al momento de consulta. Resultados: Edad: 31.8 ± 4.05 años. Diagnóstico por PAF: 20 carcinoma papilar, 3 proliferación folicular. Se realizó tiroidectomía 14.5 ± 10.4 meses post-detección: histología: carcinoma papilar en todos. La ablación fue alejada del parto y lactancia. Seguimiento: 5.6 ± 4.2 años. No hubo diferencias significativas en edad ni en tiempo de seguimiento entre grupos. Detección del nódulo: GI 54.5% 1º trimestre y GII 100% 2º-3º trimestre. El tamaño tumoral fue mayor en el GII: 24.8 ± 12.7 vs. GI: 14.7 ± 3.2 mm, p = 0.039. Lapso entre detección del nódulo y cirugía: GI 7.2 ± 3.5 vs. GII 21.3 ± 10.1 meses, p = 0.002. Hubo correlación positiva entre tiempo de detección del nódulo y tamaño tumoral (r: 0.63, p = 0.01). Estadíos (E): GI: 54.4% EI (intratiroideo), 36.3% EII (metástasis ganglionares), 9% EIII (extensión extratiroidea) y GII: 33.3% EI, 50% EII, 16.7% EIII. Todas las pacientes (excepto una del GII) se encuentran libres de enfermedad. conclusiones: El tamaño tumoral y el estadío tumoral fueron mayores en las pacientes del GII. El tamaño tumoral correlacionó positivamente con el tiempo de demora en la consulta. Esta demora (GII) puede deberse a la detección del nódulo cercana al parto con postergación de su estudio.


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Microcarcinoma papilífero em hipertireoidismo

Blumemberg S, Renaux L, Sasson P, Mansur V, Kaskus L, Góis C, Frota D, Jesus R, Panernari THospital Servidores do Estado do Rio de Janeiro; Rio de Janeiro, Brasil

O caso apresentado é de um paciente, sexo feminino, 44 anos, atendida em 2004 com hipertireoidismo, bócio e questionável oftalmopatia, ocorrendo compensação do quadro com uso de antitireoidianos. Em consulta em 2007, chamou a atenção a palpação de um nódulo de 2,5 cm em lobo direito (LD), com a ultrassonografia mostrando um bócio multinodular (BMN) e a cintilografia com I131 evidenciando uma região hipercaptante em terço médio de LD, com o restante da glândula hipocaptante. Com a suspeita entre o bócio nodular tóxico (BNT) e o bócio difuso tóxico (BDT) associado a nódulos, optou-se por tireoidectomia. Foi realizada lobectomia à direita, cujo exame histopatológico revelou carcinoma papilífero em LD em bócio difuso hiperplásico. Serão abordados os fatores envolvidos na patogênese do câncer como TSH e imunoglobulina estimuladoras da tireoide, e a necessidade de submeter à PAAF todos os pacientes com hipertireoidismo associados a nódulo e cirurgia naqueles com alguma suspeita de malignidade. O caso apresentado mostra um microcarcinoma em uma paciente com diagnóstico pré-cirúrgico de BNT, considerado uma associação raríssima, porém, a revisão histopatológica confirmou a presença de microcarcinoma em BDT, cuja relação é bem mais conhecida. Referências: Araújo Filho, et al. Papillary Carcinoma in Graves Disease. Rev Col Bras Cir. 2001; 28(3); Kraimps JL, et al. Multicentre study of thyroid nodules in patients with Graves disease. Br J Surg. 2000; 87:1111-3; Zanella E, et al. Prevalence of thyroid cancer in hyperthyroid patients treated by surgery. World J Surg. 1998; 22:473-78; Razack MS, Lore Jr. JM, Lippes HA, et al. Total thyroidectomy for Graves disease. Head Neck. 1997;19:378-83.

PO. 074

A obesidade dobra o risco de desenvolvimento de câncer diferenciado da tiroide nas mulheres

Castaldi SA1, Marcello MA1, Cunha LL1, Assumpção LVM2, Ward LS1

1Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas da Unicamp; 2Ambulatório de Câncer da Tiroide, Disciplina de Endocrinologia, Faculdade de Ciências Médicas da Unicamp; Campinas, Brasil

introdução: Um aumento na incidência do câncer diferenciado da tiroide (CDT) tem sido consistentemente descrito nos últimos anos no Brasil e em todo o mundo. Embora a melhoria na detecção seja a grande responsável por esse aumento, outros fatores podem estar envolvidos. Idade, sexo, tabagismo, sedentarismo, perfil alimentar e de genes relacionados à interação com agressores ambientais são reconhecidos fatores de predisposição ao câncer. objetivo: O presente estudo investiga a associação entre o desenvolvimento do câncer de tiroide e o perfil alimentar e antropométrico. Método: Coletamos peso, estatura, e submetemos 141 pacientes com CDT (126 mulheres e 15 homens) cuidadosamente pareados com 126 indivíduos-controle (89 mulheres e 37 homens) para idade, fumo, sedentarismo, tabagismo e classe socioeconômica a um extenso questionário que incluía anamenese alimentar. Resultados: A avaliação do perfil alimentar mostrou que ambos, pacientes e controles, possuíam alimentação rica em gorduras e açúcares, com conteúdo insuficiente de fibras, frutas e vegetais e apresentaram insuficiente atividade física. O excesso de peso foi mais frequente nos pacientes com CDT (60,28%) do que no grupo controle (40,06%; p = 0,0046), dobrando o risco de desenvolvimento de CDT (OR = 2,066; IC95%: 1.266 a 3.371). O excesso de risco para CDT não foi observado no sexo masculino (p = 0,3498) em que a obesidade também é menos frequente (9,41%) que nas mulheres (90,54%), sugerindo que a obesidade possa estar relacionada com a maior incidência de CDT no sexo feminino. conclusão: A obesidade pode estar contribuindo para o marcante aumento de incidência de CDT, observado internacionalmente e também no Brasil, entre as mulheres.

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A presença de linfócitos infiltrantes está associada com características de agressividade tumoral, com o prognóstico e com a expressão de genes supressores tumorais nos carcinomas papilíferos da tiroide

Cunha LL1, Morari EC1, Guilhen ACT1, Bufalo NE1, Vassallo J2, Soares FA3, Ward LS1

1Laboratório de Genética Molecular do Câncer, Faculdade de Ciências Médicas da Unicamp; 2Departamento de Anatomia Patológica, Faculdade de Ciências Médicas da Unicamp; Campinas, Brasil

A presença de linfócitos infiltrantes tumorais (LIT) é uma evidência da resposta imunológica à neoplasia e poderia estar associada à evolução de carcinomas papilíferos da tiroide (CPT). O gene p53 ativa a expressão de MHCII e consequente apresentação antigênica, enquanto ATM desempenha papel essencial na resposta imune celular e humoral. Com o objetivo de avaliar a correlação de LIT com genes supressores tumorais e seu impacto na apresentação inicial e evolução do CPT, construímos um tissue MicroArray contendo 85 CPT. Havia 31 casos de estádio I; 18 estádio II; 36 estádio III/IV. Os pacientes foram submetidos a um mesmo protocolo de tratamento e seguidos por 25,01 ± 14,79 meses. Dados clínicos, achados intraoperatórios e anatomopatológicos, assim como de evolução, foram coletados de prontuários. As expressões imunoistoquímicas de ATM e p53 foram quantificadas e correlacionadas com o grau de infiltração linfocitária intratumoral classificado de acordo com a porcentagem da área tumoral ocupada por linfócitos. LIT foram mais frequentes em mulheres (p = 0,0371); tumores pequenos (p = 0,0341); menos invasivos (p = 0,0042); com menor desenvolvimento de metástases durante o seguimento (p = 0,0059) e maior tempo livre de doença (p = 0,0188). O grau de LIT se correlacionou com expressão de ATM (r = 0,2579). Os casos com ausência de LIT apresentaram menor expressão de p53 (p = 0,0079) e de ATM (p = 0,0122). A presença de LIT em tumores menos agressivos e de melhor evolução se associa com a expressão de genes supressores tumorais sugerindo uma interação genético-imunológica. A descrição de LIT pode ser de utilidade clínica na definição de grupos de risco/estadiamento do CPT.


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Anticuerpos a tiroglobulina: utilidad en seguimiento de carcinoma diferenciado de tiroides

Gauna A, Silva Croome M, Viale Fanny, Guillén CDivisión Endocrinología, Hospital Ramos Mejía; Buenos Aires, Argentina

La tiroglobulina sérica es el marcador más sensible en el seguimiento del cáncer diferenciado de tiroides (DTC). Su dosaje es interferido por los anticuerpos a tiroglobulina (TGAb), cuya prevalencia es alta en DTC. Hay estudios que avalan la utilidad de TGAb como marcador de evolución, pero su sensibilidad y especificidad son inciertas. objetivo: Evaluar tiempo de persistencia del TGAb y utilidad como marcador de enfermedad. Material y metodos: Se estudiaron 50 pacientes con DTC pos-tiroidectomía y radioablación, Estadíos: I (n = 39), II (n = 6) y III (n = 5), TGAb positivos, seguidos durante 105.3 + /-16.6 meses. Se consideró libre de enfermedad (LE): clínica, tiroglobulina, RCT, TAC/RMN, Eco de cuello negativos. Tiroglobulina dosada por IRMA, TGAb por ensayo directo. Estadística: tiempo expresado como mediana y rango, test t- student, sensibilidad, especificidad, agudezas de predicción positiva y negativa. Resultados: 47/50 pacientes negativizaron tiroglobulina en 10 meses (1-504) y 23/50 negativizaron TGAb en 26 meses (6-384) (p < 0.0005). A 3 años de seguimiento TGAb persistía positivo en 63% de 43 pacientes. De 23 pacientes que TGAb negativizó, 20 estaban LE. De 27 que TGAb se mantuvo positivo, 24 estaban LE. La Sensibilidad, Especificidad, Agudezas de Predicción Positiva y Negativa del TGAb fueron del 60, 45.5, 11.1, y 90.9% respectivamente. conclusiones: Sólo un tercio de los pacientes negativizó TGAb en 3 años, con un tiempo de negativización de 26 meses, significativamente mayor que para tiroglobulina. La persistencia de TGAb no fue un marcador útil de DTC, sí su negativización, que predijo la ausencia de enfermedad con agudeza del 90.9%.

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Prospective evaluation of percutaneous ethanol injections in benign thyroid nodules

Perez CLS, Bizeli R, Graf H, Carvalho GAEndocrinology Unit (SEMPR), Hospital de Clínicas da Universidade Federal do Paraná; Curitiba, Brazil

Background: Percutaneuos ethanol injection (PEI) is a therapeutic tool that has gained acceptance due to the accumulating evidences of its efficacy and safety for the treatment of symptomatic benign thyroid nodules. objective: To evaluate the efficacy and safety of PEI therapy in benign thyroid nodules. Methods: Twenty-five patients with benign solid nodules were evaluated. Serum thyrotropin (TSH), free thyroxine, thyroid scan (if suppressed TSH) and thyroid ultrasound (US) were performed. Sterile ethanol (99%) was injected under US guidance and the volume instilled corresponded to one third of the measured nodular volume. Complete response was defined as a volume reduction greater than 90%; partial response as a volume reduction between 50%-90% and no response as a volume reduction less than 50%. In autonomous nodules, the effectiveness was also assessed by the normalization of the thyroid hormone levels. Results: Solid nodules comprise 60% and complex cysts 40%; 20% were autonomous nodules. Two to six PEI sessions were performed per patient (average 3.4). After one year, 27.3% of all cases showed complete response (95.6% reduction); 50% partial response (76.8% reduction) and 22.7% showed no response. PEI induced autonomous nodules shrinkage, but only 40% showed normalization of thyroid hormone levels. The most common side effect was transient local pain observed in 89.5% of the patients. conclusion: These results suggest that PEI therapy is an effective and safe treatment in benign nodular thyroid disease. It causes nodular reduction, improving local symptoms, but may be less effective in autonomous nodules.

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Impact of retinoic acid on advanced thyroid carcinoma – 4 years of follow-up

Coelho SM1, Vaisman F1, Buescu A1, Corbo R2, Carvalho DP3, Vaisman M1

1Serviços de Endocrinologia; 2Medicina Nuclear; HUCFF; 3Laboratório de Fisiologia Endócrina, IBCCF; Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

Therapeutic options for de-differentiated thyroid carcinoma are limited. Recent studies demonstrated that retinoic acid (RA) can induce re-differentiation and tumor regression. Until today, there are limited studies analyzing the effectiveness of this drug. Therefore, we performed a prospective study to assess the value of RA in patients with advanced thyroid carcinoma and its real impact on tumor regression and cancer related death with a long-term follow-up. A total of 16 patients with inoperable and radioiodine non-responsive thyroid cancer were treated with RA and followed from 2002 to 2008. The mean age was 53 years old and patients had evidence of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST). The treatment was performed with 13-cis-RA (1.0 to 1.5 mg/kg/day) over 5 weeks followed by radioiodine therapy. The best responses were assessed 12 months after the last patient started treatment: objective partial response rate (defined by RECIST as 30% decrease in tumor measurements) was 25% (4 patients), stable disease rate was 25% (4 patients) and the progression disease rate (defined as increase in mass diameters or finding of new lesions) was 50%. In this group, 5 patients died (62.5%). Progression free survival rate (PFS) ranged from 72 to 12 months with median PFS of 26.5. Despite improved iodide uptake (62.5%), tumor shrinkage evaluated by RECIST criteria was less than expected (25%). Although a satisfactory response was seen in only 25%, recent studies with small molecule inhibitors showed similar PFS, suggesting that RA might be an option for de-differentiated thyroid cancer.


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Elevacion endogena de TSH como adyuvante al radioyodo en el tratamiento del bocio multinodular

Flores-Rebollar A1, Moreno-Castañeda L1, Ruiz-Juvera A2, López-Carrasco G2, Sepúlveda-Méndez J2, González-Treviño O2

1Dpto. de Medicina Interna; 2Medicina Nuclear; Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México, DF

El radioyodo (131I) es uno de los tratamientos utilizados para el bocio multinodular (BMN). En los últimos años se ha utilizado previo a la administración del 131I, TSHrh para incrementar su captación y con ello su efecto terapéutico. El uso de la TSHrh para este fin no esta totalmente aceptado. Se han reportado 2 casos (Albino C et al 2006 y Pitoia F et al 2008) de la elevación de TSH endógena como adyuvante en el tratamiento con 131I en BMN. Relato de un caso: Es referida a nuestro servicio para tratamiento una mujer de 60 años con BMN de varios años de evolución, en su evaluación inicial se encontró con una TSH de 0.02 mUI/L, T4 147.9 nmol/L, y una captación de 131I/24 hrs de 17%, con un volumen calculado por US de 77.22 ml, se realizó biopsia de 3 nódulos con resultado de benignidad. La enferma rechazó la realización de tiroidectomía, y se decidió iniciar una dosis baja de metimazol 15 mg/d, ajustándose este hasta elevar la TSH a 2.99 mUI/L (4 meses), y la captación de 131I/24hrs a 50%. Administrándose 25 mCi de 131I; a los 6 meses se iniciaron 50 mcg/d de levotiroxina por elevación de TSH a 2.64 mUI/L. Su última evaluación a los 12 meses post-radioyodo muestra un volumen tiroideo de 51.69 ml y TSH de 1.38 mUI/L. Conclusiones: Es posible que la elevación de TSH endógena pueda ser una estrategia útil, como adyuvante al radioyodo en el tratamiento del BMN.

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Escrutinio ultrasonografico tiroideo en una poblacion adulta en México

Flores-Rebollar A1, Navarro-Lara A1, Moreno-Castañeda L1, López-Carrasco G2, Ruiz-Juvera A2, Sepúlveda-Méndez J2, Gómez V2, Valles V3, González-Treviño O2

1Dpto. de Medicina Interna; 2Medicina Nuclear; 3Laboratorio de Endocrinología; Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”; México, DF

Los nódulos tiroideos son muy frecuentes en la población general, la estimación de su prevalencia es variable y depende del método de detección, usando ultrasonografía son detectados del 13%-50% en la población general. El objetivo del presente estudio fue evaluar la prevalencia de los nódulos tiroideos en individuos sanos sin enfermedad tiroidea conocida, de un área urbana con suficiente ingestión de yodo. sujetos y métodos: El grupo de estudio se compuso de 292 sujetos voluntarios sanos (129 hombres, 163 mujeres) reclutados del personal médico, paramédico y enfermería de nuestro hospital, se excluyeron enfermos tiroideos, con comorbilidad o tomando medicamentos que pudieran interferir con la función tiroidea. La edad promedio fue 28.47 ± 8.2 años (17-67 años, mediana 26 años). La ultrasonografía tiroidea se realizó con un equipo portátil GE Logic Pro 100 con un transductor lineal de 7.5 MHz, realizados por un mismo investigador (AFR). Resultados: El volumen promedio encontrado en el grupo total fue 10.05 ± 4.5 ml y fue mayor en los hombres 11.49 ± 4.4 ml que en mujeres 8.90 ± 4.32 ml. Los nódulos tiroideos fueron encontrado en 23/292 (7.87%), fue menor en hombres 5/124 (3.9%) y en mujeres 18/145 (11%). Se registró la ecogenicidad de la glándula según la escala de Zingrillo y 44.17% tuvieron ecogenicidad normal y 8.21% una hipoecogenicidad acentuada, el resto se distribuyen en las categorías de la escala. conclusiones: En nuestro grupo existe un porcentaje de nódulos menor a lo registrado, esto es explicado por un grupo predominantemente joven y posiblemente el aporte adecuado de yodo.

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Presunción de la incidencia de cáncer de tiroides en capital federal y el gran Buenos Aires (período 2003-2007) (thy-roid cáncer incidence in Buenos Aires)

Faure E, Soutelo MJ, Faraj G, Juvenal G, Lutfi RJServicio de Endocrinología, Complejo Medico (PFA) Churruca-Visca; Ciudad Autónoma de Buenos Aires, Argentina

introducción: La incidencia del carcinoma de tiroides (CT) en las últimas décadas está en aumento. En Argentina no existe un registro nacional de cáncer. En Buenos Aires se estimó una incidencia de 3,5 casos/año/100.000 habitantes en 1986*. objetivos: Determinar la incidencia de CT en la población de Capital Federal y Gran Buenos Aires en el período 2003-2007. Evaluar relación por género y frecuencia por histología. sujetos y métodos: Afiliados a obra social (n = 173.630 al 1/12/2007) residiendo más del 98% de ellos en Capital Federal y el Gran Buenos Aires). La patología endócrina se atiende únicamente en nuestro Servicio. Los Afiliados representan un 1,5% de la población de Capital Federal (2.776.138 habitantes) y el Gran Buenos Aires (8.684.437 habitantes) según el último censo 2001. Se analizó restropectivamente los nuevos casos de cáncer de tiroides entre 1/01/03 al 31/12/07 (60 meses). Resultados: Se detectaron 56 casos nuevos de cáncer de tiroides en 60 meses, la incidencia de CT fue de 6,45 casos/año/100.000 habitantes, la relación mujer/hombre fue 5,2:1. 87,5% (n = 49) fueron papilares, 10,71% (n = 6) foliculares; 1 caso (1,78%) anaplásico y no hubo ningún caso de carcinoma medular. conclusión: En nuestra población en 20 años hubo un incremento de la incidencia de CT cercano al doble. La frecuencia de carcinoma papilar aumentó en relación al folicular. Referen cia: *Niepomnizcze, et al. RAEM. 1986; 23 (2):49-50.


