Recomendações da Sociedade Latino-Americana de Tireoide para diagnóstico e manejo do carcinoma diferenciado de tireoide

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries.Estas recomendações tiveram por objetivo o desenvolvimento de diretrizes para avaliação e manejo de pacientes com câncer diferenciado da tiroide em países latino-americanos. Um painel composto por 13 membros da Sociedade Latino-Americana de Tireoide (SLAT) - que estavam envolvidos em pesquisas, e eram peritos no cuidado do paciente com câncer da tiroide e provenientes de diferentes centros médicos latino-americanos - utilizou os princípios da Medicina Baseada em Evidências para produzir esse consenso. Após uma primeira reunião, um texto inicial foi elaborado, baseado em evidências e opiniões dos especialistas do painel e, posteriormente, circulado entre os membros do painel, para revisão. Após a revisão, o documento foi enviado aos membros da SLAT para comentários e considerações e, finalmente, revisado e refinado pelos autores. As recomendações finais aqui apresentadas demonstram o estado da arte no manejo do câncer diferenciado da tireoide aplicadas aos países latino-americanos.88488

Recomendações da Sociedade Latino-Americana de Tireoide no manejo de nódulos tireoideos

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries.Vários consensos têm sido publicados acerca do diagnóstico e do tratamento de nódulos e câncer da tireoide. Entretanto, as recentes recomendações nem sempre são apropriadas para diferentes regiões ou países. O objetivo deste trabalho foi oferecer uma série de recomendações para a avaliação e conduta de pacientes portadores de nódulos tireoideos aplicáveis a todos os países da América Latina. O trabalho foi realizado por um comitê composto por 13 membros da Sociedade Latino-Americana de Tireoide envolvidos com pesquisa e manejo de pacientes portadores de nódulos e carcinoma diferenciado da tireoide, de diferentes centros médicos da América Latina. As recomendações foram estabelecidas, após consenso, utilizando as opiniões especializadas de cada membro e os princípios da medicina baseada em evidência. Após a primeira reunião do grupo, um primeiro documento foi elaborado e encaminhado a todos os membros para revisão. Posteriormente, o documento foi enviado aos membros da Sociedade Latino-Americana de Tireoide para avaliação, sugestões e comentários. A versão final, elaborada após refinada revisão de todos os autores, representa o estado da arte no diagnóstico e na conduta de nódulos tireoideos, aplicáveis a todos os países da América Latina

Recomendações da sociedade Latino-Americana de tireoide no manejo de nódulos tireoideos

Several guidelines on diagnosis and treatment of thyroid nodules and cancer have recently been published. However, recommended practices are not always appropriate to different settings or countries. The aim of this consensus was to develop Clinical Guidelines for evaluation and management of patients with thyroid nodules applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society involved with research and management of thyroid nodules and cancer from different medical centers in Latin America. The consensus was produced based on the expert opinion of the panel with use of principles of evidence-based medicine. Following a group meeting, a first draft based on the expert opinion of the panel was elaborated and later circulated among panel members for further revision. After revision, this document was submitted to all LATS members for commentaries and considerations and finally revised and refined by the authors. The final recommendations represent state of the art on management of thyroid nodules applied to all Latin American countries539Vários consensos têm sido publicados acerca do diagnóstico e do tratamento de nódulos e câncer da tireoide. Entretanto, as recentes recomendações nem sempre são apropriadas para diferentes regiões ou países. O objetivo deste trabalho foi oferecer uma série de recomendações para a avaliação e conduta de pacientes portadores de nódulos tireoideos aplicáveis a todos os países da América Latina. O trabalho foi realizado por um comitê composto por 13 membros da Sociedade Latino-Americana de Tireoide envolvidos com pesquisa e manejo de pacientes portadores de nódulos e carcinoma diferenciado da tireoide, de diferentes centros médicos da América Latina. As recomendações foram estabelecidas, após consenso, utilizando as opiniões especializadas de cada membro e os princípios da medicina baseada em evidência. Após a primeira reunião do grupo, um primeiro documento foi elaborado e encaminhado a todos os membros para revisão. Posteriormente, o documento foi enviado aos membros da Sociedade Latino-Americana de Tireoide para avaliação, sugestões e comentários. A versão final, elaborada após refinada revisão de todos os autores, representa o estado da arte no diagnóstico e na conduta de nódulos tireoideos, aplicáveis a todos os países da América Latin

