Differentiated thyroid carcinoma: what the nonspecialists needs to know.

Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Differentiated thyroid carcinoma: what the nonspecialists needs to know

ABSTRACT Differentiated thyroid carcinoma (DTC) accounts for most cases of thyroid cancer, and the heterogeneity of DTC requires that management decisions be taken by a multidisciplinary team involving endocrinologists, head and neck surgeons, nuclear medicine physicians, pathologists, radiologists, radiation oncologists, and medical oncologists. It is important for nonspecialists to recognize and refer patients with DTC who will benefit from a specialized approach. Recent advances in knowledge and changes in management of DTC call for the need to raise awareness on the part of these nonspecialist physicians, including general endocrinologists and medical oncologists at large. We provide an overview of diagnostic and therapeutic principles in DTC, especially those that bear direct implication on day-to-day management of these patients by generalists. Patients with DTC may be broadly categorized as having localized, locally persistent/recurrent, or metastatic disease. Current recommendations for DTC include a three-tiered system that classifies patients with localized disease into low, intermediate, or high risk of persistent or recurrent disease. Risk stratification should be performed at baseline and repeated on an ongoing basis, depending on clinical evolution. One of the overarching goals in the management of DTC is the need to personalize treatment by tailoring its modality and intensity according to ongoing prognostic stratification, evolving knowledge about the disease, and patient characteristics and preference. In metastatic disease that is refractory to radioactive iodine, thyroid tumors are being reclassified into molecular subtypes that better reflect their biological properties and for which molecular alterations can be targeted with specific agents.

Physicians' preferences for radioiodine treatment of differentiated thyroid cancer in Brazil: an observational study

ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians' preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.

BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Treatment of Graves' disease in Brazil: results of a survey among endocrinologists

ABSTRACT Objective: The objective of the study was to determine how physicians in Brazil manage Graves' disease in different scenarios including extrathyroidal manifestations. Materials and methods: This study was conducted via a digital survey. The respondents (n = 573) answered multiple-choice questions based on a clinical case and variations of the case regarding laboratory and imaging evaluation, treatment choice, and follow-up. Results: The preferred initial treatment chosen by 95% of the respondents was ATD with a preferred treatment duration of 18-24 months. For 5% of the respondents, RAI was the initial treatment of choice. None of the respondents chose thyroidectomy. When presented with a patient with a desire for pregnancy in the near future, most respondents (69%) opted for ATD as the initial treatment. For a patient with signs of mild to moderate Graves' orbitopathy, ATD remained the initial therapy for 93.9% of the respondents. For patients initially treated with ATD with disease recurrence after ATD interruption, most respondents (60%) chose definitive treatment with RAI. A similar survey published in 2011 by Burch and cols. had results comparable to those of the present survey but with a higher proportion of respondents choosing RAI (45% in the 2011 survey versus 5% in the present survey). Conclusion: Brazilian endocrinologists choose ATD as the initial management of Graves' disease, and most choose RAI as a definitive treatment for a patient with relapse after ATD therapy.

Análise descritiva da mini avaliação nutricional em idosos da universidade aberta à terceira idade ­ UATI / Descriptive analysis of the mini nutritional assessment in the elderly at the open university for the third age ­ UATI

Introdução: o envelhecimento populacional é um fenômeno universal devido ao processo de transição demográfica característico de diversos países. Nesse processo, observam-se alterações fisiológicas e nutricionais nos indivíduos, acompanhadas do declínio das atividades funcionais cotidianas. A Mini Avaliação Nutricional foi desenvolvida para detectar a desnutrição ou o risco nutricional. Trata ­ se de uma ferramenta simples, de fácil aplicação, efetiva e validada, para utilização em pacientes idosos. Objetivo: avaliar o estado nutricional através da aplicação da Mini Avaliação Nutricional (MAN) e fatores associados em idosos frequentadores da Universidade Aberta à Terceira Idade (UATI), situada em Salvador, Bahia. Metodologia: trata-se de um estudo observacional, analítico e de corte transversal, em que foram avaliados 52 idosos a partir de 60 anos, de ambos os sexos, admitidos entre os meses de fevereiro e junho de 2021. Na avaliação do estado nutricional, utilizou ­ se a MAN e, para a análise estatística, foi aplicado o programa Statistical Package for Social Science 20.0. A amostra foi categorizada em três grupos: adequado, risco de desnutrição e desnutrição. Utilizou-se o teste de qui quadrado, considerando p<0,05. Conclusão: os Resultados encontrados neste estudo mostram que há prevalência e um elevado risco de desnutrição nos pacientes idosos da UATI. Os grupos estudados se caracterizam por maior frequência do sexo feminino, faixa etária entre 60 e 69 anos, sem ocupação e com hipossuficiência financeira. A aplicação desse método de avaliação nutricional em idosos é de baixo custo e de fácil reprodutividade e tem demonstrado eficácia no rastreio da desnutrição de forma precoce, proporcionando intervenções nutricionais mais rápidas e efetivas, especialmente no contexto da saúde pública.