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Iodothyronine deiodinase type 3 expression in thyroid neoplasias

Zennig N, Wajner SM, Maia ALThyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul; Porto Alegre, Brazil

Background: The iodothyronine deiodinase type 3 (D3) is a selenoenzime that inactivates thyroid hormones. It is highly expressed in embryonic organs, but present in only a few postnatal tissues, such as central nervous system (CSN) and skin. Interestingly, recent data indicate that postnatal expression can be reactivated in tissues during pathological conditions as showed in critical illness and tumoral cell proliferation. D3 mRNA has been identified in some malignant cell lines and in a number of human tumors, including vascular tumors, CSN cancers and basal cell carcinomas. Few data is available about D3 levels or activity in tumoral thyroid tissues. The aim of this study was evaluate D3 mRNA levels and activity in normal and neoplastic thyroid tissues. Methods: Human thyroid samples were collected from thyroidectomies performed in our hospital between 2005 and 2008. Samples from normal thyroid tissue (n = 10), multinodular goiter (n = 8) and papillary thyroid carcinoma (n = 10) were analyzed. D3 mRNA expression was determined by semi-quantitative real time PCR and D3 activity by paper descendent chromatography measuring T2 released after incubation with [125I] T3. Results: D3 transcripts were present in all samples analyzed. No D3 activity levels were found in normal thyroid tissue. However, high levels of D3 activity were detected in multinodular goiter (0.23 ± 0.05 fmol/min. mg.protein) and papillary thyroid carcinomas (0.29 ± 0.04 fmol/min. mg.protein). conclusion: This study showed that D3 expression is reactivated in thyroid neoplastic tissues, suggesting that altered thyroid hormone metabolism might be implicated in benign and malignant thyroid neoplasias.

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Efecto de TGF-β1, TGF-β2 y TGF-β3 en células de cáncer folicular de tiroides humanas: rol del estrés oxidativo

Oglio R1, Thomasz L1, Juvenal GJ1, Pisarev MA 1-2

1Div. Bioquímica Nuclear, Dpto. Radiobiología, CNEA; 2Dpto. Bioquímica Humana, Facultad de Medicina, UBA; *ANPCyT; **CONICET; Córdoba, Argentina

introducción: Diversas observaciones sugieren que los efectos de TGF-β podrían ser mediados por el aumento de especies reactivas del oxígeno (EROs). Actualmente, no se conoce la participación del estrés oxidativo en la señalización inducida por el TGF-β en tiroides. objetivo: Estudiar la participación del estrés oxidativo en la disminución de la viabilidad celular inducida por el TGF-β, sobre una línea de carcinoma folicular (WRO). Metodología y resultados: La viabilidad celular se determinó por ensayo de MTT. Las células se trataron durante 72hs con dosis crecientes de TGF-β. Se observó una disminución del 20% con 0,5 ng/mL y entre el 30-40% con 5 ng/mL y 10 ng/mL (p < 0,01), independientemente de la isoforma utilizada (TGF-β1, TGF-β2 y TGF-β3). El aumento de EROs se detectó con la sonda fluorescente intracelular DCFH-DA. Se observó un incremento de EROs entre los 45 min y 180 min de incubación con 5 ng/mL de TGF-b (relación TGF-β vs. Control; 2,0 para TGF-β1 y TGF-β2 y 1,3 para TGF-β3). El efecto de TGF-b1 sobre el contenido intracelular de glutation (GSH) se determinó por el método Anderson (1985), obteniéndose una disminución del 40% a las 3hs y a las 24hs. Se estudió el efecto del Selenio sobre la inhibición de la viabilidad celular inducida por 5ng/mL de TGF-β1: 0,01µM de Selenio revierte el efecto inhibitorio de TGF-β1 en un 20% (p < 0,001). conclusión: Los resultados obtenidos sugieren que la disminución de la viabilidad celular de WRO mediada por TGF-β, podría tener a EROs como intermediarios.

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Tiroglobulina en nódulos tiroideos benignos: presencia de efecto hook

Viale F, Dios A, Lowenstein A, Glikman P, Reyes ADivisión Endocrinología, Hospital J. M. Ramos Mejía; Buenos Aires, Argentina

La determinación de tiroglobulina (TG) puede verse afectada por el efecto hook cuando este analito se encuentra excesivamente elevado. Esto ha sido demostrado en suero y tejido neoplásico maligno. Evaluar este efecto en nódulos tiroideos sólidos y quísticos (NTSQ) benignos es relevante siendo la TG utilizada para diferenciarlos de nódulos y quistes paratiroideos (NQPT). objetivos: 1) Determinar niveles de TG en NTSQ 2) Detectar efecto hook en NTSQ. Materiales: Fueron punzados 5 nódulos tiroideos -3 sólidos y 2 quísticos- cuyas citologías fueron bocios y quistes coloides, respectivamente. Metodología: Se determinó TG en líquido del lavado de aguja y en líquido del quiste. Se realizaron diluciones seriadas hasta encontrar 2 datos consecutivos en igual orden de magnitud. Se dosó TG por un ensayo inmunométrico quimioluminiscente (IQMA), fase sólida, un solo paso y anticuerpos antitiroglobulina (ATG) tambien por IQMA, (IMMULITE 2000). Se utilizaron como controles negativos adenopatías inespecíficas. Tg en NQPT 0,2-30 ng/ml. Resultados: Las TG (ng/ml) en las 5 muestras fueron, respectivamente: Sin dilución: 19.1/72.2/110/ > 300/ > 300; 1/10: 173/ > 300/ > 300/ > 300/ > 300; (1/10)2: > 300/ > 300/ > 300/ND/ND; (1/10)3: ND/ND/ > 300/53/55; (1/10)4: > 300/200/114/7.5/5.0; (1/10)5: 350/ND/ND/ND/ND, (1/10)6:50/5/1/ND/ND (ND = no dosado). En las primeras 3 muestras se detectó efecto hook. Todos los ATG fueron negativos. conclusiones: 1) Con esta metodología se detectó efecto hook en 3/5 nódulos tiroideos. 2) Por esta razón se propone su búsqueda en forma sistemática para la determinación de tiroglobulina en NTSG. 3) Las altas concentraciones de tiroglobulina halladas avalan su utilidad para la diferenciación entre nódulos/quistes tiroideos y paratiroideos.


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Insular thyroid carcinoma, a very aggressive – thyroid tumor

Miasaki FY1, Mesa Jr C1, Carvalho GA1, Ludwig VB2, Graf H1

1Endocrinology Service, Hospital de Clínicas da Universidade Federal do Paraná (SEMPR); 2Centro de Diagnóstico por Imagem (CETAC); Curitiba, Brazil

Background: Insular thyroid carcinoma (ITC) is situated morphologically and biologically in an intermediate position between the well-differentiated and undifferentiated tumors and presents a variable clinical course in a widely heterogeneous spectrum. objectives: To describe two patients with an aggressive form of ITC and evaluate the treatment efficacy. Patients: Patient 1. A 59 years female patient with ITC was submitted to total thyroidectomy (TT) and 131I, with negative whole body scan (WBS). Loco-regional recurrence occurred after 3 months, and a new surgery was done. A FDG-PET scan showed pulmonary and hepatic metastasis and chemotherapy was begun. After one year a new FDG-PET scan showed enhancement of pulmonary and hepatic metastasis and the patient died one year later. Patient 2. A 62 years old male patient with ITC was treated with TT and 131I. WBS was negative. He was submitted to three surgeries in the next 18 months for loco-regional recurrence, always with negative serum thyroglobulin (TG) levels. A FDG-PET scan six months later revealed numerous mediastinal and pulmonary metastasis, with esophageal compression. Surgery, radiotherapy and chemotherapy were tempted, but the patient died 4 years after the initial diagnosis. Results: Two patients with ITC, submitted to TT and 131I developed loco-regional recurrence 3 months after initial treatment. In spite of aggressive surgical, radiotherapy and chemotherapy treatment, the patients died shortly after ITC diagnosis. conclusion: ITC are aggressive thyroid carcinomas which respond very poorly to conventional treatment. Target-directed drugs should be tempted in ITC patients.

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Influencia del tamaño nodular en el resultado de la punción con aguja fina (PAF) en nódulos tiroideos menores de 5 cm

Díaz R, Wohllk NServicio de Endocrinología, Hospital del Salvador, Universidad de Chile, Campus Oriente; Santiago, Chile

introducción: Los nódulos tiroideos son una entidad clínica frecuente. Es sabido que a mayor tamaño nodular, existe mayor riesgo de malignidad. La punción con aguja fina (PAF) es muy importante en la evaluación de un nódulo, ayudando a seleccionar pacientes para cirugía. Algunos estudios han demostrado que el porcentaje de falsos negativos (FN) aumenta cuando el tamaño nodular es mayor, aunque los consensos de manejo de Nódulos no señalan claramente este punto. objetivos: El objetivo de este estudio es evaluar si el tamaño nodular influye en el resultado de la PAF, principalmente en nódulos tiroideos entre 1 y 5 cms de diámetro y determinar los tipos histológicos que con mayor frecuencia dan resultados FN. Material y métodos: Estudio de tipo descriptivo. Se revisaron las fichas clínicas de todos los pacientes operados por cáncer de tiroides en el Servicio de Endocrinología del Hospital del Salvador entre los años 1998-2008. De 319 pacientes, se seleccionaron 194 pacientes (202 nódulos) que tenían PAF guiada por ecografía. Se excluyeron los nódulos tiroideos menores de 1 cm y mayores de 5 cm de diámetro, como también los pacientes que presentaron microcarcinoma ( < 1 cm) en el estudio histológico, resultando un número final de 178 nódulos analizados. De las fichas se extrajo información respecto al tamaño nodular ecográfico, informe citológico de la PAF e informe histológico de la pieza operatoria. Resultados: de los 178 nódulos analizados por histología 148 (83,1%) correspondieron a carcinoma papilar. 18 (10.1%) folicular, 6 (3,4%) medular, 5 (2,8%) Hurthle y 1 (0,56%) indiferenciado. El estudio citológico por PAF fue: 108 (60,7%) malignas, 23 (12,9%) lesión folicular, 17 (9,55%) no concluyentes y 30 (16,85%) lesión benigna (punciones FN). Al analizar el tamaño nodular, hubo diferencia significativa entre los promedios de los grupos de punciones malignas o concordantes (25,87 mm) vs. benignas o no concordantes (28,8 mm) (T Test, p: 0,03). De los FN, el tipo de cáncer que arrojó el estudio histológico fue: papilar puro 33,3% (10), papilar variedad folicular 33,3% (10), folicular 20% (6) y 1 caso de cáncer de Hurthle, folicular insular, papilar oncocítico y papilar esclerosante respectivamente. conclusiones: Nuestro estudio demuestra que un mayor tamaño nodular aumenta el% de PAF falsos negativos en nódulos entre 1 y 5 cm sin poder establecer claramente un punto de corte.

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Puncion biopsia aspirativa con aguja fina (PBAF) en lesiones extratiroideas localizadas en cuello

Lowenstein A1, Santoro S1, Genoni V1, Olstein G2, Laudi R3, Reyes A1

1División Endocrinología; 2Servicio de Cirugía; 3Anatomía Patológica; Hospital JM Ramos Mejía; Buenos Aires, Argentina

La accesibilidad y el bajo costo de la PBAF consagraron a ésta como un método útil y rápido para diagnosticar lesiones de cuello extratiroideas y determinar si guardan relación con la tiroides. Materiales: Se obtuvieron los datos clínicos y diagnósticos finales citológicos e histológicos de 120 pacientes derivados al Consultorio de PBAF. Grupo 1: 102 con lesiones laterales y Grupo 2: 18 con lesiones mediales. Se consideró el antecedente de cáncer de tiroides (CT). Se utilizaron categorías citológícas habituales. Grupo 1: 1A) 41 pacientes con antecedentes CT: 23 (56%) citología maligna (carcinoma papilar: 22, poco diferenciado: 1), 15 (37%) citología benigna (adenitis reactiva: 8, granuloma: 5, lipoma: 1, adenoma pleomorfo: 1), 3 insatisfactorios. 1B) 61 pacientes sin antecedentes de CT: 31 citología maligna y sospechosa (22 CT: papilar: 17, medular: 3, folicular: 1, anaplásico: 1 y 9 carcinomas no tiroideos), 27 benigna (43,5%) (Adenitis: 12, quiste branquial; 4, granuloma: 3, lipoma: 3, neurinoma: 2, infeccioso: 2, quiste sebáceo: 1), 3 insatisfactorios. Grupo 2: 2A)17 sin antecedentes CT: 11 citología benigna (quiste tirogloso: 7, granuloma: 1, adenitis:1, otros: 2), 6 contenido quistico (quiste tirogloso: 5, carcinoma papilar: 1). 2B): 1 con antecedente de CT, citología sospechosa (carcinoma papilar) conclusiones 1) Las lesiones laterales con antecedentes de CT de cuello correspondieron en un 56% a persistencias/recurrencias de la enfermedad. En 61 lesiones sin antecedentes neoplásicos, la PBAF permitió diagnosticar 36% de CT y 10% de otras malignidades metastásicas. 2) La mayoría de las lesiones mediales corresponden a patología benigna (16/18).


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PO. 088

Papillary carcinoma in a thyroglossal duct cyst

Perez CLS1, Ramos HE1, Pedruzzi PAG2, Mesa Jr C1, Graf H1, Carvalho GA1

1Endocrinology Unit, Hospital de Clínicas da Universidade Federal do Paraná; 2Head and Neck Surgery Unit, Hospital Erasto Gaetner; Curitiba, Brazil

Background: The thyroglossal duct cyst (TDC) represents a common type of thyroid developmental abnormality. Malignancy is rarely encountered in TDCs (1%); usually papillary thyroid carcinoma or squamous carcinoma. The diagnosis of carcinoma in TDCs is based on the pathologic examination of the mass, but fine needle aspiration (FNA) cytology, ultrasound and computed tomography play a role in the differential diagnosis of malignancy. objectives: To describe a case of papillary carcinoma (PC) arising in a TDC. Methods: A 36 year-old woman presented to the endocrinologist with an asymptomatic anterior midline neck nodule. A cervical ultrasound showed a submentonian nodule, localized in the subcutaneous, hypoechogenic, regular margins, with calcifications and no vascularization, measuring 0.82 x 0.54 cm. FNA was performed. To investigate whether TDA exist in first degree relatives, thyroid ultrasonography were performed (n = 4). Results: The cytology suggested PC in ectopic thyroid tissue. The patient underwent total thyroidectomy and TDC resection. The histopathologic diagnosis showed PC in the TDC, with a tumor diameter of 8 mm, without evidence of carcinoma in the thyroid gland. None of relatives were affected for TDC but two had benign thyroid nodules. conclusion: Malignancy within a thyroglossal duct cyst is very rare but should be considered in the differential diagnosis of a midline neck mass. Therapy includes surgery, radioactive iodine and thyroid supression, as is the case for differentiated thyroid cancers. TDCs might present an autosomal dominant mode of inheritance with a low penetrance and first degrees relatives should be investigated.

PO. 089

Successful surgical resection of papillary thyroid cancer bone metastases preceded by arterial embolization

Perez CLS1, Wesley SRAG1, Bortoloni LGC1, Moura M2, Ludwig VB3, Carvalho GA1, Graf H1

1Endocrinology Unit (SEMPR), Hospital de Clínicas da Universidade Federal do Paraná; 2Orthopedics and Traumatology Unit, Hospital de Clínicas da Universidade Federal do Paraná; Curitiba, Brazil

Background: Papillary thyroid cancer (PTC) bone metastases generally present low iodine uptake and limited efficacy of 131I therapy. Alternative therapies include surgery, external radiotherapy, chemotherapy and embolization, among others. objective: To report a case of successful surgical resection of PTC bone metastases preceded by arterial embolization. Methods: A 44-year-old man with a tumoral mass in the right iliac bone was submitted to a biopsy that showed PTC metastases. Total thyroidectomy with lymph node dissection and 131I remnant ablation were performed. External bone radiotherapy followed by surgery was attempted but, due to local invasion, complete resection was not possible. Results: One year after PTC diagnosis he was admitted in our hospital. Cervical and abdominal ultrasound (US), chest computed tomography (CT) were normal. Pelvic CT showed an expansive lesion in the right hip with 12.5 x 7.0 x 8.5 cm and local invasion. Two sessions of arterial embolization were performed, with reduction of tumor size and vascularization, making right hemipelvectomy possible with complete tumor removal. Eight months after surgery, bone scan and pelvic CT were negative. One year after surgery, on T4, TG was 4.5 ng/ml. A FDG-PET scan showed no evidence of tumoral disease in the hip. conclusion: Arterial embolization preceding surgery was a safe and efficient alternative for the treatment of bone metastases of PTC in our patient.

PO. 090

Renal cysts as cause of false-positive in post-ablative dose whole bone scan (WBS) with I131 for differentiated thyroid carcinoma treatment

Santana CM, Souza PB, Lauand TGC, Santos AGA, Prado Jr LM, Pedrosa HCEndocrine Division, Hospital Regional de Taguatinga, Governo do Distrito Federal; Brasília, Brazil

Background: Many tissues express the sodium-iodine symporter and concentrate radioactive iodine. Unnecessary treatment occur due to false-positive findings. objective: To describe a WBS false-positive thyroid papillary carcinoma case. Material and method: Review of medical report and interview with the patient. Case report: CTQ, female, 28 years old, born in Brasília, FNAB compatible to papillary carcinoma and total thyroidectomy was indicated. No family thyroid history neither previous head/neck irradiation. The histopathology showed a moderately differentiated tall cell variant, non-enveloped, multicentric papillary carcinoma (largest fragment 08 mm). Two lymph nodes found to be affected (level II). Post-surgery WBS uptake was 1.7%, distant uptake absent. TSH 177.0 mcUI/L, thyroglobulin 31 ng/mL, anti-thyroglobulin < 20 UI/mL. An ablative 131I (150 mCi) was indicated. WBS post-dose revealed thyroid and right kidney uptake. Abdominal CT was performed showing simple renal cysts (Bosniak I) and residual granulomatous/infectious/inflammatory process. Further WBS demonstrated uptale restricted to thyroid. conclusions: As previous studies have shown similar WBS false-positive cases in kidney topography related to previous structural or damage (pyelo-calicial dilatation, large renal cysts) it is mandatory to perform a broad image investigation and even biopsy might be necessary in these unusual findings. References: 1. Zanotti-Fregonara P et al, Update on the diagnosis and therapy of distant metastases of differentiated thyroid carcinoma. References: Minerva Endocrinol. 2008; 16; Salvatori M, et al. Unusual false-positive radiodine whole-body scans in patients with differentiated thyroid carcinoma. Clin Nucl Med. 1997;22 (6):380-4. Department of Nuclear Medicine, Catholic University of the Sacred Heart, Italy.

PO. 091


S202

Frecuencia del cancer de tiroides en patología quirúrgica tiroidea

Falcon-de-Legal E1, Ramos M2

1Servicio de Endocrinología y Metabología; 2Servicio de Anatomía Patológica; Hospital Central, Instituto de Previsión Social; Asunción, Paraguay

objetivo: El presente trabajo tiene como objetivo medir la frecuencia de los diferentes tipos histológicos de carcinoma de tiroides de muestras retiradas como resultados de cirugías de tiroides, en pacientes del Hospital Central del Instituto de Previsión Social (HC-IPS), Asunción, Paraguay; en el periodo comprendido de Enero de 2000 a Diciembre de 2004. Población y muestra: Todas las piezas quirúrgicas de patologías tiroideas que fueron estudiadas y registradas en el Servicio de Patología y Diagnóstico del HC-IPS. Del total de 281 casos estudiados. Los carcinomas representaron en total 34 casos, correspondiendo a un total de 12,1% de los casos, con preponderancia femenina. Los carcinomas mas frecuentes fueron los diferenciados (94,12%), fundamentalmente los carcinomas papilar con 29 casos (85,3%) con franja etaria entre 40 y 50 años de edad y la edad media de 43,9 (± 14) años. A continuación, 3 casos de carcinoma folicular (8,82%) predominando en las mujeres con una media de edad de 55,33 (± 24,41) años. Finalmente, el carcinoma anaplásico, con 2 casos (6,9%) exclusivamente femeninos en la franja etaria de 70 a 80 años, con una media de edad de 74,5 (± 6,36) años. conclusión: El carcinoma papilar sigue siendo el más frecuente entre los ca diferenciados de tiroides en población estudiada, concordando lo descrito en la literatura científica.