Expressão de proteínas SMAD, mediadores da sinalização de TGF-beta/activina, em tecidos de tiroide humana

OBJECTIVE: To investigate the expression of SMAD proteins in human thyroid tissues since the inactivation of TGF-β/activin signaling components is reported in several types of cancer. Phosphorylated SMAD 2 and SMAD3 (pSMAD2/3) associated with the SMAD4 induce the signal transduction generated by TGF-β and activin, while SMAD7 inhibits this intracellular signaling. Although TGF-β and activin exert antiproliferative roles in thyroid follicular cells, thyroid tumors express high levels of these proteins. MATERIALS AND METHODS: The protein expression of SMADs was evaluated in multinodular goiter, follicular adenoma, papillary and follicular carcinomas by immunohistochemistry. RESULTS: The expression of pSMAD2/3, SMAD4 and SMAD7 was observed in both benign and malignant thyroid tumors. Although pSMAD2/3, SMAD4 and SMAD7 exhibited high cytoplasmic staining in carcinomas, the nuclear staining of pSMAD2/3 was not different between benign and malignant lesions. CONCLUSIONS: The finding of SMADs expression in thyroid cells and the presence of pSMAD2/3 and SMAD4 proteins in the nucleus of tumor cells indicates propagation of TGF-β/activin signaling. However, the high expression of the inhibitory SMAD7, mostly in malignant tumors, could contribute to the attenuation of the SMADs antiproliferative signaling in thyroid carcinomas.OBJETIVO: Investigar a expressão de proteínas SMAD em tecidos de tiroide humana desde que a inativação dos componentes da sinalização de TGF-β/activina é relatada em diversos tipos de câncer. SMAD 2 e SMAD3 fosforilados (pSMAD2/3) associados com SMAD4 induzem a transmissão do sinal gerado por TGF-β e activina, enquanto SMAD7 inibe essa sinalização intracelular. Embora TGF-β e activina exerçam efeitos antiproliferativos nas células foliculares da tiroide, tumores de tiroide expressam altos níveis dessas proteínas. MATERIAIS E MÉTODOS: A expressão proteica de SMADs foi avaliada em bócio multinodular, adenoma folicular, carcinomas papilífero e folicular por imuno-histoquímica. RESULTADOS: A expressão de pSMAD2/3, SMAD4 e SMAD7 foi observada tanto em tumores benignos como malignos da tiroide. Embora pSMAD2/3, SMAD4 e SMAD7 exibissem alta positividade citoplasmática em carcinomas, a positividade nuclear de pSMAD2/3 não foi diferente entre lesões benignas e malignas da tiroide. CONCLUSÕES: O achado da expressão de SMADs em células tiroidianas e a presença das proteínas pSMAD2/3 e SMAD4 no núcleo de células tumorais indicam propagação da sinalização TGF-β/activina. Contudo, a alta expressão de SMAD7 inibitório, principalmente em tumores malignos, poderia contribuir para atenuação da sinalização antiproliferativa de SMADs em carcinomas de tiroide.(FAPESP) São Paulo Research Foundation(CAPES) Coordination for the Improvement of Higher Education PersonnelCNPq National Counsel of Technological and Scientific Developmen

Histopathological Characterization and Whole Exome Sequencing of Ectopic Thyroid: Fetal Architecture in a Functional Ectopic Gland from Adult Patient

