Thyroid nodules and differentiated thyroid cancer: Brazilian consensus

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.Os nódulos tireoidianos constituem a principal manifestação clínica de uma série de doenças da tireóide com uma prevalência de aproximadamente 10% na população adulta. O maior desafio é excluir o câncer da tireóide, que ocorre em 5 a 10% dos casos. Os carcinomas diferenciados respondem por 90% dos casos de todas as neoplasias malignas da tireóide. A maioria dos pacientes com carcinoma diferenciado apresenta, geralmente, um bom prognóstico quando tratada adequadamente, com índices de mortalidade similares à população geral. No entanto, alguns indivíduos apresentam doença agressiva, desafiando o conhecimento atual e ilustrando a complexidade do manejo dessa neoplasia. No presente trabalho, reunimos 8 membros do Departamento de Tireóide da Sociedade Brasileira de Endocrinologia & Metabologia, para elaborarmos, por consenso, as diretrizes brasileiras no manejo dos nódulos tireoidianos e do câncer diferenciado da tireóide. Os membros participantes representam diferentes Centros Universitários do Brasil, refletindo diferentes abordagens diagnósticas e terapêuticas. Inicialmente, cada participante ficou responsável pela redação de determinado tema a ser enviado ao Coordenador, que, após revisão editorial e elaboração da primeira versão do manuscrito, enviou ao grupo para sugestões e aperfeiçoamentos. Quando concluído, o manuscrito foi novamente enviado e revisado por todos. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão pertinente da literatura.Sociedade Brasileira de Endocrinologia e Metabologia Departamento de TireóideUniversidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto Alegre Serviço de EndocrinologiaUNICAMP Faculdade de Ciências Médicas Departamento de Clínica MédicaUniversidade Federal do Paraná Serviço de Endocrinologia e MetabologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica MédicaSanta Casa de Belo Horizonte Serviço de Endocrinologia Departamento de TireóideUniversidade Federal do Rio de Janeiro Faculdade de Medicina Hospital Universitário Clementino Fraga FilhoUNIFESP, EPM, Depto. de MedicinaSciEL

Nódulo tireoidiano e câncer diferenciado de tireoide: atualização do consenso brasileiro

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.Nódulos tireoidianos são muito frequentes, sobretudo quando se empregam métodos sensíveis de imagem. Embora o câncer seja proporcionalmente raro, sua incidência vem aumentando, especialmente de tumores pequenos, cuja evolução clínica é incerta. A maioria dos pacientes com carcinoma diferenciado de tireoide evolui bem quando adequadamente tratada, com índices de mortalidade similares à população geral. Por outro lado, um percentual não desprezível apresenta recidivas e alguns eventualmente não respondem às terapias convencionais, evoluindo para óbito. Assim, o desafio é distinguir os pacientes merecedores de condutas mais agressivas e, ao mesmo tempo e não menos importante, poupar a maioria de tratamentos e procedimentos desnecessários. Atualizamos o Consenso Brasileiro publicado em 2007, ressaltando os avanços diagnósticos e terapêuticos que os participantes, de diferentes Centros Universitários do Brasil, consideram mais relevantes para prática clínica. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão da literatura pertinente.Instituto de Ensino e Pesquisa Serviço de EndocrinologiaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Clínica MédicaUniversidade Federal do Paraná Serviço de Endocrinologia e MetabologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de Clínica MédicaUniversidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto Alegre Serviço de EndocrinologiaUniversidade Federal do Rio de Janeiro Faculdade de Medicina Hospital Universitário Clementino Fraga FilhoUNIFESP, EPM, Depto. de MedicinaSciEL