PO. 092

Carcinoma papilar de tiroides familiar – nuestra experiencia

Faure E, Schwarsztein D, Novelli JL, Cale J, de Candia L, Juvenal G, Lutfi RServicio de Endocrinología Complejo Médico Churruca Visca Buenos Aires Centro de Tiroides Rosario; Buenos Aires, Argentina

introducción: La forma familiar del carcinoma papilar de tiroides, ha sido documentada recientemente. Se considera una entidad con mayor agresividad que la forma esporádica. El objetivo de este trabajo fue evaluar las características clínicas e histológicas del carcinoma papilar familiar de tiroides según nuestra experiencia. Materiales y métodos: Se evaluó retrospectivamente los datos de tres bases de Historia Clínicas: Centro de tiroides “José Luís Novelli” y Dr. Diego Schwarzstein, ambos de la ciudad de Rosario, y Hospital Churruca-Visca de Buenos Aires, Argentina. Encontrándose 11 pacientes de 5 familias con antecedentes de carcinoma papilar de tiroides documentados con datos de diagnóstico, presentación, histología, tratamiento, evolución y seguimiento. Edad promedio 38,36 años (rango 18-52). Todos los pacientes de sexo femenino. Resultados: El diagnóstico en la mayoría de los casos fue por el hallazgo en el examen físico. En 3 familias, las afectadas fueron madre e hija y en dos, hermanas. Se efectuó tiroidectomía total a todos los pacientes y a 10 vaciamiento ganglionar. Hallazgos histológicos: tamaño promedio: 15,2 mm (rango 7-50 mm). 6 carcinoma papilar variedad usual, 3 variedad folicular, 1 esclerosante y 1 esclerosante difuso. Invasión vascular: 0/11. Extensión extratiroidea: 5/11. 2/11 bilaterales y multifocales. 7/11 presentaron metástasis ganglionar y 1 extensión extracapsular ganglionar. En 2 pacientes se observó recurrencia y en 1 persistencia de enfermedad locoregional. No se registraron pacientes con metástasis a distancia. conclusión: Encontramos en nuestra población de carcinoma familiar no medular un comportamiento más agresivo en comparación con la forma esporádica.

PO. 093

Marcación prequirúrgica con arpón metálico en metástasis cervicales de carcinoma papilar tiroideo

Faure E1, Lambertini R3, Farías P3, Figari M4, Villar A2, Simkin D1Servicio de Endocrinología; 2Servicio de Cirugía, Complejo Médico PFA Churruca-Visca; 3Servicio de Diagnóstico por Imágenes; 4Servicio de Cirugía, Hospital Italiano de Buenos Aires; Buenos Aires, Argentina

introducción: La ecografía en el seguimiento del cáncer tiroideo permitido la detección de metástasis en ganglios pequeños o no palpables. Su resección a veces es dificultosa debido a sus dimensiones, a la distorsión anatómica por cirugías previas o a su localización. La marcación del sitio de la lesión puede minimizar estos problemas. objetivo: Demostrar la utilidad de la marcación con arpón metálico en metástasis ganglionares cervicales de carcinoma papilar tiroideo como guía para una resección quirúrgica efectiva. Material y métodos: Se marcaron con arpón 21 ganglios en 16 pacientes con antecedentes de carcinoma papilar tiroideo, 15/16 con tiroidectomía, 12/16 con vaciamiento recurrencial, 6/16 lateral y 1/16 sin cirugía aún. Todos los ganglios estaban biopsiados, 17 metástasis y 4 negativos (neuroma de amputación n = 2, granuloma n = 1 y ganglio reactivo n = 1). La marcación se efectuó dentro de las 4 y 24 hs previas a la cirugía, bajo guía ecográfica y anestesia local. Se utilizó arpón metálico Inter-V con introductor de 20 Gauge. Resultados: Todas las lesiones fueron resecadas (niveles III y IV n = 13, VII n = 6 y V n = 2) y el diagnóstico final coincidió en el 100% con la citología pre-quirúrgica. 20/21 arpones fueron identificados anclados dentro de la lesión resecada. 1/21 arpón se movilizó quedando anclado en la vena yugular y la lesión fue identificada por contiguidad. conclusión: La marcación con arpón metálico es un procedimiento seguro y eficaz. Permite al cirujano localizar rápidamente lesiones no palpables en cuellos sometidos previamente a cirugía, o bien asegura su resección durante un vaciamiento cervical.


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Análise da prevalência de carcinoma papilífero familiar de tireoide

Gomes EMS, Buescu A, Vaisman MServiço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

introdução: Estima-se uma origem familiar em 3,5%-6,2% dos pacientes com carcinoma não medular familiar de tireoide. objetivo: Avaliar a prevalência de carcinoma papilífero de tireoide (CPT) entre os familiares de primeiro grau de portadores desta patologia que estão em acompanhamento clínico regular no Hospital Universitário Clementino Fraga Filho, no Estado do Rio de Janeiro (HUCFF-RJ). Métodos: Realizamos um estudo de corte transversal analisando 143 familiares de primeiro grau de 52 portadores de CPT (casos índices), sendo a média de 2,75 familiares por caso índice. Consideramos carcinoma papilífero familiar de tireoide a presença de ao menos dois casos entre parentes de primeiro grau. Os pacientes que apresentavam ao menos três características ultrassonográficas de malignidade em nódulos menores que 1 cm e os > 1cm foram submetidos a PAAF e avaliação citológica. Em caso de diagnóstico de malignidade, os pacientes foram encaminhados para cirurgia. Também foram utilizados para análise os dados histopatológicos de indivíduos previamente tireoidectomizados. Resultados: Dos 143 familiares de primeiro grau de portadores de CPT, 11 (7,7%) também possuíam esta patologia. Entre as 52 famílias estudadas, identificamos 10 com carcinoma papilífero familiar de tireoide (CPFT), sendo que em uma delas existiam três membros acometidos pela doença. conclusão: A prevalência de CPFT encontrada foi de 7,7% entre os pacientes em acompanhamento clínico regular no HUCFF-RJ.

PO. 095

Anormalidades morfológicas da tireoide em familiares de primeiro grau de portadores de carcinoma papilífero de tireoide

Gomes EMS, Buescu A, Vaisman MServiço de Endocrinologia, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro; Rio de Janeiro, Brasil

introdução: Estima-se um aumento de até cinco vezes no risco de desenvolvimento de carcinoma papilífero familiar de tireoide (CPFT) em parentes de primeiro grau de portadores de carcinoma papilífero de tireoide (CPT). objetivos: Identificar as alterações ultrassonográficas em familiares de primeiro grau de portadores de CPT e avaliar o uso deste método para triagem de casos de CPFT. Métodos: Realizamos um estudo de corte transversal avaliando a estrutura da tireoide através de ultrassonografia em 125 familiares de primeiro grau de 52 portadores de CPT (casos índices), sendo a média de 2,4 familiares por caso índice. Consideramos CPFT a presença de ao menos dois casos entre parentes de primeiro grau. Resultados: Dos 125 pacientes que fizeram ultrassonografia de tireoide, os exames estavam alterados em 68 (54,4%) indivíduos. Identificamos uma textura glândular heterogênea em 6 (8,8%), cistos simples em 13 (19,11%) e a presença de doença nodular em 49 (39,2%) pacientes. Destes últimos, 24 (19,2%) apresentavam nódulo único e 25 (20%) bócio multinodular (BMN). Foram encontrados, ao final do estudo, 11 casos de CPFT: 7 eram previamente tireoidectomizados e os outros 4 apresentavam BMN (100%; p = 0,001). Entre os que possuíam BMN à USG, 16% tinham CPFT (p = 0,001). conclusão: BMN foi visto em todos os pacientes com CPFT submetidos à ultrassonografia de tireoide. Apesar pequeno número de pacientes, concordamos com alguns autores que sugerem que a presença dessa alteração é mais comum neste subgrupo de pacientes e que a ultrassonografia deve ser o método de triagem para CPFT.

PO. 096

Avaliação da eficácia do tratamento com iodeto-131I em pacientes com carcinoma diferenciado de tireoide

Martins Filho R, Matos PS, Lima MCL, Santos AO, Ramos CD, Ward L, Assumpção LVM, Etchebehere ECSCUnicamp; Campinas, Brasil

Pacientes com câncer diferenciado de tireoide geralmente têm um bom prognóstico. Entretanto, até 15% dos casos evoluem com recorrência e não responde à terapia com iodeto-131I (RIT). Para avaliar a efetividade da RIT, foram analisados 151 pacientes com carcinoma diferenciado da tireoide (126 femininos, 25 masculinos, 44,7 ± 14,4 anos). A maioria (82,6%) apresentava carcinoma papilífero (CP), incluindo as variantes de células altas (12 pacientes); variante esclerosante (1 paciente); células colunares (1 paciente). Os demais 26 casos apresentavam carcinoma folicular (CF), incluindo 4 variantes de células de Hurthle e 4 francamente invasores. Todos os pacientes foram submetidos à tireoidectomia total seguida de pesquisa de corpo inteiro com iodeto-131I e dosagens séricas periódicas de tireoglobulina por 64 ± 51 meses (mínimo de 13 e máximo de 252 meses). Foi realizado um total de 256 RITs com dose terapêutica de 100 até 1200 mCi (285 ± 194,6 mCi). A análise evolutiva identificou 10 pacientes (6,6%) ainda com evidência de doença, sendo 4 CF (2 com células de Hurthle) e os outros 6 CP (2 com células altas e um esclerosante nodular). A dose cumulativa máxima administrada foi de 880 mCi neste subgrupo. Os demais 142 pacientes que se encontram livres de doença receberam dose cumulativa máxima de 1.030, maior que aquela recebida pelos pacientes com má evolução. Entre estes últimos havia mais CF (40% vs. 14%; p = 0,02) e CP de formas variantes (30% vs. 11%; p = 0,02). Demonstramos que a eficácia da RIT não se correlacionou com a dose total máxima, mas sim com a diferenciação celular.


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PO. 097

Concomitância de carcinoma papilífero e linfoma MALT de tireoide

Melo GM, Sguillar DA, Baptistella LC, Souza RASClínica e Cirurgia de Cabeça e Pescoço do Hospital da Beneficência Portuguesa de São Paulo; São Paulo, Brasil

introdução: O carcinoma papilífero da tireoide (CPT) é o tumor tireoidiano mais frequente, respondendo por cerca de 80% dos casos no EUA (1), acomete mais mulheres (3:1) (2) e ocorrem entre a 3ª e 4ª décadas (3). Os linfomas primários de tireoide são incomuns, representando 0,6% a 5% das neoplasias malignas (4), acometendo mulheres na 6ª década e relacionando-se com a tireoidite de Hashimoto (5). A concomitância é rara, porém descrita ocasionalmente na literatura (4,6). objetivo: Descrever um caso de paciente submetido à tireoidectomia total com exame anatomopatológico evidenciando carcinoma papilífero multicêntrico, linfoma MALT concomitante e tireoidite de Hashimoto. Métodos: Paciente masculino, 61 anos, assintomático, com USG cervical: glândula tireoide heterogênea, multinodular, vol.: 54 cm3, sem linfonodomegalias e antitireoglobulina: 119 IU/mL. Antecedente familiar de carcinoma de tireoide. Resultados: Realizada tireoidectomia total com AP: CPT multicêntrico, variante clássica, margens livres, sem invasão angiolinfática, tireoidite de Hashimoto e linfoma MALT concomitante, cercado de tecido normal, com IMH: CD 20, CD 43, CD 79, AE1/AE3 positivos. Pós-operatório sem anormalidades. Iniciados terapia hormonal supressiva e estadiamento: PET-CT e Cintilografia-MIBI: sem lesões ativas. Realizou-se radioiodoterapia (RIT): 150 mCie e PCI: sem lesões residuais. Não foi indicado tratamento com radioterapia. Atualmente em terapia supressiva com TSH: 0,64; T4L: 1,7 e TGB: indetectável, sem recidivas. conclusões: Os linfomas de tiroide devem fazer parte do diagnóstico diferencial na presença de tireoidite linfocitária. Os pacientes com a concomitância do linfoma MALT e CPT devem ser criteriosamente avaliados, pois o tratamento inicial deve priorizar o tumor de maior risco de disseminação.

PO. 098

Diagnóstico de câncer de tireoide: concordância entre punção aspirativa com agulha fina e exame anatomopa-tológico

Kruschewsky LS, Azi NM, Lessa B, Tricolli R, Caracas N, Santos RRAHospital Aristides Maltez; Faculdade de Medicina FTC; Salvador, BA, Brasil

introdução: A tireoide representa o principal sítio endócrino de câncer. O advento da punção aspirativa com agulha fina (PAAF) guiada por ultrassom (USG) tem facilitado o diagnóstico e a descrição dos tipos histológicos dessa patologia. Entretanto, a acurácia diagnóstica da PAAF é variável, dependendo de diversos fatores. objetivo: Calcular as sensibilidade e especificidade da PAAF guiada por USG de nódulos de tireoide em pacientes acompanhados no Hospital Aristides Maltez (HAM), comparando, então, sua efetividade, com aquela do exame anatomopatológico, realizado após o tratamento cirúrgico. Métodos: Corte retrospectivo. Selecionados 97 prontuários dentre 120 analisados e feita a coleta de dados relativos ao resultado da PAAF e do exame histológico realizado após o tratamento para câncer de tireoide, no HAM, entre 2000 e 2007. Resultados: Dos 97 pacientes selecionados, 13 (13,4%) eram do sexo masculino e 84 (86,6%) do sexo feminino, sendo a média de idade de 44,18 ± 13,07 anos. O diagnóstico citológico mostrou-se negativo para malignidade em 16 casos, positivo em 72, suspeito em 8 casos e inconclusivo em 1. O exame anatomopatológico revelou malignidade em todos os casos. A sensibilidade da PAAF, quando esta se mostrou conclusiva, foi de 81,81%. conclusão: A PAAF guiada por USG é método sensível para o diagnóstico de câncer de tireoide, excetuando-se situações clínicas específicas, devendo fazer parte dos dados clínicos para decisão cirúrgica sempre.

PO. 099

Thyroglobulin detection in fine- needle aspirates of cervical lymph nodes in non-thyroidectomized patients

Bergoglio L1, Mahler G1, Cuvertino E3, Geres A2, Romero N4, Mereshian P2, Iturbe B5

1Laboratorio de Endocrinología; 2Postgrado de Endocrinología; Hosp. de Clínicas Univ. de Córdoba; 3Centro Privado de Ecografía; 4; 5Laboratorios Privados de Anat. Patológica; Córdoba, Argentina

Background: The detection of thyroglobulin (Tg) in the washout of FNA (WFNATg) is used to identify lymph nodes (LNs) metastases from DTC as an adjunct to cytology. Before surgery, this is relevant since it usually requires neck dissection in addition to total thyroidectomy. However, low levels of Tg by some methods in non-metastatic LNs lead to define an appropriate cutoff. objectives: a)To evaluate the performance of WFNATg for detecting LNs metastases in patients with thyroid gland in situ; b) To establish a WFNATg cutoff using DPC/Siemens chemiluminescent immunoassay. Methods: Ultrasound guided FNA was performed in 18 patients (20 LNs), 15 females and 3 males, mean ages ± SD: 40 ± 20 years, with suspicious thyroid nodules and neck LNs enlargement, for cytologyc, WFNATg and WFNATgAb analyses. Results: Comparing FNA cytology with WFNATg: metastases of PTC: 12 LNs (60.0%)/Tg range:104-65700 ng/ml, mean ± SD: 15465 ± 18533; TgAb was positive in one metastatic LN with no diagnostic consequence; reactive: 8 LNs (40.0%)/Tg range 1-30 ng/ml, mean ± SD: 5.7 ± 10.2 ng/ml; because of the small size of the serie, the highest Tg concentration in LNs with negative citology: 30 ng/ml (negative histology) was selected as cutoff instead of mean ± 2SD. conclusion: – WFNATg was in agreement with cytologyc findings. – A WFNATg value above of 30 ng/ml was specific of thyroid tissue.- Positive WFNATg in LNs of patients awaiting thyroidectomy is a useful tool to prompt neck dissection in addition to total thyroidectomy.


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Retrospective evaluation of pacients with a differentiated thyroid cancer (DTC) observed in the ambulatory of endocri-nology service of Taguatinga regional hospital (HRT)

Sousa PB, Santana CM, Pedrosa HC, Faria CP, Azevedo GFM, Lauand TGCEndocrine Division, Hospital Regional de Taguatinga, Governo do Distrito Federal; Brasília, Brazil

Background: Cancer affects 5% to 10% of the thyroid nodules. objective: To present the experience concerning the diagnosis, treatment and follow up of the DTC. Materials and method: Retrospective analysis of patients with DTC who had appointments at HRT, review of medical files and patients interview. Results: 31 patients aging 25-65 years were included. The period of observation varied from 06 to 22 years. We found 84% pappilary and 16% follicular carcinomas. Four patients (13%) had cytological diagnosis to FNAB of adenomatoid goiter and four patients (13%) showed distant metastasis. The 2006 TNM classification (European consent for management of patients with DTC) were applied: 2 cases of very low-risk, 9 low-risk, 12 high-risk. The turn-over rate was greater for males (40%) in comparison to females (30%). Relapse was verified among older patients (over 45 years old). Only 6.8% had positive levels of Anti-TG. conclusion: We currently have 30 patients under regular observation. From these ones, 30% showed tumoral recidivism. Some data complied with the literature such as age, gender and distant metastasis. FNAB might not have disagreement to histological diagnosis but possible, missing cancer diagnosis in the contra-lateral nodule. The low positive levels of Anti-TG is probably related to poor efficacy of laboratorial exams. Therefore there is a need to circumvent the lack of parameters found in the sample by means of setting up a proper data collection. Reference: Maia, et cols. Nódulos de tireoide e câncer diferenciado de tireoide: consenso brasileiro. vol.51, nº5 Sao Paulo, Julho/2007.

PO. 101

Differentiated thyroid carcinoma: alteration in size pattern along more than 30 years of follow-up

Assumpção LVM, Denardi FC, Moura-Neto A, Melo TGEndocrinology Division of Internal Medicine Department, State University of Campinas; Campinas, Brazil

Background: We observed a great advance and increasing availability of thyroid evaluation methods. Due to this, smaller differentiated thyroid carcinomas (DTC) have been diagnosed and extensive tumors are rare nowadays. objective: Evaluate DTC nodules size between the last three decades among patients from our Endocrinology Division. Methods: Retrospective analysis of 449 patients who were followed from 1973 until 2007 at Endocrinology Division. The tumors were grouped by decades and separated according to their size. Results: We evaluated 355 patients with papillary thyroid carcinoma and 94 patients with follicular thyroid carcinoma. Among patients with PTC, there was a increase in microcarcinoma (tumor size ≤ 1 cm) proportion, from 9% in 1976-1985 to 27,8% in 1996-2005 and decreased to 19,8% in 2006-2007. On the other hand, tumors greater than 4 cm has decreased in the proportion from 27,3% in 1976-1985 to 16% in 1996-2005 and 11,8% in 2006-2007. Extensive PTC, above 10 cm, were rare, only between 1996 and 2000, in 2,8% of cases. Analysis of FTC patients demonstrated the greater proportions of cases along the whole period were above 4 cm. We have observed an increase in the proportion of small size tumors (1,1-2 cm), from 6,2% in 1986 to 12% in 1996-2005 and 16,6% in 2006-2007. conclusions: We confirm a trend in increasing diagnosis of smaller PTC and a reduction in PTC greater than 4 cm in the last three decades. Among FTC, tumors greater then 4 cm are still the majority of cases, although a slow increase in smaller size are being seen.