Ectopic thyroid results from a migration defect of the developing gland during embryogenesis causing congenital hypothyroidism. But it has also been detected in asymptomatic individuals. This study aimed to investigate the histopathological, functional, and genetic features of human ectopic thyroids. Six samples were histologically examined, and the expression of the specific thyroid proteins was assessed by immunohistochemistry. Two samples were submitted to whole exome sequencing. An oropharynx sample showed immature fetal architecture tissue with clusters or cords of oval thyrocytes and small folliclesone sample exhibited a normal thyroid pattern while four showed colloid goiter. All ectopic thyroids expressed the specific thyroid genes and T4 at similar locations to those observed in normal thyroid. No somatic mutations associated with ectopic thyroid were found. This is the first immature thyroid fetal tissue observed in an ectopic thyroid due to the arrest of structural differentiation early in the colloid stage of development that proved able to synthesize thyroid hormone but not to respond to TSH. Despite the ability of all ectopic thyroids to synthetize specific thyroid proteins and T4, at some point in life, it may be insufficient to support body growth leading to hypothyroidism, as observed in some of the patients.FAPESP Grant [2009/53840-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, Brazil [2010/12005-9, 2014/24549-4]Instituto da TiroideUniv Sao Paulo FMUSP, Fac Med, Cellular & Mol Endocrine Lab, Thyroid Unit,LIM 25, Ave Doutor Arnaldo 455, BR-01246904 Sao Paulo, SP, BrazilSao Paulo Publ Hlth Serv, Adolfo Lutz Inst, Av Dr Arnaldo 355, BR-01246000 Sao Paulo, SP, BrazilHead & Neck Surg Santa Catarina Hosp, Av Paulista 200, BR-01310000 Sao Paulo, SP, BrazilUNESP, Botucatu Sch Med, Dept Internal Med, Av Prof Montenegro,S-N Dist Rubiao Jr, BR-18618687 Botucatu, SP, BrazilHosp Pediat Dr Juan Garrahan, Serv Endocrinol, Combate Pozos 1881,C1245AAM, Buenos Aires, DF, ArgentinaUniv Estadual Campinas, Fac Ciencias Med, Dept Cirurgia, Disciplina Cirurgia Cabeca & Pescoco, R Tessalia Vieira Camargo 126, BR-13083887 Campinas, SP, BrazilUniv Fortaleza Unifor, Med Sch, Av Washington Soares 1321, BR-60811905 Fortaleza, CE, BrazilUniv Fed Sao Paulo UNIFESP, Postgrad Program Biotechnol, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Programs Biotechnol & Struct & Funct Bio, Dept Ciencias Biol, Thyroid Mol Sci Lab,UNIFESP, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilHosp Sirio Libanes, Mol Oncol Ctr, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Postgrad Program Biotechnol, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Postgrad Programs Biotechnol & Struct & Funct Bio, Dept Ciencias Biol, Thyroid Mol Sci Lab,UNIFESP, Pedro Toledo 669, BR-04039903 Sao Paulo, SP, BrazilFAPESP [2009/53840-0]FAPESP[2010/12005-9, 2014/24549-4]Web of Scienc

Polymorphism on codon 98 of the galectin-3 gene are not associated to benign and nalignant thyroid tumors

Galectin-3 is a multifunctional protein highly expressed in thyroid cancer. The galectin-3 gene (LGALS3) has several annotated candidates SNPs, however the relationship between galectin-3 SNPs and specific phenotypic variations relevant to health has not been evaluated. In this study, we investigated SNPs in the galectin-3 gene and a putative association with thyroid tumorigenesis. The presence of LGALS3 SNPs in thyroid carcinoma cell lines (NPA, TPC-1, WRO, ARO), thyroid tissues of 55 patients with multinodular goiter or papillary carcinoma diagnosis and lymphocytes of peripherical blood of 45 healthy individuals was evaluated by sequencing and SSCP. The analysis of LGALS3 coding sequence showed that the T98P site presents a great genotypic variation, since we observed both homozygous (AA or CC) and heterozygous (AC) patterns. In thyroid carcinoma cell lines, the genotype of NPA in the LGALS3 T98P site is CC, while TPC-1, WRO and ARO are AC. The genotypic frequency of T98P SNP observed in multinodular goiter (AC= 67%; AA= 23%; CC= 10%) and papillary carcinoma (AC= 68%; AA= 20%; CC= 12%) were similar to the frequency observed in the control population (AC= 60%, AA= 24%, CC= 16%). In conclusion, no association between LGALS3 T98P genotype and the phenotype of the benign or malignant thyroid tumor was observed.Galectina-3 é uma proteína multifuncional altamente expressa em câncer de tiróide. O gene de galectina-3 (LGALS3) apresenta vários candidatos a SNPs anotados, no entanto a relação entre estes SNPs e variações fenotípicas específicas relevantes à saúde não foi avaliada. Neste estudo, investigamos SNPs do LGALS3 e uma possível associação destes com a tumorigênese tiroidiana. A presença de SNPs do LGALS3 em linhagens de carcinoma de tiróide (WRO, NPA, TPC-1, ARO), tecidos tiroidianos de 55 pacientes com diagnóstico de bócio multinodular ou carcinoma papilífero e linfócitos do sangue periférico de 45 indivíduos saudáveis foi avaliada por seqüenciamento e SSCP. A análise da seqüência codificadora do LGALS3 mostrou que o sítio T98P apresenta uma grande variação genotípica, visto que observamos os padrões homozigoto (AA ou CC) e heterozigoto (AC). Em linhagens de carcinoma de tiróide, o genótipo da NPA no sítio T98P do LGALS3 é CC, enquanto TPC-1, WRO e ARO são AC. As freqüências genotípicas do T98P do LGALS3 observadas em bócio multinodular (AC= 67%, AA= 23%, CC= 10%) e carcinoma papilífero (AC= 68%, AA= 20%, CC= 12%) foram semelhante à freqüência observada na população controle (AC= 60%, AA= 24%, CC= 16%). Em conclusão, não observamos associação entre o genótipo T98P do LGALS3 e o fenótipo de tumor benigno ou maligno de tiróide.10751081Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Anatomic Landmarks for Localization of the Spinal Accessory Nerve