Thyroid nodules and differentiated thyroid cancer: Brazilian consensus

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.Os nódulos tireoidianos constituem a principal manifestação clínica de uma série de doenças da tireóide com uma prevalência de aproximadamente 10% na população adulta. O maior desafio é excluir o câncer da tireóide, que ocorre em 5 a 10% dos casos. Os carcinomas diferenciados respondem por 90% dos casos de todas as neoplasias malignas da tireóide. A maioria dos pacientes com carcinoma diferenciado apresenta, geralmente, um bom prognóstico quando tratada adequadamente, com índices de mortalidade similares à população geral. No entanto, alguns indivíduos apresentam doença agressiva, desafiando o conhecimento atual e ilustrando a complexidade do manejo dessa neoplasia. No presente trabalho, reunimos 8 membros do Departamento de Tireóide da Sociedade Brasileira de Endocrinologia & Metabologia, para elaborarmos, por consenso, as diretrizes brasileiras no manejo dos nódulos tireoidianos e do câncer diferenciado da tireóide. Os membros participantes representam diferentes Centros Universitários do Brasil, refletindo diferentes abordagens diagnósticas e terapêuticas. Inicialmente, cada participante ficou responsável pela redação de determinado tema a ser enviado ao Coordenador, que, após revisão editorial e elaboração da primeira versão do manuscrito, enviou ao grupo para sugestões e aperfeiçoamentos. Quando concluído, o manuscrito foi novamente enviado e revisado por todos. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão pertinente da literatura.86789

Nódulo tireoidiano e câncer diferenciado de tireoide: atualização do consenso brasileiro

Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.Nódulos tireoidianos são muito frequentes, sobretudo quando se empregam métodos sensíveis de imagem. Embora o câncer seja proporcionalmente raro, sua incidência vem aumentando, especialmente de tumores pequenos, cuja evolução clínica é incerta. A maioria dos pacientes com carcinoma diferenciado de tireoide evolui bem quando adequadamente tratada, com índices de mortalidade similares à população geral. Por outro lado, um percentual não desprezível apresenta recidivas e alguns eventualmente não respondem às terapias convencionais, evoluindo para óbito. Assim, o desafio é distinguir os pacientes merecedores de condutas mais agressivas e, ao mesmo tempo e não menos importante, poupar a maioria de tratamentos e procedimentos desnecessários. Atualizamos o Consenso Brasileiro publicado em 2007, ressaltando os avanços diagnósticos e terapêuticos que os participantes, de diferentes Centros Universitários do Brasil, consideram mais relevantes para prática clínica. A elaboração dessas diretrizes foi baseada na experiência dos participantes e revisão da literatura pertinente.24026

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazili an centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome83289298CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DO RIO GRANDE DO SUL - FAPERGSSem informaçãoSem informação2006/60402-1; 2010/51547-1; 2013/01476-9; 2014/06570-6; 2009/50575-4; 2010/51546-5; 2012/21942-116/2551-0000482-

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome

Complete Thyroxine-Binding Globulin (TBG) Deficiency Produced by a Mutation in Acceptor Splice Site Causing Frameshift and Early Termination of Translation (TBG-Kankakee)12

Fourteen T4-binding globulin (TBG) variants have been identified at the gene level. They are all located in the coding region of the gene and 6 produce complete deficiency of TBG (TBG-CD). We now describe the first mutation in a noncoding region producing TBG-CD. The proband was treated for over 20 yr with L-T4 because of fatigue associated with a low concentration of serum total T4. Fifteen family members were studied showing low total T4 inherited as an X chromosome-linked trait, and affected males had undetectable TBG in serum. Sequencing of the entire coding region and promoter of the TBG gene revealed no abnormality. However, an A to G transition was found in the acceptor splice junction of intron II that produced a new HaeIII restriction site cosegregating with the TBG-CD phenotype. Sequencing exon 1 to exon 3 of TBG complementary DNA reverse transcribed from messenger RNA of skin fibroblasts from an affected male, confirmed a shift in the ag acceptor splice site. This results in the insertion of a G in exon 2 and causes a frameshift and a premature stop at codon 195. This early termination of translation predicts a truncated TBG lacking 201 amino acids