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Evaluation of bone mineral density in patients with TSH suppressive therapy due to differentiated thyroid carcinoma

Melo TG, Denardi FC, Moura-Neto A, Assumpção LVMEndocrinology Division, Internal Medicine Department, State University of Campinas; Campinas, Brazil

Background: Patients with differentiated thyroid cancer (DTC) are treated with long-term thyrotropin (TSH)- suppressive thyroxine replacement therapy, resulting a state of subclinical hyperthyroidism. This may have some adverse effects on bone. Overt hyperthyroidism is clearly associated with a higher incidence of osteoporosis. The relationship between subclinical hyperthyroidism and osteoporosis in not very clear, some studies evidence a relationship and others do not. objective: Study the bone mineral density (BMD) state in a cohort of patients treated with long-term TSH suppressive therapy due to DTC. Methodology: Evaluation of BMD (using DXA equipment) of patients with DTC followed at our Endocrinology Division since 1973. Patients were submitted to BMD evaluation due to post-menopausal state, advanced age (men) or presence of other risk factors for low bone density. Results: Three men and sixty-three women had their BMD evaluated. Men aged 45-81 and women aged 32 to 85 years-old. Duration of TSH-suppressive therapy before BMD evaluation ranged from 1 to 34 years. Only three patients had presented transitory hyperparathyroidism. Majority of patients were followed with TSH levels < 0,1 mUI/mL. No men had osteoporosis, 2 presented normal BMD and one showed osteopenia. Among post-menopausal women, 36,5% evidenced osteoporosis, 28,5% evidenced osteopenia and 34,9% had a normal DMO. conclusions: This prevalence of osteoporosis is not higher than what is described for general population, according to the National Osteoporosis Foundation (NOF-USA). NOF states that 40%-72% of post-menopausal women has osteopenia or osteoporosis.


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Carcinoma papilar de tiroides y enfermedad de Graves: presentacion de un caso

Juarez XEDepartamento de Medicina Interna, Hospital Nacional San Juan de Dios de San Miguel; El Salvador

introducción: Las enfermedades autoinmunes tiroideas son frecuentemente asociadas con carcinomas diferenciados de tiroides. El rol del fenómeno autoinmune en el origen y curso clínico de este tipo de cáncer es todavía controversial. Algunos estudios han demostrado rangos de incidencia tan bajos como 1% y tan altos como 9%. Un estudio multicéntrico británico demostró una incidencia de 3.8% y en una clasificación y caracterización de nódulos en Enfermedad de Graves realizada en 1998 se demostró que el 10% de todos los nódulos presentaban cáncer. En algunos estudios se ha encontrado que los carcinomas diferenciados de tiroides también pueden ocurrir en pacientes con Enfermedad de Graves sin nódulos y que la ausencia de nódulos en la ultrasonografía no reduce el riesgo de malignidad. objetivo: Relatar un caso de Carcinoma Papilar de Tiroides en una paciente con Enfermedad de Graves. Presentación del caso: Se trata de una joven de 26 años de edad, conocida en nuestro servicio de endocrinología por Enfermedad de Graves, tratada con antitiroideos y beta bloqueadores. Se le realizó Ultrasonido Tiroideo, presentando dos nódulos en el lóbulo tiroideo derecho y uno en el izquierdo, todos hipoecogénicos con microcalcificaciones. El gammagrama tiroideo con yodo 131 mostró captación del 78.6% predominantemente en el lóbulo derecho de la tiroides. Se realizo biopsia por aspiracion con aguja fina (BAAF) en dos ocasiones mostrando células foliculares de varios tamaños con atipias en ambos lóbulos, sugerente de carcinoma papilar de tiroides. Se programó tiroidectomía total presentando al examen histopatológico de la muestra carcinoma papilar de tiroides del lóbulo derecho, izquierdo e istmo con invasión capsular. Se le dió ablación con yodo 131 post-quirúrgica. conclusion: La evolución de la paciente a largo plazo ha sido satisfactoria encontrandose la misma actualmente con supresión hormonal con 0.15 mg de levotiroxina sódica y sin evidencia de enfermedad locorregional.

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Análisis con cinco escalas de estadificacion pronóstica de los pacientes con cancer diferenciado de tiroides del hos-pital de especialidades del Centro Medico “La Raza”

Sosa CA, Mora HS, Alamilla LL, Velázquez CFJ, Galindo RMEInstituto Mexicano del Seguro Social Unidad Médica de Alta Especialidad CMN “La Raza”; Ciudad de Mexico, Mexico

introducción: Existen diversas escalas pronósticas de clasificación en pacientes con cáncer diferenciado de tiroides (CDT) que sirven para estimar la sobrevida, establecer el plan de manejo y seguimiento. objetivo: Analizar el estadio de los pacientes con CDT del HECMNR aplicando cinco escalas pronósticas. Métodos: Se realizó una revisión de la base de datos de pacientes con diagnóstico histopatológico de CDT. Se utilizaron las escalas TNMp 5ª, EORTC, Universidad de Chicago, Noguchi y AMES. Se aplicó T de Student y R de Pearson (bilateral p < 0.05). Resultados: Se incluyeron 510 pacientes; edad promedio al diagnóstico de 44 ± 13 años (7-88); 90% fueron del género femenino y 10% del masculino; el carcinoma papilar representó el 96.7% de los casos y el folicular 3.3%. Tiempo de seguimiento promedio 6 ± 5 años (0-27). La invasión a la cápsula en el 58.6%, metástasis a ganglios linfáticos del cuello 30.8%. Se consideraron de bajo riesgo (n = 510) para TNMp 5ª el 69.59%, alto riesgo 30.41%; EORTC 82.93% y 17.07%; Universidad de Chicago 40.77% y 59.23% respectivamente; para Noguchi (n = 309) 88.34% bajo riesgo, 7.44% riesgo intermedio y 4.22% alto riesgo; AMES (n = 309) 45.49% y 54.51% de bajo y alto riesgo, respectivamente. conclusiones: El género masculino es diagnosticado en estadios más avanzados. Se encontró correlación negativa entre la edad y tiempo de sobrevida (p < 0.04). La clasificación TNMp 5ª fue la única estadísticamente significativa para la sobrevida de los pacientes (R de Pearson < 0.05).

PO. 105

Cáncer diferenciado de tiroides (CDT): eficiencia de las distintas metodologías diagnosticas en adenopatias cervi-cales sospechosas

Puscar A, Orlandi A, Sequera A, Frascaroli G, Fideleff HHospital Alvarez- Aranguren 2701. CABA; Buenos Aires, Argentina

La PAAF bajo ecografía es el método más confiable para examinar nódulos cervicales en el seguimiento del CDT con sospecha de recurrencia (R). La Tiroglobulina (Tg) en líquido de punción (Tg-LP) contribuyo a mejorar su diagnóstico. objetivo: Evaluar la relación entre valores de Tg- LP con ecografía y citología sospechosas de R. Material y metodos: Estudiamos 24 pacientes con 45 adenopatías cervicales durante su evolución. Se realizó simultáneamente PAAF bajo ecografía, citología, dosaje de Tg-LP, Tg sérica (IFMA) y aTG (IQMA). Calculamos sensibilidad (S) y especificidad (E) considerando: verdaderos positivos V (+): para Tg-LP: valores mayores a Tg sérica; para ecografía: cambios sospechosos y en citología: compatibles con R. Resultados: 20 ganglios mostraron ecografía sospechosa (13 tenían Tg-Lp > 20 ng/ml). Citología compatible con R en 10, y Tg-LP elevada en 14 (un paciente con Tg = 4,4 ng/ml presentó ecografía normal). Confirmamos R histológicamente en 13 ganglios operados (11 pacientes). Dos ecografías sospechosas con Tg-LP no dosables correspondieron a patologías extra tiroideas. Ninguna adenopatía con ecografía no sospechosa evidenció R. Los métodos evaluados mostraron: en Tg-LP: S 100% y E 97%; ecografía: S 100% y E 81% y citología: S 35% y E 100%. conclusiones: Tg-LP fue el método más útil para el diagnóstico de R en adenopatías cervicales, comparado con las otras metodologías. Si bien la citología presentó la mayor especificidad, interpretamos que su baja sensibilidad estaría asociada al escaso material proveniente de pequeñas lesiones. Esto permitiría jerarquizar el valor de la ecografía en la evaluación de estos pacientes.


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Avaliação dos pacientes com carcinoma de tireoide acompanhados no Ambulatório de Endocrinologia do Hospital das Clínicas da Universidade Federal de Goiás no período de agosto de 1995 a outubro de 2008

Melo APM, Albieri CD, Bueno FN, Fernandes ARGC, Jatene EM, Paula SLFM, Antunes DE, Viggiano DPPOServiço de Endocrinologia do Hospital das Clínicas da Universidade Federal de Goiás; Goiânia, Brasil

introdução: Os carcinomas de tireoide correspondem a 1% de todos os cânceres, sendo a neoplasia maligna endócrina mais prevalente. A incidência no Brasil é de 0.2-11.6/100.000 habitantes e é mais prevalente em mulheres. objetivos: Analisar dados demográficos, tipos histológicos e estratificação de risco, e avaliar opções terapêuticas utilizadas e efetividade do tratamento no carcinoma de tireoide. Metodologia: Estudo descritivo de 34 pacientes com carcinoma de tireoide atendidos no Ambulatório de Endocrinologia do HC/FM-UFG de agosto/1995 a outubro/2008. Resultados: A idade média do diagnóstico foi de 41,91 anos (12-72), com maior prevalência em mulheres (79%). Os tipos histológicos encontrados foram: carcinoma papilífero (CPT) (56%), carcinoma folicular (CFT) (29%), medular (CMT) (9,0%) e anaplásico (6%). Dos 34 pacientes acompanhados, 24 (71%) realizaram PAAF. A tiroidectomia total ou quase total foi realizada em 88% dos pacientes. A estratificação de risco pós-operatória inicial foi: alto risco (48%), baixo risco (28%) e muito baixo risco (24%). A complicação pós-operatória mais prevalente foi o hipoparatireoidismo permanente em 17% e transitório em 13%. A terapia ablativa com radioiodo (I131) foi empregada em 19 dos 25 pacientes com câncer diferenciado operados (76%). conclusão: Nossa casuística foi concordante com dados da literatura em que houve prevalência no sexo feminino, CPT foi o tipo histológico mais frequente, a cirurgia de escolha foi tiroidectomia total ou quase total e RAIU foi indicada para os pacientes com CPT e CFT. A dificuldade enfrentada na realização de exames e tratamento de alto custo foi um obstáculo no seguimento adequado desses pacientes.

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Phosphoinositide-3-kinase (PI3K) inhibition increases iodide uptake in PCCL3 cells regardless of insulin presence

Souza ECL, Santos MCS, Braga WMO, Carvalho DPLaboratório de Fisiologia Endócrina Doris Rosenthal, IBCCF, UFRJ; Rio de Janeiro, Brazil

Background: Activation of the insulin/PI3K signaling pathway in TSH-stimulated thyroid cells reduces the sodium/iodide symporter (NIS) expression and selective inhibitors of PI3K, such as LY294002, significantly increase NIS mRNA expression. objective: We further investigated the role of PI3K pathway inhibition on iodide uptake reinduction in PCCL3 rat thyroid cell line that have lost the ability to uptake iodide by TSH withdrawal for 48h. Methods: PCCL3 cells were maintained in Coon’s modified Ham’s F-12 medium supplemented with 5% fetal bovine serum (FBS) containing bovine insulin (10 mg/ml), transferrin (5 mg/ml), and bovine TSH (1 mU/ml). Then, cells grown in 24-well dishes have been cultivated without TSH for 2 days, followed by medium with TSH in the presence or absence of insulin and/or LY294002, both in 5% or 2% FBS for 3 days. Cell iodide uptake (Na125I and 10 mM NaI for 45 minutes at 37°C) was normalized to the cell viability, measured by the MTT assay. Results: LY294002 significantly enhanced iodide uptake in PCCL3 cells either in the presence or absence of insulin. The inhibitory effect of insulin on iodide uptake was detected in both conditions, and the effect of LY294002 was significantly higher when cells were cultivated in 2% FBS, either in the presence or absence of insulin. conclusion: PI3K pathway is activated in thyroid cells cultivated in the presence of TSH and FBS, independent of insulin.

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Evaluación de la recurrencia del cáncer diferenciado de tiroides en grupos de bajo riesgo

Hurtado-López LM, Melchor-Ruan J, Zaldivar RR, Basurto KE, Pulido CA, Vázquez OR, Chapa AO, Etchegaray DA, MontesdeOca EClinica de Tiroides, Hospital General de Mexico; Mexico DF

antecedentes: Persiste la controversia entre la extensión quirúrgica a realizar para el manejo de cáncer diferenciado de tiroides en grupos de bajo riesgo. objetivo: Primario, Evaluar la recurrencia de cáncer diferenciado de tiroides en pacientes de bajo riesgo manejado con tiroidectomía total mas adyuvancia comparándola con hemitiroidectomía. Secundario, evaluar que clasificación identifica el grupo de bajo riesgo con menor recurrencia Material y métodos: Estudio retrospectivo, observacional, comparativo. Variable evaluada: recurrencia en pacientes de bajo riesgo (AMES bajo, MACIS < 6, TNM etapa I, DeGroot estadio I, MSKCC bajo) sometidos a tiroidectomía total mas adyuvancia (TT) comparado con hemitiroidectomía (HT). Se analizo por medio de chi cuadrada de Pearson y Exacta Fisher y Yates. Resultados: Se identificaron 240 pacientes. Para AMES se realizaron 23 HT (21.7% recurrencias) y 161 TT (4.3% recurrencias). Con MACIS 24 HT (20.8% recurrencias) y 146 TT (3.4% recurrencias). Con DeGroot 19 HT (15.8% recurrencias) y 73 TT (2.7% recurrencias). Para TNM (Etapa Clínica I) 22 HT (22.7% recurrencias) y 128 TT (5.5% recurrencias). Por MSKCC bajo, 12 HT (16.7% recurrencias) y 58 TT (6.9% recurrencias). Al comparar la recurrencia y el tipo de clasificacion, todas excepto DeGroot y MSKCC tuvieron diferencia estadística (p > 0.05), MACIS fue la clasificación que detecta más casos con menos recurrencia. conclusiones: La frecuencia de recurrencia en pacientes de bajo riesgo es menor al realizar tiroidectomía total más adyuvancia. MACIS es la clasificación más acertada, sin embargo ninguna permite realizar hemitiroidectomía con seguridad sin que se manifiesten recurrencias.


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Carcinoma adenoide cístico: armadilha em punção aspirativa por agulha fina em tiroide

De Paula EC, De Paula HM, Silva EC, Oliveira JC, De Paula GM1Hospital Araújo Jorge da Associação de Combate ao Câncer em Goiás; 2Laboratório Centro de Anatomia Patológica e Citopatologia; Goiânia, Brasil

Carcinoma adenoide cístico é responsável por aproximadamente 10% das neoplasias em glândulas salivares, porém o surgimento desta neoplasia em glândulas seromucinosas da submucosa traqueal ou laríngea é um evento raro. Além disso, a invasão tiroidiana por extensão direta de neoplasia primária da traqueia, apresentando-se clinicamente como massa tiroidiana, é acontecimento ainda mais raro. O objetivo é relatar um caso de carcinoma adenoide cístico de traqueia com invasão da tiroide. Paciente masculino, branco, 58 anos, referiu tosse sem expectoração, com irritação orofaríngea, disfagia, ausência de febre e que usava anti-hipertensivo. Foi solicitado RX de tórax que apresentou nódulos pulmonares. Duas biópsias com agulha grossa não atingiram as lesões. Encaminhado ao endocrinologista, foi realizado USG de tiroide e identificado nódulo de 3,0 x 1,3 x 2,5 cm. Foram realizadas duas punções com material insatisfatório. Na terceira punção, lobos D e E, o resultado foi de processo hiperplásico da tiroide, sugerindo neoplasia de células foliculares ou de células C. Foi realizada tiroidectomia total com exame per-operatório e o diagnóstico foi de carcinoma adenoide cístico. A tiroide pesou 18,0 g e mediu 9,0 x 4,0 x 1,8 cm. Aos cortes observou-se extensa lesão densa, branco-acastanhada, homogênea e medindo 2,5 x 1,2 cm. A histologia confirmou o diagnóstico de carcinoma adenoide cístico. A imunomarcação mostrou negatividade para calcitonina e tireoglobulina nas células tumorais. Paciente foi submetido à biópsia de traqueia e foi identificado carcinoma adenoide cístico. O presente caso serve de alerta para averiguar a possibilidade de neoplasia tiroidiana secundária quando os achados citológicos da PAAF não forem habituais.

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TP53 codon 72 polymorphism in thyroid nodules from Brazilian patients

De Paula EC2, Reis AAS1, Oliveira JC2, Silva DM3, Monteiro CD3, Cruz AD3, Saddi VA2-3

1Programa de Pós-Graduação em Biologia Celular e Molecular (Doutorado), Instituto de Ciências Biológicas, Universidade Federal de Goiás; 2Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás; Goiânia, Brazil

Background: In the past few years, an increasing number of thyroid nodules have been registered in different geographical regions, and such lesions constitute an important public health problem. Although, the majority of thyroid nodules are benign lesions, thyroid cancer is the most common endocrine malignancy, accounting for about 1% of all human malignant tumors. Polymorphism at codon 72 of TP53 gene results in either the arginine or proline form of the p53 protein. The functional significance of p53 polymorphism in thyroid carcinogenesis is still controversial. objective: to compare the frequency of TP53 Arg/Pro polymorphism in a group of 122 adult subjects presenting with thyroid nodules (which include multinodular goiter, adenomas and differentiated carcinomas), and a control group of 85 healthy subjects. Methods: Blood samples were collected from both groups and used for DNA extraction. Polymorphism genotyping was achieved by using polymerase chain reaction (PCR). Statistical analyses were performed using the SPSS software program (SPSS Inc.). Genotypic data were calculated using GenePopÒ web version 3.4 software. The chi-square test and Kruskal-Wallis were used to determine the possible differences between the groups. Results and conclusions: Allelic and genotypic frequencies were calculated for cases and controls, however, no significant statistical difference was demonstrated between the two groups (p > 0.05). Genotypic frequencies observed for the three different pathological conditions (multinodular goiter, adenomas and differentiated carcinomas) did not show significant differences, although the 72Arg/Pro genotype was most frequent in such conditions.