Introduction: population aging is a universal phenomenon due to the demographic transition process characteristic of several countries. In this process, physiological and nutritional changes are observed in individuals, accompanied by a decline in daily functional activities. The mini nutritional assessment was developed to detect malnutrition or nutritional risk. It is a simple, easy-to-apply, effective and validated tool for use in elderly patients. Objective: to evaluate the nutritional status through the application of the mini nutritional assessment (man) and associated factors in elderly people attending the universidade aberta à terceira idade (uati) [open university for the third age ­ elderly], located in salvador, bahia. Methods: this is an observational, analytical and cross-sectional study, in which 52 elderly people aged 60 years and over, of both sexes, admitted between february and june 2021, were evaluated. In the assessment of nutritional status, man was used and, for statistical analysis, the statistical package for social science 20.0 program was applied. The sample was categorized into three groups: adequate, risk of undernutrition and malnutrition. The chi-square test was used, considering p<0.05. Conclusion: the Results found in this study show that there is a prevalence and a high risk of malnutrition in elderly patients at the uati. The groups studied are characterized by a higher frequency of females, aged between 60 and 69 years, without occupation and with financial deficiency. The application of this method of nutritional assessment in the elderly is low-cost and easily reproducible and has been shown to be effective in screening for malnutrition at an early stage, providing faster and more effective nutritional interventions, especially in the context of public health.

Feasibility of a snowball sampling survey to study active surveillance for thyroid microcarcinoma treatment among endocrinologists and surgeons of Brazil

Abstract Objectives: This study aims to investigate if a sampling method using virtual networks is feasible to survey AS adoption among this "hard-to-reach" population of Brazilian doctors. Methods: An online piloted 11-point structured survey questionnaire (designed using Googleforms®) probed the actual treatment patterns for adult patients with PTMCs, including treatment decision-making nonoperative options, was undertaken between 10 November and 30 November 2020. Participants were reached by the mobile phone Application (APP) and a snowball sampling strategy was used to recruit a total of 4783 members (maximum number of potential reach), which is the total of doctors of the all 21 social media WhatsApp® groups. Results: From a total of 4783 members (maximum number of potential reach), there were 657 (13.7%) doctors (actual reach) who clicked the web link of the questionnaire, out of whom 512 (10.7%) fully completed the online survey. Among the survey respondents, 361 were endocrinologists (70.5%) and 151 were surgeons (29.5%). Overall, for low-risk PTMCs in an elderly patient, 118 responders (23%) recommend AS, while 390 (76%) recommend immediate surgery as the management, including lobectomy (18.5%) and Total Thyroidectomy (58.2%). The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or raised the size during the follow-up. Conclusion: Using snowball sampling strategy as an innovative route to conduct surveys was feasible and applicable but the rate of response was still very low. Our data also suggests the need to investigate if AS is embraced by Brazilian doctors.

Approach to adult patients with primary hypothyroidism in some special situations: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

Clinical decision support analysis of a microRNA-based thyroid molecular classifier: A real-world, prospective and multicentre validation study.

BACKGROUND: The diagnosis of cancer in Bethesda III/IV thyroid nodules is challenging as fine-needle aspiration (FNA) has limitations, and these cases usually require diagnostic surgery. As approximately 77% of these nodules are not malignant, a diagnostic test accurately identifying benign thyroid nodules can reduce "potentially unnecessary" surgery rates. We have previously reported the development and validation of a microRNA-based thyroid classifier (mir-THYpe) with high sensitivity and specificity, which could be performed directly from FNA smear slides. We sought to evaluate the performance of this test in real-world clinical routine to support clinical decisions and to reduce surgery rates. METHODS: We designed a real-world, prospective, multicentre study. Molecular tests were performed with FNA samples prepared at 128 cytopathology laboratories. Patients were followed-up from March 2018 until surgery or until March 2020 (patients with no indication for surgery). The final diagnosis of thyroid tissue samples was retrieved from postsurgical anatomopathological reports. FINDINGS: A total of 435 patients (440 nodules) classified as Bethesda III/IV were followed-up. The rate of avoided surgeries was 52·5% for all surgeries and 74·6% for "potentially unnecessary" surgeries. The test achieved 89·3% sensitivity, 81·65% specificity, 66·2% positive predictive value, and 95% negative predictive value. The test supported 92·3% of clinical decisions. INTERPRETATION: The reported data demonstrate that the use of the microRNA-based classifier in the real-world can reduce the rate of thyroid surgeries with robust performance and support clinical decision-making. FUNDING: The São Paulo Research-Foundation (FAPESP) and Onkos.

Feasibility of a snowball sampling survey to study active surveillance for thyroid microcarcinoma treatment among endocrinologists and surgeons of Brazil.