This anatomical study examines the anatomic topography and landmarks for localization of the spinal accessory nerve (SAN) during surgical dissections in 40 fresh human cadavers (2 females and 38 males; ages from 22 to 89 years with a mean of 60 years). In the submandibular region, the SAN was found anteriorly to the transverse process of the atlas in 77.5% of the dissections. When the SAN crossed the posterior belly of the digastric muscle, the mean distance from the point of crossing to the tendon of the muscle was 1.75 +/- 0.54 cm. Distally, the SAN crossed between the two heads of the SCM muscle in 45% of the dissections and deep to the muscle in 55%. The SAN exited the posterior border of the sternocleidomastoid muscle in a point superior to the nerve point with a mean distance between these two anatomic parameters of 0.97 +/- 0.46 cm. The mean overall extracranial length of the SAN was 12.02 +/- 2.32 cm, whereas the mean length of the SAN in the posterior triangle was 5.27 +/- 1.52 cm. There were 2-10 lymph nodes in the SAN chain. In conclusion, the nerve point is one of the most reliable anatomic landmarks for localization of the SAN in surgical neck dissections. Although other anatomic parameters including the transverse process of the atlas and the digastric muscle can also be used to localize the SAN, the surgeon should be aware of the possibility of anatomic variations of those parameters. Similar to previous investigations, our results suggest that the number of lymph nodes of the SAN chain greatly varies. Clin. Anat. 22:471-475, 2009. (c) 2009 Wiley-Liss, Inc

Association of low sodium-iodide symporter messenger ribonucleic acid expression in malignant thyroid nodules with increased intracellular protein staining

Context: The expression of sodium iodide symporter (NIS) is required for iodide uptake in thyroid cells. Benign and malignant thyroid tumors have low iodide uptake. However, previous studies by RT-PCR or immunohistochemistry have shown divergent results of NIS expression in these nodules. Objective: The objective of the study was to investigate NIS mRNA transcript levels, compare with NIS and TSH receptor proteins expression, and localize the NIS protein in thyroid nodules samples and their surrounding nonnodular tissues (controls). Design: NIS mRNA levels, quantified by real-time RT-PCR, and NIS and TSH receptor proteins, evaluated by immunohistochemistry, were examined in surgical specimens of 12 benign and 13 malignant nodules and control samples. Results: When compared with controls, 83.3% of the benign and 100% of the malignant nodules had significantly lower NIS gene expression. Conversely, 66.7% of the benign and 100% of malignant nodules had stronger intracellular NIS immunostaining than controls. Low gene expression associated with strong intracellular immunostaining was most frequently detected in malignant (100%) than benign nodules (50%; P = 0.005). NIS protein was located at the basolateral membrane in 24% of the control samples, 8.3% of the benign, and 15.4% of the malignant nodules. The percentage of benign nodules with strong TSH receptor positivity (41.6%) was higher than malignant (7.7%). Conclusion: We confirmed that reduced NIS mRNA expression in thyroid malignant nodules is associated with strong intracellular protein staining and may be related to the inability of the NIS protein to migrate to the cellular basolateral membrane. These results may explain the low iodide uptake of malignant nodules.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Sao Paulo, Brazil[03/08900-9]Instituto da Tiroide, Sao Paulo, Brazi