PO. 111

Dosagem de tireoglobulina em aspirado de linfonodo cervical no seguimento do carcinoma diferenciado de tireoide: série de casos

Bilhar FA, Batista AA, Razzolini L, Molinari AS, Azambuja Filho F, Gonçalves ICRServiço de Endocrinologia, Hospital Nossa Senhora da Conceição; Porto Alegre, Brasil

introdução: A dosagem de tireoglobulina em aspirado de linfonodo cervical tem sido ferramenta muito útil no seguimento pós-operatório do carcinoma diferenciado de tireoide para diagnosticar metástases cervicais. No Serviço de Endocrinologia do Hospital Nossa Senhora da Conceição, começamos a utilizá-la em julho de 2007. objetivo: Relatar a experiência do Serviço de Endocrinologia do Hospital Nossa Senhora da Conceição com a utilização da dosagem de tireoglobulina no aspirado de linfonodos cervicais em pacientes que fazem seguimento de câncer diferenciado de tireoide. Métodos: Série de casos. Resultados: De junho de 2007 a dezembro de 2008 foram puncionados 27 linfonodos em 18 pacientes que apresentavam suspeita de metástases cervicais no seguimento de carcinoma diferenciado de tireoide. A idade dos pacientes variou de 26 a 78 anos, com média de 45 anos no momento do exame. treza pacientes eram do sexo feminino e 5, do sexo masculino. O exame citopatológico mostrou resultado insatisfatório para análise em 7 linfonodos (25,9%). Em 3 casos, o diagnóstico de metástases foi feito exclusivamente pelo resultado da dosagem de tireoglobulina (tireoglobulina elevada no aspirado e citopatológico insatisfatório). Quatro casos foram encaminhados para tratamento cirúrgico, 3 deles com tireoglobulina elevada, que tiveram confirmação do diagnóstico pelo exame anatomopatológico; e 1 caso em que a tireoglobulina foi negativa, mas o citopatológico mostrou células linfoides com atipias (o diagnóstico anatomopatológico foi linfonodo reacional). Houve 2 linfonodos com conteúdo cístico, ambos apresentaram tireoglobulina elevada; 1 dos casos foi a tratamento cirúrgico com confirmação do diagnóstico de metástase de carcinoma papilar. conclusão: O percentual de exames citopatológicos insatisfatórios em linfonodos foi alto. A dosagem de tireoglobulina em aspirado de linfonodo cervical possibilitou diagnóstico de metástases cervicais em alguns casos em que o exame citopatológico isoladamente não seria útil. A presença de conteúdo cístico foi altamente sugestiva de malignidade.


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Tratamento de nódulos de tireoide por indicação estética através de alcoolização: série de casos

Bilhar FAServiço de Endocrinologia, Hospital Nossa Senhora da Conceição; Porto Alegre, Brasil

introdução: A alcoolização de nódulo de tireoide é uma alternativa terapêutica para tratamento dos nódulos de tireoide, sejam nódulos autônomos, cistos recidivantes, nódulos que causam sintomas compressivos ou queixas estéticas. O etanol tem a capacidade de provocar necrose de coagulação nas células foliculares e capilares intranodulares, acarretando redução da vascularização, fibrose e redução do volume nodular. No Serviço de Endocrinologia do Hospital Nossa Senhora da Conceição começamos a instituir o tratamento de nódulos de tireoide com alcoolização em outubro de 2006. Em nosso Serviço a principal indicação desse tratamento são os nódulos que motivam queixas estéticas. objetivo: Demonstrar os resultados do tratamento de nódulos de tireoide por meio da injeção percutânea de etanol com finalidade estética, avaliando o grau de redução do volume dos nódulos após o tratamento. Métodos: Estudo retrospectivo tipo série de casos. Foram incluídos todos os pacientes do ambulatório de endocrinologia que realizaram tratamento de nódulos de tireoide entre outubro de 2006 e fevereiro de 2008 através de injeção percutânea de etanol quando a queixa apresentada estava relacionada à aparência do nódulo na região cervical (considerada queixa estética) e que haviam feito punção desse nódulo com citologia satisfatória para análise e resultado negativo para células malignas. Foram excluídos os casos com hipertireoidismo e/ou sintomas compressivos relacionados ao nódulo. Comparou-se o volume nodular pré-tratamento e 1 mês após o final das sessões de alcoolização através do teste t pareado. Foi considerado significativo p < 0,05. Resultados: Quinze pacientes realizaram tratamento com alcoolização de nódulo de tireoide. Dois pacientes foram excluídos por não se tratar de tratamento com finalidade estética (1 com hipertireoidismo e 1 com sintoma compressivo). Foram avaliados os dados de 13 pacientes, sendo 12 do sexo feminino e 1 masculino. A média de idade foi 39,7 anos (DP: 16,07 – variação de 16 a 76); 76,9% dos nódulos eram mistos, e 23,1% cistos. Todos os pacientes com cistos já haviam sido submetidos à punção com esvaziamento do conteúdo, e foram encaminhados para alcoolização devido à recidiva. Foram realizadas em média 2,92 sessões de alcoolização em cada paciente (DP: 1,03 – variação de 1 a 4). A média do volume total de etanol injetado foi 65,16% do volume nodular pré-tratamento (DP: 28,75 – variação de 14,43 a 108,8). Houve redução significativa do volume nodular na avaliação realizada 30 dias após o término do tratamento (p < 0,001). A média de volume inicial dos nódulos era 11,64 ml (DP: 9,45), tendo reduzido para 4,5 ml (DP: 4,88). Houve redução percentual de volume de 68,74% (DP: 14,94 – variação de 41,53 a 92,41). O único efeito adverso foi dor na região cervical. conclusão: A alcoolização é uma opção terapêutica para os pacientes com nódulos de tireoide com queixa estética, resultando em redução significativa do volume nodular com poucos efeitos adversos além da dor.

PO. 113

Utilidade da dosagem de tireoglobulina em aspirado de linfonodo cervical no diagnóstico de carcinoma diferen-ciado de tireoide quando a punção não é diagnóstica: relato de dois casos pré-tireoidectomia

Bilhar FA, Batista AA, Razzolini L, Molinari AS, Azambuja Filho F, Gonçalves ICGServiço de Endocrinologia, Hospital Nossa Senhora da Conceição; Porto Alegre, Brasil

introdução: A dosagem de tireoglobulina em aspirado de linfonodo cervical tem sido utilizada com sucesso no diagnóstico de metástases no seguimento pós-operatório do carcinoma diferenciado de tireoide. A utilização desse método diagnóstico em pacientes não tireoidectomizados não é difundida. objetivo: Mostrar o papel da dosagem de tireoglobulina em aspirado de linfonodo cervical no diagnóstico de carcinoma diferenciado de tireoide em pacientes nos quais a punção aspirativa com agulha fina do nódulo de tireoide não estabeleceu o diagnóstico. Métodos: Relato de dois casos. Caso A: Paciente feminina de 29 anos com tireoide multinodular de crescimento recente e linfonodos cervicais palpáveis bilateralmente. Nódulos tireoideanos altamente suspeitos de malignidade (limites irregulares e microcalcificações). Realizada punção aspirativa com agulha fina sob controle ecográfico de dois nódulos tireoideanos, com resultado citopatológico negativo para células malignas e descrição de células foliculares típicas. Realizou-se então a punção de dois linfonodos, um deles no nível II à direita com 1,6 x 1,1 cm; o outro no nível III à esquerda com 1,1 x 0,7 cm; ambos sem hilo hiperecogênico e com microcalcificações. O exame citopatológico dos linfonodos foi negativo para células malignas. A dosagem de tireoglobulina no aspirado dos linfonodos foi 2798 ng/ml e 4012 ng/ml, respectivamente. Encaminhou-se a paciente para tratamento cirúrgico. O exame anatomopatológico indicou carcinoma papilar de tireoide multifocal com metástases em linfonodos cervicais bilaterais. Caso B: Paciente feminina de 65 anos com tireoide multinodular de consistência muito endurecida, crescimento recente e linfonodos cervicais palpáveis bilateralmente. Nódulos tireoideanos hipoecogênicos e com hipervascularização central. Realizada punção aspirativa com agulha fina sob controle ecográfico de dois nódulos tireoideanos, com resultado citopatológico indicando atipias nucleares, sendo suspeito mas não diagnóstico de neoplasia. Realizou-se então a punção de dois linfonodos, um deles no nível III à direita com 1,5 x 1,2 cm; o outro no nível IV à esquerda com 1,3 x 0,9 cm; ambos sem hilo hiperecogênico. O exame citopatológico indicou nos dois linfonodos metástases de carcinoma papilar de tireoide. A dosagem de tireoglobulina no aspirado dos linfonodos foi 800 ng/ml e 17,5 ng/ml; respectivamente. Encaminhou-se a paciente para tratamento cirúrgico. O exame anatomopatológico indicou carcinoma papilar de tireoide multifocal com metástases em linfonodos cervicais bilaterais. conclusão: A dosagem de tireoglobulina em aspirado de linfonodo cervical foi útil no diagnóstico de carcinoma diferenciado de tireoide em duas pacientes com alto grau de suspeição de malignidade nas quais a punção aspirativa com agulha fina do nódulo de tireoide não estabeleceu o diagnóstico. Em um dos casos relatados o exame citopatológico dos linfonodos não estabeleceu o diagnóstico.


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Microcarcinoma papilar de tiroides ¿se puede diferenciar el comportamiento agresivo inicial?

Munizaga F1-2, Lioi X1-2, Hidalgo S1, Munizaga C3

1Hospital San Borja-Arriarán, Unidad de Endocrinología; 2Universidad de Chile, Campus Centro; 3Universidad Católica del Norte; Santiago, Chile

introduccion: El manejo del microcarcinoma papilar (menor de 1 cm) es controvertido. Existe un grupo muy pequeño que presenta un comportamiento agresivo. objetivo: Evaluar elementos clínicos y ecograficos en microcarcinoma papilar (MCP) que permitan diferenciar inicialmente el comportamiento agresivo de esta patología. Material y metodos: Se evalúan pacientes que presentan nódulos < 0,001 En la ecografía la única diferencia significativa correspondió a la ubicación (se dividió en 3 tercios en posición anteroposterior, central región media, periférico tercios distales): 100% de los MCA estaban localizados en la periferia y 100% de MCH eran centrales. TSH: 3.32 uUI/mL (0.5-5.0), sin diferencias. conclusiones: El MCP de comportamiento agresivo se puede diferenciar con el de comportamiento habitual por clínica y ubicación ecográfica. ¿Es una entidad distinta?

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Nodulo intratiroideo ¿es solo de etiologia tiroidea?

Munizaga F1, Lioi X1, Rossi R2, Franco C, Munizaga C3

1Hospital San Borja-Arriarán, Universidad de Chile, Campus Central; 2Clínica Alemana; 3Universidad Católica del Norte; Santiago de Chile

introduccion: La presencia de nódulos tiroideos son frecuente en la población, en su estudio se solicitan evaluación tiroidea, antiTPO, y como diagnóstico de elección la punción tiroidea. Material y metodos: Se presentan 3 casos de de nódulo intratiroideo cuya evolución, diagnóstico y resultados de cirugía es de un adenoma paratiroideo intratiroideo. Resultados: Caso 1: Mujer 58 años, en tratamiento por nódulo tiroideo sólido de 6 mm en lóbulo derecho, de 16 años de evolución, exámenes iniciales TSH, T4 libre normales, se realizó punción: negativa para células neoplásicas, calcemia 9,2 mg/dl, hace 12 meses en control se pesquisa fosfatasas alcalinas aumentadas a expensas de fracción ósea cuyo estudio demostró cintigrafía ósea normal, calcemia 10,3 y PTH 72,8, niveles de vitamina D normal. Cintigrafía paratiroidea: posible adenoma inferior derecho. Se realiza cirugía, encontrándose el adenoma paratiroideo en ubicación intratiroidea. Caso 2: Mujer de 65 años, diabética tipo 2, en examen físico detecta bocio pequeño, ecografía demostró tiroides heterogéneas con múltiples imágenes quísticas, y con quiste prominente en lóbulo derecho de 8 mm, TSH 4,0, T4 libre normal, antiTPO negativos, calcemia 10,2 mg. A los 4 años de evolución sin cambios en la ecografía tiroidea en tratamiento con L-tiroxina 50 ug/día (TSH 1 U/mL), se pesquisa calcemia de 10,6 con PTH de 186,4, cintigrafía paratiroidea negativa. Densitometría ósea osteopenia de columna y caderas, se inicia alendronato, y por persistir con aumento de calcemia a 11 se decide indicar cirugía. Se realiza tiroidectomía total, encontrándose adenoma paratiroideo intratiroideo derecho y carcinoma papilar de tiroides incidental de 0.6 mm, el resto de la glándula hiperplasia multinodular folicular. Caso 3: Mujer de 55 años solicita segunda opinión, en tratamiento por 10 años por nódulo sólido en el lóbulo derecho de 7 mm, sin cambios en este tiempo, Se reevalúa encontrándose nodulo sólido vascularizado, TSH y T4 libre bajo terapia con L-tiroxina normales. Calcemia 10,7 PTH 138,5. Cintragrafía paratiroidea: posible adenoma paratiroidea derecha. Se somete a cirugía. conclusiones: En el estudio de nódulo tiroideo, especialmente de ubicación posterior es importante descartar un adenoma paratiroideo ya que modifica la conducta terapéutica.

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Carcinoma medular de tireoide com características de anaplásico

Viégas MA, Caldas G, Pinho J, Padilha MUnidade de Endocrinologia e Diabetes do Hospital Agamenon Magalhães, Universidade de Pernambuco; Recife, Brasil

introdução: Carcinoma medular é o mais agressivo dos cânceres diferenciados de tireoide. Casos esporádicos correspondem a 80% e se apresentam de forma mais agressiva. objetivo: Relatar caso de carcinoma medular de tireoide com evolução agressiva. Caso: AMCA, 40 anos, feminino, perda de 5 kg em três meses, ultrassonografia da tireoide: nódulos hipoecóicos de 1,0 x 1,0 x 1,0 cm no terço inferior do lobo direito, de 2,5 x 2,5 x 2,5 cm no terço inferior do lobo esquerdo e de 1,2 x 0,6 x 1,0 cm em istmo; imagens sólidas em cadeias ganglionares. Punção nódulos: bócio adenomatoso no direito e carcinoma anaplásico no esquerdo e istmo. Punção linfonodo cervical direito: metástase ganglionar. Realizou apenas um ciclo de quimioterapia com cisplatina 100 mg/m2 e adriamicina 60 mg/m2, pois biópsia de nódulo lobo esquerdo evidenciou carcinoma medular de tireoide. Calcitonina sérica = 1147 pg/ml; CEA = 15,8 ng/ml. Tomografia de pescoço: lesões focais em lobos tireoidianos, extensão para mediastino superior; linfonodomegalias nos sítios II, III e IV à esquerda, IV à direita, região supraclavicular bilateral, mediastino anterior e superior e cadeia mamária interna direita. Cintilografia óssea: hipercaptação focal sugestiva de infiltração metastática em crânio, coluna dorsal (D6), sexto arco costal anterior à direita, terços médios dos fêmures, ísquio e ilíaco esquerdo. Resultados: Submeteu-se à tireoidectomia total, esvaziamento cervical bilateral e ressecções de implante pleural à direita e nervo laríngeo recorrente inferior esquerdo. Histopatológico: carcinoma indiferenciado. Imunoistoquímica: positiva para cromogranina A, fator de transcrição tireoide/pulmão, tireoglobulina, calcitonina e Ag de proliferação celular Ki-67, confirmando diagnóstico de carcinoma medular. conclusões: Este caso ilustra evolução agressiva de carcinoma medular de tireoide, com múltiplas metástases ósseas, e a importância da imunoistoquímica no diagnóstico.


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Clinical and histological evaluation of 179 papillary carcinomas operated at the same Institution

Augusto GA1, Shiang C2, Camargo RY1, Tomimori E1, Ferraz A3, Knobel M1, Gehard R2, Marui S1

1Unidade de Tireoide, LIM 25, Disciplina de Endocrinologia; 2Departamento de Patologia; 3Departamento de Cirurgia de Cabeça e Pescoço; Hospital das Clínicas, Faculdade de Medicina, Universidade de Sao Paulo; Sao Paulo, Brazil

Thyroid carcinoma is the most frequent endocrine cancer and papillary carcinoma is the most common histological type. objective: To evaluate all cases of papillary carcinoma operated at the same Institution (Hospital das Clínicas-Faculdade de Medicina-University of Sao Paulo-Brazil). Methods: Between 1994-2008, we retrospectively analyzed clinical and histology patterns through medical registers. Results: We reviewed 179 cases (21 M: 158 F) with mean age of 46 years-old. Mean tumor size was 2.5 cm. Classical subtype corresponded to 73.5% of cases, follicular variant 17%, tall cells 2.8% and others subtypes 6.7%. Forty-three percent of cases had multifocal lesions. Lymph node metastasis at surgery were detected and resected in 24%. Thyroid capsule invasion was noted in 12.2%, neural invasion 12% and vascular invasion 20.3%. Fine needle aspiration biopsy (FNAB) was performed previously to surgery in 103 nodules, being 90.3% malignant or suspicious of papillary carcinoma and 8.7% follicular neoplasia. Between follicular lesion at FNAB, 66.6% resulted in follicular subtype and the remaining in classic subtype of papillary carcinoma. Only one patient had suspicious of papillary carcinoma at FNAB, but histological diagnosis was goiter lesion, leading to false positive diagnosis of 1%. conclusions: Our Institution is in agreement to literature, according to age, gender and histological types of papillary carcinoma affected patients. We also showed a low rate of false-positive FNAB, which emphasizes the importance of FNAB previously to surgery. It is noteworthy the high frequency of multifocal lesions in our cohort, denoting the importance of histological findings to better follow-up these patients.

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Histopathologic, prognostic and clinic features of lung metastatic papillary carcinoma of thyroid: retrospective study of 17 patients

Andrade JA, Odawara AF, Barella JLS, Villagelin D, Hanaoka N, Santos RB, Romaldini JHEndocrinology and Metabology Division, Hospital e Maternidade Celso Pierro, Pontifícia Universidade Católica de Campinas; Campinas, Brazil

Background: The papillary thyroid carcinoma (PTC) shows with lung metastases (LM) at the diagnosis at 1% to 8% of times. Few data are available on presentation, treatment, and outcomes in LM patients. objective: Evaluate the histopathologic, prognostic and clinic features of the PTC with LM. Methods: This retrospective study evaluated 17 patients, followed through 1995 to 2007, with PTC and LM. All patients undergone total thyroidectomy, lymphadenectomy, diagnostic and post-therapy 131I whole-body scans (WBS), thyroid hormone supressive treatment and followed with serum thyroglobulin and serum thyroglogulin antibody besides chest computadorized tomography/magnetic nuclear resonance (CT/MNR). Results: Seventeen patients (15 women, 2 men), mean age 36.29 years (20 to 54), with 52.94% (9) classic PTC; 29.49% (5) follicular variant; 5.88% (1) sclerosant variant, 5.88% (1) tall cells variant and 5.88% (1) classic PTC with anaplastic areas; mean tumor size 1.8cm (0,1 to 4,2); 47.06% (8) multicentric; 35.29% (6) capsular invasive and 5.88% (1) vascular invasive. Local and lymph nodal invasion were of 23.53% (4) and 64.71% (11), respectively. The diagnosis of LM through the first diagnostic WBS, post-therapy WBS, following dianostic WBS and chest CT were of: 29.41% (5); 41.17% (7); 11.76% (2) and 17.65% (3). Mean 131I dose 420.59mCi (100 to 700mCi). Estimulated thyroglobulin positive in 63.64% (7), thyroglogulin antibody present in 27.27% (3) and chest CT/MNR with LM in 36.36% (4). Free disease survival mean time 40 months (12 to 102) with no deaths. conclusion: Although being a rare presentation of the PTC and without deaths in our study, the LM requires close evaluation of the patient to correct diagnosis and follow up.

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Carcinoma papilífero é a lesão maligna mais frequentemente encontrada nos nódulos tireoideos com citologia in-determinada

Monte L, Seoane LA, Tomimori EK, Knobel M, Camargo RYAUnidade de Tireoide, Disciplina de Endocrinologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; São Paulo, Brasil

introdução: A punção aspirativa por agulha fina (PAAF) é o exame mais sensível para o diagnóstico dos nódulos tireoideos, porém, em 15% a 20% dos casos, a citologia é indeterminada para neoplasia folicular1,2. objetivos: Estudar os nódulos com citologia indeterminada submetidos à cirurgia e determinar a prevalência e o tipo histológico das lesões encontradas. Métodos: Foi realizada uma análise retrospectiva dos pacientes atendidos na Unidade de Tireoide do Hospital das Clínicas da Faculdade de Medicina da USP, no período de fevereiro de 1997 a abril de 2008, que apresentaram nódulos com citologia indeterminada e submetidos a tratamento cirúrgico. Resultados: De 428 tireoidectomias realizadas nesse período, 135 (31,5%) apresentaram citologia indeterminada para neoplasia folicular. Destes, 100 (74%) tiveram diagnóstico anatomopatológico benigno e 35 (26%), maligno. Dentre as lesões malignas, 26 (74,3%) corresponderam a carcinoma papilífero, 7 (20%) a carcinoma folicular e 2 (5,7%) a carcinoma medular. Das lesões benignas, 75 (75%) tiveram diagnóstico anatomopatológico de bócio adenomatoso, 32 (32%) de adenoma folicular, 15 (15%) de tiroidite crônica linfocítica e 1 (1%) de bócio disormoniogênico. conclusão: Em nossa casuística, 26% das citologias indeterminadas eram malignas, sendo que o carcinoma papilífero foi a lesão maligna mais encontrada. Referências: Rago T, et al. Combined clinical, thyroid ultrasound and cytological features help to predict thyroid malignancy in follicular and Hurthle cell thyroid lesions: results from a series of 505 consecutive patients. Clin Endoc. 2007; 66:13-20; Sahin M, et al. Prevalence and prediction of malignancy in cytologically indeterminate thyroid nodules. Clin Endoc. 2006; 65:514-8.


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Cambios bioquímicos y morfológicos durante la inhibición e involución del bocio por el 2-iodohexadecanal en tiroi-des de rata

Thomasz L1, Toro D1, Oglio R1, Villamar S1, Fernandez M4, Jahn G3, Pagotto R4, Pignataro O4, Pisarev M1-2, Juvenal G1

1División Bioquímica Nuclear, CNEA; 2F. de Medicina, UBA; 3Larlac; 4IBYME; Argentina

introducción: El iodo es utilizado por la tiroides para sintetizar hormonas tiroideas pero además posee un rol regulatorio a través de la síntesis de lípidos iodados. Entre estos la 6-iodo-delta-lactona del ácido araquidónico (IL-δ) y el 2-iodohexadecanal (IHD) inhiben varios parámetros tiroideos. objetivo: Analizar los cambios bioquímicos y morfológicos durante la inhibición e involución del bocio por el 2-iodohexadecanal. Resultados: Ensayos de inhibición del bocio inducido: Ratas fueron inyectadas 10 días con MMI (5 mg/día) y MMI + IHD 1 µg, 5 µg, 10 µg, 20 µg. El MMI provocó un aumento del peso tiroideo del 176% (p < 0.05) y el IHD revirtió el efecto del MMI de manera dosis dependiente, con una inhibición del 20% (p < 0.05) a una dosis de 20 µg por día. El MMI provocó un incremento en los niveles de TSH y AMPc respecto a los controles (p < 0.01) mientras que el tratamiento con IHD redujo los niveles de AMPc (75% de inhibición p < 0.01). Al estudiar el antígeno de proliferación celular PCNA por western blot obtuvimos una inhibición del 25% por parte del IHD (p < 0.05 MMI versus MMI + IHD). ensayos de involución: El bocio fue inducido por la administración de MMI 10 días, luego se interrumpió el tratamiento y se inyectó solución salina, IHD o KI. El IHD produjo una disminución del peso tiroideo (36% a los 3 días, 27% luego de 7 días, 30% luego de 10 días, p < 0,01), del número de células y de la altura del epitelio glandular. conclusión: El IHD previene el crecimiento glandular y provoca la involución del bocio preformado.

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The diagnostic value of PTH concentration in the ultrasound-guided fine-needle aspiration of cervical nodules suspi-cious for parathyroid adenoma

Seoane LA, Monte L, Tomimori EK, Knobel M, Camargo RYAEndocrine Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil

Background: Although the sensitivity of imaging studies is high in solitary parathyroid adenomas, negative results are inevitable (1). objective: The aim of this study is to evaluate the utility of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) and measurement of parathyroid hormone (PTH) in the needle-washout as a preoperative localization procedure. Methods: The study group consisted of 10 patients that underwent US study of the neck which suggested the presence of a solitary parathyroid adenoma. All patients underwent US-FNA measurement of PTH in the needle-washout. The needle (21 gauge) was rinsed with 1 ml of normal saline solution and the washout was subjected to measurement of the PTH levels (FNA-PTH). The results of FNA-PTH were compared with serum PTH levels. Results: Detectable amounts of FNA-PTH were found in all ten patients and in nine of them, the FNA-PTH was higher than the serum levels. Seven patients underwent parathyroidectomy with confirmed parathyroid adenoma. conclusion: We concluded that PTH measurement in the fine-needle aspiration washout is a useful technique for diagnosis of parathyroid adenoma and can be more accurate to detect parathyroid adenoma than the other imaging studies (2). References: 1. Erbil Y, et al. Use of preoperative parathyroid fine-needle aspiration and parathormone assay in the primary hyperparathyroidism with concomitant thyroid nodules. Am J Surg. 2007; 193 (6):665-71; 2. Barczynski M, et al. Technetioum-99m-sestamibi subtraction scintigraphy vs. ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach. Clin Endocrinol (Oxf). 2006; 65 (1):106-13.

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Lipopolysaccharide stimulates cell proliferation and modifies cell cycle-related proteins in the FRTL-5 thyroid cell line

Nazar M, Nicola JP, Vélez ML, Pellizas CG, Masini-Repiso AMCentro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica Facultad de Ciencias Químicas, Universidad Nacional de Córdoba; Córdoba, Argentina

Lipopolysaccharide (LPS) elicits several immediate proinflammatory responses in peripheral blood leukocytes via Toll-like receptor 4 (TLR4). However, this cell wall compound of gram-negative bacteria induces the expression of different genes in numerous cell types. We previously demonstrated the functional expression of the LPS receptor, TLR4 and the accessory molecules CD14 and MD2 at the plasma membrane in the FRTL-5 rat thyroid cell line. In these cells, LPS induced up-regulation of thyroglobulin and Na +/I- symporter gene expression. Increasing experimental evidence indicates that chronical inflammatory processes that may lead to tumorigenesis are mediated in part through recognition of stimulus by TLR4. This study aimed to analyze the action of LPS on FRTL-5 thyroid cell proliferation. We revealed that LPS increased the cell proliferation rate measured by dilution of the CFSE intracellular dye and DNA-incorporation of 3H-thymidine. The impact of LPS treatment on proteins related to cell cycle control, as cyclins, cyclin-dependent kinases (CDKs), and CDK-inhibitors was tested. LPS stimulated the protein expression of cyclin D1 and D3, CDK6 and CDK4. Paradoxically, the expression of the CDK-inhibitors p27 and p15 is also increased. Because it is known that the cyclin D1 promoter contains a consensus site for NF-kB, a well identified mediator of LPS action, the role of LPS on cyclin D1 gene expression should be explored. In conclusion, we evidenced that thyroid cells are able to respond to the proliferative stimulus of LPS, a fact that supports a role of the endotoxin as a potential modifier of thyroid cell replication.


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Cancer papilar tiroideo con metástasis ósea vertebral asociado a paraplejía: caso clinico

Barberán M, Arias M, Cordero F, Liberman CServicio de Endocrinología, Hospital Clínico Universidad de Chile; Santiago do Chile

El cáncer diferenciado de tiroides (CDT) tienen sobrevida a 10 años de 80% a 95%, pero cuando hay metástasis óseas esta disminuye a un 13 a 21%. Las metástasis óseas de CDT ocurren en un 2% a 13%. Son mas frecuentes en cáncer folicular (7%-28%) comparado con cáncer papilar tiroides (1,4%-7%); y reducen además la calidad de vida. caso clínico: Hombre de 55 años, peruano, residente en Chile. Estando en buenas condiciones generales, comienza en junio/2008 cuadro caracterizado por debilidad de extremidades inferiores, rápidamente progresiva, llegando a la postración a los 3 meses por paraplejia. De los antecedentes destaca tiroidectomía subtotal izquierda hace 12 años en Lima, el resultado de la biopsia se desconoce. En dicha oportunidad cursa eutiroideo, no recibió radioyodo ni terapia sustitutiva. examen físico: cicatriz tiroidectomía, masa palpable 2 cm. cadena yugular izquierda sugerente de adenopatía. Paraplejia fláccida de extremidades inferiores, reflejos osteotendineos ausentes y sensibilidad táctil disminuida a partir de T12. Radiografía columna lumbar muestra acuñamiento de vertebra T12. TSH y T4L normales, tiroglobulina 24,7 ng/ml, anticuerpos antitiroglobulina < 20 m UI/ml. La RNM de columna confirmó proceso expansivo de T12 con fractura y compresión medular de aspecto metastático. Cintigrama óseo: imagen osteoblática en T12 y sacro ilíaca izquierda. La biopsia percutánea de T12 e inmunohistoquímica concluye la presencia de metástasis ósea de carcinoma folicular tiroideo, tiroglobulina (+), keratina 7 y 19 (+), TTF1 (+). Ecotomografía tiroides: lóbulo derecho sin lesiones focales. Lecho tiroideo izquierdo con múltiples adenopatías de 12 a 20 mm. Se realiza fijación y tumorectomia de T10 a L2, con buena evolución motora y sensitiva de extremidades inferiores. Posteriormente se realizó tiroidectomía total con vaciamiento ganglionar central y lateral, programándose terapia con radioyodo 200 mCi. Biopsia demostró metástasis de carcinoma papilar en 22 de 40 ganglios e hiperplasia coloidea lóbulo derecho. comentario: Se presenta caso clínico de cáncer papilar con metástasis ósea vertebral asociado a paraplejia. El manejo agresivo de la lesión vertebral junto con tiroidectomía total y vaciamiento ganglionar ampliado permitieron una recuperación casi completa del compromiso neurológico. Este caso ilustra una evolución atípica del cáncer papilar tiroídeo y la importancia de su manejo multidisciplinario.

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Arginase II and nitric oxide sintase (NOS): pathogenesis pathways of thyroid tumors

Sousa MSA, Latini FRM, Cerutti JMGenetic Basis of Thyroid Tumors Laboratory, Division of Genetics and Division of Endocrinology, Federal University of Sao Paulo; Sao Paulo, Brazil

Background: We have previously shown increased expression of Arginase II (ARGII) in thyroid carcinomas compared to normal thyroid and benign lesions. Although ARGII expression is associated with a malignant phenotype, its role at this pathogenesis is still unknown. ARGII participates on the urea cycle competing with NOS (nitric oxide synthase) for L-Arginine. objective: we investigated whether this molecular cross-talk among ARGII and NOS might elucidate the role of ARGII on the pathogenesis of thyroid cancer. Methods: RNA-mediated gene silencing (siRNA) was performed for transient silencing of ARGII in human follicular thyroid tumor cells (WRO). Results: Using quantitative PCR and Western blot analysis, we confirmed that three distinct regions of ARGII were effective on the knock down of target mRNA levels by 50% to 95%. We also found that knocking down ARGII caused reduction of ARGII activity with simultaneous higher levels of NO (nitric oxide). Interestingly, NO can both promote and inhibit tumour growth. We here showed that silencing of ARGII reduced p21 and Ki67 expression concomitantly with increased apoptosis and reduction of ERK phosphorylation, both suggesting inhibitory effects of NO. Since NO is a donor of oxidative stress, we hypothesized that oxidative stress may be the mechanism by which ARGII is induced in thyroid carcinomas. We found that ARGII knock down modulates expression of genes associated with oxidative stress such as HIF1. conclusion: Our results indicate a strong correlation between ARGII and NOS by respectively promoting and suspending thyroid tumors progression. We also suggest that its pathway is activated through oxidative stress.

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Radioprotective role of 6-propyl-2-thiouracil (PTU) in thyroid cells

Perona M1, Dagrosa A1, Pagotto R2, Casal M1-3, Pignataro O2, Pisarev M1-4, Juvenal G1

1Dept. of Radiobiology (CAC), National Atomic Energy Commission; 2IByME-CONICET; 3Instituto de Oncología “Angel H Roffo”, University of Buenos Aires; Buenos Aires, Argentina

introduction: Epidemiologic studies have shown that the exposition to high external radiation doses increases thyroid neoplastic frequency, especially when given during childhood or adolescence. The use of radioprotectors, drugs that protect cells from the damage caused by radiation therapy, could be useful to prevent the development of thyroid tumors in patients treated with this therapy. objective: To study the effect of propylthiouracil (PTU) as a radioprotector in the thyroid gland. Methods: FRTL-5 cells were exposed to γ-irradiation at different doses (1 to 8 Gy) in the presence or absence of PTU (0.5 and 1 mM). Cell surviving fractions (SF) were determined by the standard in vitro colony formation assay. Results: Cell viability was evaluated by MTT assay. PTU didn’t affect the viability “per se”. The SF was increased in the presence of PTU, in both concentrations. The ratio PTU vs. control (5 Gy) was 1.3 and 1.5 respectively. cAMP levels were measured after incubating the cellular line with different concentrations of PTU (0; 0.1 mM; 0.5 mM) at different times (5, 24, 48 and 72 hours). A peak was observed at 24 hs in extracelullar levels when cells were incubated with PTU 0.5 mM (52.67 ± 5.55 fmol/µg prot vs. control: 41.91 ± 6.01 fmol/µg prot). Catalase activity was increased in irradiated cells (1 and 5 Gy) treated with PTU. conclusion: PTU is a radioprotector for thyroid cells and could exert its effect through cAMP increasing the activity of antioxidant enzymes.


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Detecção da mutação BRAF em carcinoma papilífero de tiroide comparado por SSCP e PCR nested

Da Silva MJ, Fuziwara CS, Kulcsar MA, Friguglietti CU, Araujo-Filho VJF, Yoon HS, Logullo AF, Kimura ETDepartamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas. Universidade de São Paulo; São Paulo, Brasil

A mutação do gene BRAFT1799A é a alteração genética mais frequente em carcinoma papilífero de tiroide (CPT). Pelo fato de estar associada ao pior prognóstico clínico, é importante estabelecermos métodos simples e robusto que determinem essa mutação. Neste estudo comparamos duas metodologias de detecção da mutação BRAFT1799A em tecido tumoral de CPT emblocado em parafina. Extraímos DNA de blocos histológicos de 102 pacientes com diagnóstico de CPT e analisamos a mutação BRAF pelos métodos SSCP e PCR-nested. No SSCP, o segmento do éxon 15 do gene BRAF foi amplificado por PCR (231pb), desnaturado com NaOH a 95°C, aplicado em gel MDE 0,6%. Após a coloração com nitrato de prata, analisamos a migração das bandas baseadas em um controle positivo. No PCR-nested, o DNA foi amplificado em duas reações de PCR sucessivas na região que contém o sítio de mutação BRAFT1799A; digerido com XbaI e o produto observado em gel SDS-PAGE 12%. Dos 102 pacientes, o SSCP identificou 34/102 (33%) com mutação BRAFT1799A e o PCR-nested 43/102 (42%). Observamos que 68/102 pacientes negativos para mutação por SSCP, 21/68 foram identificados como positivos por PCR-nested; por outro lado, 4/34 mutação positiva por SSCP não foi detectado por PCR-nested. Considerando, o SSCP como “gold standard”, PCR-nested apresenta sensibilidade de 90% e especificidade de 74%; enquanto PCR-nested “gold standard”, o SSCP apresenta sensibilidade de 61% e especificidade 93%. conclusão: O PCR-nested apresentou alta sensibilidade, podendo ser útil para determinar a mutação BRAF na prática clínica de pacientes com CPT. Apoio financeiro: Capes, Fapesp e CNPq.

PO. 127

High prevalence of suspicious fine-needle aspiration cytology in thyroid nodules associated with positive thyroglobulin antibodies but not with thyroid peroxidase antibodies

Sá MBR1, Villagelin D1-2, Santos RB1, Cunha M1, Romaldini JH1-2

1Departament of Endocrinology, Pontifícia Universidade Católica de Campinas, Campinas, Brazil; 2Hospital Servidor Publico Estadual; Sao Paulo, Brazil

objective: The relationship between thyroid autoimmunity and cancer is still uncertain. The development of antibodies to thyroid peroxidase and thyroglobulin is one of the main features of autoimmune thyroid diseases. Therefore, we assessed the association between presence serum anti-thyroperoxidase antibody (TPOAb) and anti-thyroglobulin antibody (TgAb) with thyroid cancer in a retrospective series of unselected thyroid nodules submitted to fine-needle aspiration cytology (FNAC). Methods: Ultrasound (US)-guided FNAC were obtained from 224 unselected consecutive patients with thyroid nodules. Cytological results were classified in three classes of increased risk of malignancy, low risk or benign (class I), indeterminate risk (class II) and suspect or malignant (class III). TPOAb and TgAb were measured using highly sensitive radioimmunoassay. Results: There is no difference according the class of FNAC and determinations of serum TPOAb (69 positive) and TgAb (50 positive). Thirty one patients had thyroidectomy and thyroid cancer was found in 14 patients. By multivariate logistic regression analysis presence of serum TgAb conferred a significant risk [odds ratio (OR): 2.76, 95% confidence interval (CI) of 1.20-6.33] for cancer independently from age and sex. Presence of TPOAb did not shown any association with thyroid cancer, OR of 0.78 CI (0.44 – 1.37) or thyroid function. conclusions: Autoimmune phenomena determined by presence of TgAb positive are not an infrequent finding in thyroid cancer. The presence of TgAb positive indicates an increased risk of neoplasia in unselected thyroid nodules but further studies with a different design are needed for a definitive histological proof.

PO. 128

Proliferacion epitelial: idetificacion de factores que aumentan el riesgo de malignidad

Corino M, Migliano M, Morelli S, Bacchini V, Moreno A, Padin RHospital Nacional Prof. Alejandro Posadas; Buenos Aires, Argentina

objetivo: Determinar los factores con riesgo de malignidad en relación al hallazgo citológico de proliferación epitelial. Material y método: Se estudiaron retrospectivamente 46 pacientes con diagnostico citológico de proliferación epitelial entre 2000 – 2008 que fueron intervenidos quirúrgicamente. Se analizaron: edad, sexo, tamaño nodular, TSH y ATPO. Se utilizo la tabla de correlación de 2x2 para el analisis estadistico Resultados: 46 pacientes 42 mujeres y 4 varones edad r: 14-73 años. Media 43 años presentaron: grupo I n 35 (76.1%) patología benigna grupo II n 11 (23.9%) patología maligna. Grupo I: 35 pacientes (14 adenomas foliculares, 12 hiperplasias, 4 adenomas de Hurthle y 5 tiroiditis). Mujeres 33/35 (94%) y varones 2/35 (6%). 13/35 pacientes (37%) > de 45 años 7/35 (20%) tuvieron un nódulo > a 4 cm. TSH > de 3 mUI/ml en 2/35 (5.7%). ATPO (+) 5/35 (15.6%). Grupo II: 11 pacientes 5 /11 CA. Medular 6/11 Ca. Papilar. Mujeres 9 (82%) varones 2 (18%). 8/11 (72%) > de 45 años p = 0.038 ES; 3 /11 (28%) > de 45 años, uno menor de 20 años. 3/11 (27%) tuvieron un nódulo > a 4 cm. TSH > de 3 mUI/ml en 4/11 pacientes (36.3%) p = 0022 ES. ATPO (+) en 4 pacientes (40%). conclusiones: La prevalencia de carcinoma con diagnostico citológico de proliferación epitelial fue 23.9%. El valor de TSH mayor a 3 y la edad mayor a 45 años correlacionaron estadísticamente para mayor riesgo de malignidad. Los otros factores estudiados sexo, tamaño nodular y ATPO no fueron estadísticamente significativos.


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Presentación atípica del cancer medular de tiroides (CMT)

Herrera M, Ramos C, Veliz J, Brantes S, Villegas P, Barría M, Wohllk NSección Endocrinología Servicio Cirugía Servicio Anatomía Patológica Hospital del Salvador Universidad de Chile IEMA; Santiago do Chile

Aproximadamente el 5% del síndrome de Cushing ectopico (EAS) son CMT y en el CMT el EAS solo se presenta en el 0,7% de los casos. caso clínico: Hombre de 55 años; hace un año con aumento prorgresivo de volumen cervical anterior, asociado a baja de peso de 8 kilos. Hace 3 meses aumento de volumen en extremidades derechas. Posteriormente presenta celulitis en extremidad inferior derecha, y se pesquisa Diabetes Mellitus. examen físico: IMC 31, PA 150/90 mmHg, gran masa cervical anterior y lateral, edema en extremidades, Pemberton (+). exámenes preoperatorios: K + 2,6 mEq/l, alcalosis metabólica, Hcto 33%, Hb 10,5 g/dl, VHS 64, albúmina 2,6 g/dl, TSH 0,86 UI/ml, T4L 0,78 ng/dl, Calcitonina 19256 pg/ml (N < 9,6), CEA 775 ng/ml ( < 4,2), Cortisol basal 48 µg/dl (N 7-22), Cortisol post dexametasona 1 mg 45,3 µg/dl (N < 1,8 µg/dl), ACTH 104 pg/ml (N 10-46), Cortisol libre urinario (CLU) basal 1584 µg/gcreat (N 20-100), Test de frenación con Dexa 8 mg por 2 días, CLU 48H 1270 µg/gcreat, Cortisol plasmático 48H > 50 µg/dl, TAC de cuello: tiroides aumentado de tamaño a expensas del lóbulo tiroideo derecho e istmo, múltiples imágenes nodulares. TAC de tórax nódulo de 14 mm LSD y en TAC de abdomen hígado con masa hipodensa de 5 cm. tratamiento: uso de Ketoconazol; Cirugía paliativa: tiroidectomía total, disección cervical y mediastinica. Anatomía patológica: tumor tiroideo con múltiples adenopatías, tinción rojo congo (+), CMT. Paciente fallece a los 21 días de la cirugía. conclusiones: CMT es una patología grave, el pronóstico es peor cuando existe compromiso ganglionar y lo es aún más cuando hay EAS. La hipokalemia es un indicador de enfermedad activa y diseminada. La mortalidad en presencia de EAS es de un 80% a corto plazo.

PO. 130

Peripheral thyroglobulin mRNA quantification in patients with differentiated thyroid cancer and positive anti-TG antibodies

Possato-Fernandes R, Rubio IGS, Camargo RY, Tomimori EK, Knobel M, Medeiros-Neto GThyroid Unit (LIM 25), Endocrine Division, University of Sao Paulo Medical School; Sao Paulo, Brazil

Periodic evaluation through imaging examinations and serum thyroglobulin (sTG) measurements are recommended for careful follow-up of patients with differentiated thyroid carcinoma (DTC). Anti-TG antibodies (Ac-TG) prevalence in patients with DTC is 15% to 25% and would impair, partially, the sTG use as a tumor marker. An alternative method to identify the tumor recurrence is the thyroid cells detection in peripheral blood, through TG messenger RNA quantification (mRNA-TG). The aim of this study was to evaluate the mRNA-TG peripheral blood quantification significance as a complementary diagnostic method in the long term follow up of patients with DTC and positive Ac-TG. Seventeen DTC patients with Ac-TG were included. Blood samples were collected yearly during 6 years after L-T4 withdrawal (TSH ≥ 30 µU/mL). We detected 33 samples with Ac-TG:16 samples from 6 disease free patients (DF), 10 samples from 4 patients with lymph nodes metastasis (LM) and 7 samples from 4 patients with distant metastasis (DM). GAPDH was the housekeeping gene used to calculate the mRNA-TG concentrations by real time PCR. The mRNA-TG levels were: DF patients 1.07 (0.01-2.31)UA, LM patients: 1.83 (0.36-3.71) UA and DM patients: 0.33 (0.03-3.41) UA. The sTG levels were: DF patients 0.5 (0.50-2.80) ng/mL, LM patients 17.25 (0.50-53.20) ng/mL and DM patients 301.80 (6.50-1487.00) ng/mL. The mRNA-TG did not distinguish the clinical stage as did sTG (p≤0.01). In twelve samples, sTG was undetectable (9 from DF patients and 3 from LM). Similar levels of mRNA-TG were detected in both group of patients [DF:1.59 (0.46-2.31)UA and LM:1.11 (0.36-2.55) UA]. All DM patients had undetectable sTG. In conclusion mRNA-TG is not an adequate marker to detect DTC recurrence.

PO. 131

Factores de riesgo de falsos negativos en la punción de tiroides con aguja fina

Quiroga S, De Candia L, Nebel E, Moloeznik L, Olguín M, Chiganer G, González Garcia M, Brunás O, Novelli JLCentro de Tiroides “Dr. José Luis Novelli”; Rosario, Argentina

introducción: La punción de tiroides (PAAF) genera controversias cuando se informa patología benigna y en la histología se diagnostica un carcinoma tiroideo [F (-)]. Objetivo. Evaluar factores de riesgo asociados a F (-) en el carcinoma papilar (CPT). Método: Agosto 1986 – Diciembre 2007. De 2221 pacientes con PAAF se seleccionaron los casos operados por CPT (n = 297). Se incluyeron 181 pacientes con resultados verdaderos positivos [V (+) ] (n = 157) y los genuinos F (-) (n = 24). Se excluyeron los hallazgos de CPT (n = 43), las PAAF Indeterminadas (n = 64) y las Insuficientes (n = 9). Método de obtención del material: palpación o guía ecográfica. Las PAAF fueron analizadas por diferentes citólogos, mientras que la histología fue realizada por un único equipo. factores de riesgo considerados: edad, sexo, nódulo: diámetro, uninodularidad/multinodularidad, sólido/quístico/mixto y método de obtención. Se estimó la medida del Odds Ratio (OR) y su respectivo intervalo de confianza (P < 0.05). Resultados: Los nódulos quísticos proveyeron casi 8 veces más probabilidad de F (-) que los sólidos, OR = 7.9 (1.2 – 54.6). La naturaleza mixta no fue un factor de riesgo de F (-), OR = 1.6 (0.4 – 5.7). La multinodularidad tuvo mayor tasa de F (-) que la uninodularidad (p = 0.0005). Edad, sexo, diámetro y método de obtención no fueron condicionantes para el resultado de la PAAF (P = NS). conclusión: En nuestra experiencia, los nódulos quísticos y la multinodularidad fueron los únicos factores de riesgo estadísticamente significativos. La condición quística es coincidente con la literatura. No encontramos justificación para la multinodularidad como factor de riesgo. Un sesgo considerado es la diversidad de citólogos que estudiaron las PAAF.


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360 cases of differentiated thyroid carcinoma: follow-up in a single institution

Assumpção LVM, Martelli V, Melo TGEndocrinology Division, Internal Medicine Department, State University of Campinas; Campinas, Brazil

Background: We aim to perform a retrospective study to assess 360 patients with differentiated thyroid carcinoma (DTC) who have been treated surgically, with radioiodine and TSH suppressive therapy since 1981 in a referral university center. Methods: Retrospective analysis of a cohort of thyroid cancer patients. Results: 280 patients had the diagnosis of papillary thyroid carcinoma (PTC) and 80 had follicular thyroid carcinoma (FTC). Concerning PTC, the female to male incidence rate was 4,8 and patients were 5 to 87 years old at the time of diagnosis. For FTC, female to male incidence rate was 5,6 and the age range was 8 to 76 years old. After surgery, 37,5% of patients with PTC and 6,2% of patients with FTC showed neck lymph nodes metastasis. After first whole body scan with 131-iodine, 12,8% of PTC patients and 36,2% of FTC patients evidenced distant metastasis, more frequently to lung and bones. Majority of patients were staged according to TNM1992 as stage I or II (79% of PTC, 61% of FTC). On follow-up, 6% of PTC patients presented with late distant metastasis, as well as 13,2% of FTC patients. All these metastasis were treated with radioiodine, surgery or radiotherapy, concerning each case accordingly with current guidelines. conclusion: Until now, we consider that 61,6% of PTC patients and 38,7% of FTC patients are under complete remission of the disease. 0,02% of PTC and 0,1% of FTC patients deceived from carcinoma complications. All other cases are on follow-up with metastasis under treatment or incomplete remission.

PO. 133

Frecuencia de nódulo tiroideo en el Valle de México

Hurtado-López LM, Zaldivar RR, Basurto KE, Pulido CA, Vázquez OR, Chapa AO, Etchegaray DA, MontesdeOca E, Martinez-Duncker CClínica de Tiroides, Hospital General de México; México DF

antecedentes: La frecuencia de nódulo tiroideo en la población abierta se considera de 4% a 7%, en nuestro país desconocemos la cifra real. objetivo: Del presente trabajo es conocer la frecuencia de nódulo tiroideo en el valle de México. Material y método: Estudio prospectivo, longitudinal, descriptivo, con muestra calculada a la población nacional incluyendo a 2400 sujetos sin enfermedad tiroidea conocida, evaluados por palpación, ultrasonido y determinación de TSH. Variables estudiadas: Género, evaluada presencia de nódulo tiroideo, diagnóstico por BAAF y/o histopatológico. Resultados: Mujeres 1966, Varones 434, la presencia de nódulo tiroideo por ultrasonido de menos de 1 cm fue de 24% la TSH se encontró normal en 72%, Bajo en 12% y alto en 16%, la presencia de nódulo tiroideo palpable fue de 34 casos (1.42%) con diagnostico bocio coloide nodular: 16 (47.2%), adenoma folicular: 8 (23.5%), tiroiditis Hashimoto: 7 (20.5%), carcinoma papilar: 2 (5.9%), adenoma Hurtle: 1 (2.9%). conclusión: La frecuencia de nódulo tiroideo en el valle de México es notablemente menor a lo reportado en el mundo.

PO. 134

Thyroid cancer I131 adyuvant treatment

Pacheco OL, Martínez JAHospital “Carlos Andrade Marín”; Quito, Ecuador

introduction: Although surgery is the mainstay of initial treatment of differentiated thyroid carcinoma, medical treatment plays an important role in the subsequent management of these patients. There have been relatively few studies about the influence on outcome of radioactive iodine (RAI) postoperative therapy in relation to other prognostic factors. We have retrospectively analysed the prognostic influence of RAI in a homogeneous series of patients surgically treated for well-differentiated thyroid carcinoma. Materials and methods: During 1980-1998, 114 consecutive patients with TNM stage I to stage III differentiated thyroid carcinoma underwent surgery at the Head and Neck Surgery Department of the Social Security Hospital in Quito, Ecuador. Fifty-six patients received therapeutic RAI and 59 did not. The following prognostic factors were compared in both groups: age, gender, histology (papillary or follicular) of the tumor, palpable lymph nodes, histology of the lymph nodes when dissected, TNM stage, extent of surgery and surgical margins. There were no statistically significant differences between both groups except for the type of surgery. There was a significant higher number of patients with partial thyroid surgery in the RAI-non treated group. Results: Local and regional recurrences were similar but distant metastases were less frequent in patients who received RAI. This difference was not, however, statistically significant (p: > 0.05). Overall 5- (100% versus 81%) and 10-year (100% versus 77%) survivals, estimated by the Kaplan-Meier method, were significantly better in RAI-treated group (p: 0.031). RAI improved significantly 5- and 10-year survivals in the total or near-total surgery group (p: 0.016) and also, but not significantly (p:0.094), in the stage II-III group. RAI treatment did not improve survival in the stage I and partial surgery groups. Finally, comparing RAI doses of 30 to 50 mCi (27 patients) with 51 to 100 mCi (29 patients), loco-regional recurrences, metastases as well as 5- and 10-year survivals were not different (p: > 0.05). conclusions: It seems that RAI is efficacious for patients with well-differentiated thyroid carcinoma confined to the neck, particularly for those treated with total or near-total thyrodectomy, and probably, only for stage II and III patients. No significant differences in tumor recurrence neither in survival with low or high doses of RAI were found.


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An altered expression of CCR3, CCR7 and CXCR4 in papillary thyroid cancer

González HE1, Leiva A4, Tobar H3, Böhmwald K4, Tapia K1, Kalergis AM2-3, Riedel CA4

¹Departamento de Cirugía Oncológica y ²Reumatología, Facultad de Medicina Pontificia Universidad Católica de Chile. ³Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile. 4Laboratorio de Biología Celular y Farmacología, Departamento de Ciencias Biológicas, Facultad de la Salud, Universidad Andrés Bello.

Papillary thyroid cancer (PTC), the most prevalent type of differentiated thyroid carcinoma, displays a strikingly high frequency of lymph node metastasis. Recent data suggest that chemokines can play an important role during tumor progression and metastatic migration of tumor cells. To determinate whether chemokine receptors contribute to the process of metastasis in PTC, we have assessed expression of these molecules in tumor and non-malignant thyroid tissues from patients suffering from PTC. Our data show a significant enhancement for CCR3, CCR7 and CXCR4 expression in PTC tissues, as determined by immunohistochemical staining and flow cytometric analyses. In addition, we observed that, while CCR3 and CXCR4 were present both in tumors and control thyroid tissues, expression of CCR7 was scarcely detected in PTC cells and not found in control cells. Our data is consistent with the notion that there is an altered expression of chemokine receptors in PTC and suggest that CCR3, CCR7 and CXCR4 could contribute to the development of thyroid cancer. Furthermore, these findings support that CCR3, CXCR4 and CCR7 as potentially useful markers for malignancy during PTC.


index of autHors

S220

aAbalovich M .................................. PO.025, PO.040Abelleira E ................................................... PO.065Acosta A ...................................................... PO.054Adam RL .......................................................OR.08Alamilla LL .................................................. PO.104Alamino VA .......................................OR.18, OR.20Alamino VA ................................................. PO.051Albieri CD ................................................... PO.106Alcaraz G ..................................................... PO.025Almeida NCP .............................................. PO.045Almiron R ................................................... PO.034Alves MLD .................................................. PO.007Amato AA .....................................................OR.13Andrade BM ................................................ PO.044Andrade JA .................................................. PO.118Andrade LJO ................................. PO.026, PO.027Andrade VA ................................................. PO.015Antonovic G ................................................ PO.003Antunes DE ................................................. PO.106Antunez PB ................................................. PO.067Araújo RL .................................................... PO.044Araujo-Filho VJF ......................................... PO.126Arias M ........................................................ PO.123Assis Brasil B ................................................ PO.070Assumpção LM ..............................................OR.08Assumpção LVM ............. PO.074, PO.096, PO.101,

PO.102, PO.132Assupção CB ............................................... PO.068Atta AM ...................................................... PO.026Atta AM ....................................................... PO.027Augusto GA ................................................ PO.117Azambuja Filho F ....................... PO.111, PO.113Azevedo GFM ............................................. PO.100Azevedo MF ....................................OR.13, PO.047Azi NM ....................................................... PO.098

BBacchini V ................................................... PO.128Balarini LD .................................................. PO.071Ballarini M ................................................... PO.029Bampa G ..................................................... PO.050Baptistella LC .............................................. PO.097Barberán M ................................................. PO.123Barella JLS ................................................... PO.118Barra GB .......................................................OR.13Barreiro Arcos ML ....................................... PO.048Barría M ...................................................... PO.129Barros CJV .................................... PO.001, PO.030

Barros RK .................................................... PO.035Barroso PF .................................................. PO.017Basurto KE .................................... PO.108, PO.133Batista AA ................................... PO.111, PO.113Beltrao CB ................................................... PO.002Bergoglio L ................................................. PO.099Beserra ICR ................................... PO.001, PO.030Bilhar FA ....................... PO.111, PO.112, PO.113Biscolla RPM .................................................OR.22Bittencourt AV .............................. PO.026, PO.027Bizeli R ........................................................ PO.077Bloise FF ..................................................... PO.006Bloise W ...................................................... PO.009Blumemberg S ............................................. PO.073Blummenberg S ........................................... PO.071Boero L ....................................................... PO.054Bogado L .................................................... PO.034Böhmwald K ................................................ PO.135 Bortoloni LGC ............................................ PO.089Braga WMO .................................. PO.058, PO.107Brantes S ..................................................... PO.129Brenta G ...................................................... PO.054Brites F ........................................................ PO.054Brunás O ..................................................... PO.131Bruneto EL ................................................. PO.052Brust ES ...................................................... PO.002Bueno FN .................................................... PO.106Buesco A ..................................................... PO.019Buescu A ......................... PO.078, PO.094, PO.095Bufalo NE ............ OR.15, OR.16, PO.032, PO.075

cCabezón CA ................................................ PO.072Calabrese MC .............................................. PO.025Calabrese MC .............................................. PO.040Caldas G ...................................................... PO.116Cale J .......................................................... PO.092Calil-Silveira J .............................................. PO.060Calvi SA ....................................................... PO.049Camargo RA ................................................ PO.028Camargo RRY ............................................. PO.004Camargo RY .................................. PO.117, PO.130Camargo RYA ................................ PO.119, PO.121Caminha LSC .............................................. PO.019Canani LH .................................................. PO.031Capp C ........................................................ PO.070Caracas N .................................................... PO.098Cardoso LC ........................ OR.12, OR.19, PO.020

Index of authors

S221

Cardoso-Demartini A .................................. PO.069Carrasco N ....................................................OR.04Carrizo C .................................................... PO.072Carvalho DP ........................OR.12, OR.19, PO.020,

PO.043, PO.044, PO.058, PO.078, PO.107Carvalho GA .....................OR.07, PO.077, PO.085,

PO.088, PO.089Carvalho GM .............................................. PO.068Carvalho LG ................................................ PO.017Carvalho LR ................................................ PO.014Carvalho TMO ..............................................OR.11Casal M ....................................................... PO.125Castaldi SA .................................................. PO.074Castro CLN ................................................. PO.011Castro LC ......................................................OR.13Cerutti JM ................................................... PO.124Chachamovitz DSO ....................... PO.011, PO.023Chagas AJ ........................................OR.21, PO.022Chammas MC ............................................. PO.002Chapa AO ..................................... PO.108, PO.133Chiganer G .................................................. PO.131Coelho SM .................................................. PO.078Corbo R ...................................................... PO.078Cordeiro A .................................................. PO.006Cordeiro MFN ............................................ PO.011Cordero F .................................................... PO.123Corino M .................................................... PO.128Corralo GCMB ............................................ PO.013Correa ARR ................................................. PO.021Corrêa da Costa VM .................................... PO.062Costa MEWF ............................................... PO.020Costa VMC ...................................................OR.12Cremaschi GA ............................................. PO.048Cremasco T ................................................. PO.071Crispim D .................................................... PO.031Croffi RV ..................................................... PO.053Cross G ....................................................... PO.065Cruz AD ..................................................... PO.110Cruz JB .........................................................OR.14Cunha LL ......................................................OR.06Cunha LL ...................................... PO.074, PO.075Cunha M ....................................... PO.013, PO.127Cury AN ..................................................... PO.032Cuvertino E ................................................. PO.099

Dda Cruz RP .................................................. PO.033da Cunha AB ............................................... PO.033

da Cunha AMF ............................................ PO.005da Silva MJ .................................... PO.057, PO.126Dagrosa A .................................................... PO.125Dare GLR .................................................... PO.046de Brito KRS ............................................... PO.033de Candia L ................................... PO.092, PO.131de Castro M ................................................ PO.046De Farias RF ................................................ PO.050De Paula EC .................................. PO.109, PO.110De Paula GM ............................................... PO.109De Paula HM .............................................. PO.109De Sibio MT ............................................... PO.045de Sousa PB ................................................. PO.008Denardi FC ................................................. PO.101Denardi FC ................................................. PO.102Dias EO ........................................ PO.028, PO.071Dias NH ...................................................... PO.014Dias V .............................................OR.21, PO.022Diaz AS ....................................................... PO.056Díaz R ......................................................... PO.086Dios A ......................................................... PO.084Dominguez Fonseca CB ................................OR.23Dora JM ........................................ PO.015, PO.039Drnovsek M ................................................ PO.003Duarte GC .................................................. PO.007

eEl Husny AS ................................................ PO.021Elias N ......................................................... PO.040Ercolano M ................................................. PO.003Estivalet A .....................................................OR.05Estivalet AAF ............................................... PO.031Etchebehere ECSC ...................................... PO.096Etchegaray DA ............................................ PO.108Etchegaray DA ............................................ PO.133

fFalcón-de-Legal E ........... PO.012, PO.034, PO.091Faraj G ........................................................ PO.081Faria CP ...................................................... PO.100Farías P ........................................................ PO.093Farías RN .................................................... PO.048Faure E ............................ PO.081, PO.092, PO.093Faustino LC ...................................................OR.11Favero DM .................................................. PO.049Fernandes ARGC ......................................... PO.106Fernandes LPS .................................OR.14, PO.018Fernandes-Caldato MC .................. PO.021, PO.068Fernandez M ............................................... PO.120

Index of authors

S222

Ferraz A ...................................................... PO.117Ferreira ACF ....................... OR.12, OR.19, PO.058Ferreira AO ................................................. PO.021Ferreira MA ................................................. PO.004Ferreira RC ....................................................OR.08Fideleff H .................................................... PO.105Figari M ...................................................... PO.093Fiore APZP ...................................................OR.01Flores-Rebollar A ............. PO.010, PO.079, PO.080Fortunato RS ............................................... PO.043Fozzatti L .................................................... PO.055França LS .................................................... PO.027Franco C ..................................................... PO.115Frankenfeld TGP ......................................... PO.043Frascaroli G ................................................. PO.105Freitas LV .................................................... PO.071Freitas ML .........................................OR.12, OR.19Freitas MMW .............................................. PO.029Friguglietti CU ............................................ PO.126Frota D ....................................................... PO.073Fuentes A .................................................... PO.003Fuziwara C ....................................................OR.03Fuziwara CS .................................. PO.057, PO.126

gGalindo RME .............................................. PO.104Galrão AL .................................................... PO.004Gatti G ........................................................ PO.038Gauna A ........................................ PO.003, PO.076Gehard R ..................................................... PO.117Genaro AM ................................................. PO.048Genoni V ..................................................... PO.087Geres A ....................................................... PO.099Ginabreda MGP ................. OR.12, OR.19, PO.058Glikman P ................................................... PO.084Godoy P ........................................................OR.13Goemann IM ...................................OR.17, PO.059Góis C ......................................................... PO.073Gomes AS .................................................... PO.004Gomes EMS .................................. PO.094, PO.095Gómez V ..................................................... PO.080Gonçalves CFL ............................................ PO.058Gonçalves ICG ............................................ PO.113Gonçalves ICR ..........................................PO.111Gonçalves SR .................................................OR.03González Garcia M ...................................... PO.131González HE ............................................... PO.135 González N ................................................. PO.064González-Treviño O ........ PO.010, PO.079, PO.080

Goulart-Silva F ..............................................OR.02Graf H .................OR.07, PO.069, PO.077, PO.085,

PO.088, PO.089Guedes DSN ............................................... PO.005Guilhem MS ..................................................OR.15Guilhen ACT ...................... OR.06, OR.08, PO.075Guillén C ..................................................... PO.076Guimarães MM .............................. PO.001, PO.030Gutierrez S .................................... PO.025, PO.040

hHanaoka N .................................................. PO.118Harney JW .................................................. PO.059Haseitel M ..................................... PO.065, PO.129Hidalgo ....................................................... PO.041Hidalgo S .................................................... PO.114Higa AM ..................................................... PO.063Hurtado-Lopez LM ...........OR.23, PO.108, PO.133

iIgnacio DL .................................................. PO.043Imbroise R .................................... PO.001, PO.030Iturbe B ....................................................... PO.099

jJahn G ......................................................... PO.120Jara J ........................................................... PO.064Jatene EM ................................................... PO.106Jerusalmi ALC ............................................. PO.011Jesus R ........................................................ PO.073Jorge EN .......................................................OR.14Juarez XE ...................................... PO.056, PO.103Juliano AG .................................................. PO.002Juvenal G ...........PO.081, PO.092, PO.120, PO.125Juvenal GJ ................................................... PO.083

kKalergis AM ................................................. PO.135 Kanamura CT .............................................. PO.004Kasamatsu T ....................................OR.24, PO.037Kaskus L ...................................................... PO.073Kaskus LE ................................................... PO.071Kimura ET ........... OR.01, OR.03, PO.057, PO.126Klecha AJ .................................................... PO.048Knobel M ............OR.21, PO.004, PO.022, PO.028,

PO.035, PO.117, PO.119, PO.121, PO.130Kruschewsky LS ........................................... PO.098Kulcsar MA .................................................. PO.126

Index of authors

S223

lLacerda L .................................................... PO.069Laguna J ...................................................... PO.003Lambertini R ............................................... PO.093Lamounier Filho A ...................................... PO.029Lapate RL .................................................... PO.014Larsen PR .................................................... PO.059Latini FRM .................................................. PO.124Lauand TCG ............................................... PO.008Lauand TGC ................................. PO.090, PO.100Laudi R ....................................................... PO.087Leiria LB ....................................... PO.031, PO.039Leite JL .............................................OR.15, OR.16Leite NJ ........................................................OR.08Leiva A ........................................................ PO.135 Leoni SG ..................................................... PO.057Lessa B ........................................................ PO.098Liberman C ................................................. PO.123Licht SD ...................................................... PO.067Lima AC ........................................................OR.11Lima EU ..................................................... PO.035Lima MCL .................................................. PO.096Lioi X ............................................ PO.114, PO.115Logullo AF .................................................. PO.126Longui CA .................................................. PO.032López-Carrasco G ............ PO.010, PO.079, PO.080Loureiro C .................................................. PO.029Lowenstein A ................................. PO.084, PO.087Lucero AM .................................................. PO.055Ludwig VB .................................... PO.085, PO.089Lutfi R ......................................................... PO.092Lutfi RJ ....................................................... PO.081Luvizotto RAM ............................. PO.045, PO.049

MMaccioni M ................................................. PO.038Machado UF ...................................OR.10, PO.053Machado WE ............................................... PO.015Maciel LMZ .................... PO.016, PO.042, PO.046Maciel RMB ....................... OR.22, OR.24, PO.037Magalhães PKR ............... PO.016, PO.042, PO.046Mahler G ..................................................... PO.099Maia AL ............... OR.05, OR.17, PO.015, PO.031,

PO.039, PO.059, PO.070, PO.082Malouf EZ ................................................... PO.013Mansur V .................................................... PO.073Marcello MA ...................................OR.06, PO.074Marino J ........................................ PO.045, PO.049Marone MS ...................................................OR.22

Marques ELV .............................................. PO.008Martelli V .................................................... PO.132Martin RM .................................................. PO.028Martínez JA ................................................. PO.134Martinez-Duncker C ................................... PO.133Martins Filho R ........................................... PO.096Martins RHG .............................................. PO.014Marui S ........................... PO.002, PO.035, PO.117Mascanfroni I ....................................OR.09, OR.18Mascanfroni ID .................OR.20, PO.051, PO.061Masini-Repiso AM ................ OR.04, OR.09, OR.18,

OR.20, PO.038, PO.051, PO.055, PO.061, PO.122

Matos PS .........................................OR.08, PO.096Matsumura L ...................................OR.24, PO.037Mazeto GMFS ...................OR.14, PO.014, PO.036Medeiros-Neto G ........................... OR. 21, PO.004,

PO.022, PO.130Meira DM ................................................... PO.033Melchor-Ruan J ........................................... PO.108Mello-Coelho V ........................................... PO.006Melo APM ................................................... PO.106Melo GM .................................................... PO.097Melo TG ......................... PO.101, PO.102, PO.132Mendes ALM .............................................. PO.023Mendes T .................................................... PO.071Mendes-Correa MC ..................................... PO.035Mendonça KT ............................................. PO.062Menoni-de-Lezcano M ................................ PO.012Meotti C .......................................................OR.05Mereshian P ................................................. PO.099Mesa Jr C ............OR.07, PO.069, PO.085, PO.088Metze K ........................................................OR.08Meurer L ..................................................... PO.070Meyer ELS .................................................. PO.039Mezalira PR ................................................. PO.022Miasaki FY ................................................... PO.085Migliano M ................................................. PO.128Mimura LY .................................................. PO.009Miranda D ................................................... PO.028Missaka RFBG ............................................. PO.036Molinari AS ................................ PO.111, PO.113Moloeznik L ................................................ PO.131Montaño-Lechuga MC ................................ PO.010Monte L ........................................ PO.119, PO.121Monte O ..................................................... PO.032Monteiro CD .............................................. PO.110Monteiro SHV ............................... PO.001, PO.030MontesdeOca E ..........................PO.108, E PO.133

Index of authors

S224

Montesinos MM ................. OR.18, OR.20, PO.051Mora HS ..................................................... PO.104Morari EC .........................................OR.06, OR.08Morari EC ................................................... PO.075Morelli S ...................................................... PO.128Moreno A .................................................... PO.128Moreno-Castañeda L ....... PO.010, PO.079, PO.080Moss M ....................................................... PO.003Moura J ....................................................... PO.009Moura M ..................................................... PO.089Moura-Neto A ............................... PO.101, PO.102Mousovich Neto F ....................................... PO.062Muniz TZ .................................................... PO.018Munizaga C ................................... PO.114, PO.115Munizaga F ..................... PO.041, PO.114, PO.115

nNaliato ER ................................................... PO.029Nascimento AF ............................................ PO.045Natera-Cruz E ............................................. PO.010Navarro AM ................................................ PO.007Navarro-Lara A .............................. PO.010, PO.080Naves LA .......................................................OR.13Nazar M ..............OR.09, PO.055, PO.061, PO.122Nebel E ....................................................... PO.131Nesi S .......................................................... PO.069Neves FAR ........................OR.13, PO.047, PO.050Neves SC .........................................OR.21, PO.022Nicola JP ................ OR.04, OR.09, OR.18, PO.038,

PO.055, PO.061, PO.122Nicolau W ................................................... PO.009Niepomniszcze H .......................... PO.065, PO.066Nogueira CR .......OR.14, PO.036, PO.045, PO.049Novelli JL ...................................... PO.092, PO.131Nunes MT ...........................OR.02, OR.10, PO.024,

PO.052, PO.053, PO.060Nuñez S ...................................................... PO.065

oOdawara AF ................................................ PO.118Oglio R ......................................... PO.083, PO.120Olguín M .................................................... PO.131Olimpio RMC ............................... PO.045, PO.049Oliveira AS .................................................. PO.047Oliveira FP .................................................. PO.023Oliveira JC ..................................... PO.109, PO.110Oliveira Jr SA ............................................... PO.049Oliveira LRC ............................................... PO.049

Oliveira RA .................................................. PO.019Oliveira RG ................................................. PO.068Olstein G ..................................................... PO.087Orlandi A .................................................... PO.105Otero J ........................................................ PO.025Ourdakian MK ............................................ PO.018Ovelar EC ................................................... PO.064

PPacheco OL ................................................. PO.134Padilha M .................................................... PO.116Padin R ....................................................... PO.128Padovani CR ..................................................OR.14Padovani RP ..................................................OR.22Padrón AS ................................................... PO.044Pagotto R ...................................... PO.120, PO.125Panernari T .................................................. PO.073Panico ALBG .............................................. PO.017Pantaleão TU ....................OR.12, PO.044, PO.062Parana R ........................................ PO.026, PO.027Pardo V ....................................................... PO.004Paula SLFM ................................................. PO.106Pazos-Moura C ............................................ PO.006Pedrosa HC ..................... PO.008, PO.090, PO.100Pedruzzi PAG .............................................. PO.088Pellizas CG ........... OR.18, OR.20, PO.051, PO.055,

PO.061, PO.122Penatti HC .................................................. PO.036Perez A ........................................................ PO.005Perez CLS ...........OR.07, PO.077, PO.088, PO.089Perona M .................................................... PO.125Pignataro O ................................... PO.120, PO.125Pinho J ........................................................ PO.116Pires RM .......................................................OR.11Pisarev M ....................................... PO.120, PO.125Pisarev MA .................................................. PO.083Pitoia F .......................................... PO.065, PO.066Pivotto DR ....................................................OR.14Polikarpov I ................................................. PO.050Possato RF .................................................. PO.004Possato-Fernandes R .................................... PO.130Poyares LL ....................................................OR.10Prado Jr LM ................................................ PO.090Pretell EA ...................................... PO.063, PO.064Pulido CA ..................................... PO.108, PO.133Puñales MK ...................................................OR.05Puscar A ...................................................... PO.105Pusiol E ....................................................... PO.066

Index of authors

S225

QQuerino AL ................................................. PO.020Quiroga S .................................................... PO.131

RRabinovich GA .......OR.18, GA OR.20, GA PO.051Raimundo SG ............................ OR.01, SG PO.057Ramos C P ......................................................O.129Ramos CD ................................................... PO.096Ramos HE ................................................... PO.088Ramos M ..................................................... PO.091Razzolini L ................................. PO.111, PO.113Rebelo E ..................................................... PO.019Redondo J ................................................... PO.064Reis AAS ..................................................... PO.110Renaux L ....................................... PO.071, PO.073Reyes A ......................................... PO.084, PO.087Rezende E .....................................................OR.03Rezzónico JN .............................................. PO.066Rezzónico M ............................................... PO.066Ribeiro ICJ .................................................. PO.050Ribeiro MG ................................... PO.001, PO.030Ricarte-Filho JC .......................................... PO.057Ricarte-Filho JCM .........................................OR.01Riedel CA .................................................... PO.135 Rocha AP ......................................................OR.05Romaldini JH ......................OR.15, OR.16, PO.013,

PO.118, PO.127Romano RM ................................................ PO.024Romero N ................................................... PO.099Rosenthal D ................................................ PO.062Rossi R ........................................................ PO.115Rubio GS ......................................................OR.21Rubio IGS ....................... PO.004, PO.022, PO.130Ruiz-Juvera A ........... PO.010, A PO.079, A PO.080Rumjanek V ................................................. PO.006

sSá MBR ....................................................... PO.127Sacramento Monte RS ................................. PO.005Saddi VA ..................................................... PO.110Saldanha F ................................................... PO.029Salgado RM ................................................. PO.024Salvai ME .................................................... PO.065Santana CM ..................... PO.008, PO.090, PO.100Santisteban P ............................................... PO.020Santoro S ..................................................... PO.087Santos AGA ................................................. PO.090Santos AO ................................................... PO.096

Santos JB ..................................................... PO.071Santos JG .................................................... PO.071Santos KTP .................................................. PO.014Santos MCS ................................... PO.058, PO.107Santos RB ............. OR.15, OR.16, PO.013, PO.118,

PO.127Santos RRA ................................................. PO.098Sapienza MT ............................................... PO.002Sasson P ........................................ PO.071, PO.073Scalissi NM .................................................. PO.032Schwarsztein D ............................................ PO.092Seoane LA ..................................... PO.119, PO.121Sepúlveda-Méndez J ........ PO.010, PO.079, PO.080Sequera A .................................................... PO.105Serrano-Nascimento C ........ OR.02, OR.10, PO.060Sgarbi JA .........................................OR.24, PO.037Sguillar DA .................................................. PO.097Shiang C ...................................................... PO.117Sibio MT ..................................................... PO.049Silva ACN ......................................................OR.15Silva Croome M ........................................... PO.076Silva Croome MC ........................................ PO.003Silva DM ..................................................... PO.110Silva EC ....................................................... PO.109Silva GB ...................................................... PO.071Silva JR .......................................................... OR.08Silvares MRC ............................................... PO.036Silveira EC ................................................... PO.021Simeoni LA ................................................. PO.047Simkin D ..................................................... PO.093Siqueira D ................................................... PO.070Siqueira DR ...................................................OR.05Soares DV ................................................... PO.005Soares F .........................................................OR.08Soares FA ........................................OR.06, PO.075Sosa CA ....................................................... PO.104Sousa MSA .................................................. PO.124Sousa PAM .................................................. PO.019Sousa PB ..................................................... PO.100Soutelo MJ .................................................. PO.081Souza ECL .................................... PO.058, PO.107Souza PB ....................................... PO.052, PO.090Souza RAS ................................................... PO.097Sterle HA .................................................... PO.048Stivel M ....................................................... PO.025Susperreguy S .........OR.04, OR.18, OR.20, PO.051Sutton M ..................................................... PO.054Sztal-Mazer S .............................................. PO.069

Index of authors

S226

tTapia K ........................................................ PO.135 Teixeira PFS ..................... PO.011, PO.017, PO.023Teixeira SS .......................................OR.10, PO.053Thierer J ...................................................... PO.054Thomasz L .................................... PO.083, PO.120Thomaz LPM .............................................. PO.033Tobar H ...................................................... PO.135 Togashi M ................................................... PO.050Tomimori E ................................................. PO.117Tomimori EK .................. PO.007, PO.028, PO.119,

PO.121, PO.130Toro D ........................................................ PO.120Tricolli R ..................................................... PO.098Trippia M ......................................................OR.07

VVainstein N .................................................. PO.054Vaisman F .................................................... PO.078Vaisman M ....................... PO.011, PO.017, PO.019,

PO.023, PO.029, PO.078, PO.094, PO.095

Valles V ....................................................... PO.080Vassallo J ............................ OR.06, PO.075, OR.08Vázquez OR .................................. PO.108, PO.133Velasco LFR ..................................................OR.13Velázquez CFJ ............................................. PO.104Velazquez-Fernandez D .................................OR.23Velez ML ....................................... PO.055, PO.122Veliz J .......................................................... PO.129Viale F ........................................... PO.003, PO.084Viale Fanny .................................................. PO.076

Viana M ..........................................OR.21, PO.022Viégas MA ................................................... PO.116Vieira JGH .................................................... OR.22Vigário PS ..................................... PO.011, PO.023Viggiano DPPO .......................................... PO.106Villagelin D ..................... PO.013, PO.118, PO.127Villamar S .................................................... PO.120Villar A ........................................................ PO.093Villegas P ..................................................... PO.129Violante AHD ............................................. PO.029Vos XG ..........................................................OR.16

WWajner SM ......................... OR.17, PO.070, PO.082Ward L ........................................................ PO.096Ward LS ...................OR.06, OR.08, OR.15, OR.16,

PO.032, PO.074, PO.075Watanabe T ................................................. PO.002Wesley SRAG ............................................... PO.089Wiersinga WM ...............................................OR.16Wohllk N ....................................... PO.086, PO.129

yYamashita AS .................................................OR.03Yoon HS ...................................................... PO.126

zZaldivar RR ................................... PO.108, PO.133Zambrini H ................................................. PO.035Zarza Z ....................................................... PO.064Zennig N ..................................................... PO.082

Index of authors

inpi-deinp/df prot. 000307-04 issn 0004-2730 ...¡ucia carneiro universidade federal de são paulo...

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