OBJECTIVES: This study aims to investigate if a sampling method using virtual networks is feasible to survey AS adoption among this "hard-to-reach" population of Brazilian doctors. METHODS: An online piloted 11-point structured survey questionnaire (designed using Googleforms®) probed the actual treatment patterns for adult patients with PTMCs, including treatment decision-making nonoperative options, was undertaken between 10 November and 30 November 2020. Participants were reached by the mobile phone Application (APP) and a snowball sampling strategy was used to recruit a total of 4783 members (maximum number of potential reach), which is the total of doctors of the all 21 social media WhatsApp® groups. RESULTS: From a total of 4783 members (maximum number of potential reach), there were 657 (13.7%) doctors (actual reach) who clicked the web link of the questionnaire, out of whom 512 (10.7%) fully completed the online survey. Among the survey respondents, 361 were endocrinologists (70.5%) and 151 were surgeons (29.5%). Overall, for low-risk PTMCs in an elderly patient, 118 responders (23%) recommend AS, while 390 (76%) recommend immediate surgery as the management, including lobectomy (18.5%) and Total Thyroidectomy (58.2%). The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or raised the size during the follow-up. CONCLUSION: Using snowball sampling strategy as an innovative route to conduct surveys was feasible and applicable but the rate of response was still very low. Our data also suggests the need to investigate if AS is embraced by Brazilian doctors.

Composição corporal por meio da absortometria radiológica de dupla energia em idosos institucionalizados do Hospital Santo Antônio / Body composition through dual energy radiological absorptiometry of institutionalized elderly at Hospital Santo Antônio

Introdução: o processo de envelhecimento tem sido constante objeto de estudos epidemiológicos, em função do recrudescimento do número de idosos na população, resultando numa incessante busca de instituições de longa permanência. O uso de métodos de avaliação nutricional e de composição corporal em idosos dessas instituições pode ser considerado um diferencial na assistência multimodal. Objetivo: avaliar a composição corporal de idosos institucionalizados por meio da Absortometria Radiológica de Dupla Energia, atendidos do Hospital Santo Antônio, na cidade de Salvador, Bahia. Metodologia: estudo descritivo, analítico, corte transversal, com 13 idosos de ambos os sexos da referida instituição. Aplicou-se questionário sociodemográfico e de dados clínicos e os idosos foram submetidos a DXA, obedecendo a protocolos padrão para realização do exame. Resultados: predominância do sexo feminino (61%) e idade média de 79,5 (DP=7,0). As mulheres se destacaram por excesso de gordura corporal (61,5%) e, no que tange à reserva de massa muscular, a distribuição percentual e absoluta foi dividida de forma igual para ambos os sexos (50%). Conclusões: foi possível observar que grande parte dos idosos avaliados, e em especial mulheres, apresentou excesso de tecido corporal gorduroso, considerando todas as variáveis relacionadas à massa gordurosa corporal reveladas pela DXA. Estudos dentro dessa temática, no último ciclo de vida mais vulnerável são de suma importância, uma vez que o número populacional de idosos tem assumido nos últimos anos um crescimento exponencial.

Introduction: the aging process has been a constant object of epidemiological studies, due to the increase in the number of elderly people in the population, resulting in an incessant search for long-term care facilities. The use of methods for nutritional assessment of body composition in the elderly in these institutions can be considered a differential in multimodal care. Objective: assessing the body composition of elderly institutionalized people using dual energy X-ray absorptiometry at Santo Antônio Hospital, in the city of Salvador, Bahia. Methodology: descriptive, analytical, cross-sectional study with 13 elderly people male and female from that institution. A sociodemographic and clinical data questionnaire was applied and the elderly were submitted to DXA, following standard protocols for the examination. Results: prevalence of females (61%) and mean age of 79.5 (SD=7.0). Women stood out due to excess body fat (61.5%) and, with regard to muscle mass reserve, the percentage and absolute distribution was equally divided for men and women (50%). Conclusion: it was possible to observe that most of the elderly evaluated, and especially women, had excess body fat tissue, considering all variables related to body fat mass revealed by DXA. Studies into this theme are crucial in the last most vulnerable life cycle, since the number of elderly population has assumed an exponential growth in recent years.

Carcinoma papilífero de tireoide pediátrico associado à fusão gênica RET-PTC6: relato de caso / Pediatric papillary thyroid carcinoma associated with RET-PTC6 gene fusion: a case report

Introdução: o carcinoma papilífero de tireoide é a neoplasia maligna que mais acomete o sistema endócrino, correspondendo a cerca de 90% dos casos. Diante de sua frequência, nas últimas décadas, foi registrado um aumento do número de casos na população pediátrica e, devido a isso, o número de crianças e adolescentes submetidos à tireoidectomia se tornou cada vez maior. Enquanto as alterações gênicas mais encontradas em adultos com carcinoma papilífero concentram-se em mutações pontuais, na população pediátrica as fusões gênicas são mais frequentes, com destaque para os rearranjos RET/PTC. Objetivo: relatar aspectos clínico-patológicos do carcinoma papilífero de tireoide, associado à fusão do gene RET, em criança submetida à tireoidectomia e radioiodoterapia adjuvante. Em seguida, discute-se a importância do diagnóstico molecular na escolha de terapias relevantes no tratamento do CPT. Caso Clínico: trata-se de uma paciente do sexo feminino, 11 anos de idade, submetida a tireoidectomia total e esvaziamento cervical após diagnóstico do referido carcinoma. O estudo anatomopatológico revelou um carcinoma metastático em linfonodos regionais. Utilizou-se uma amostra de tecido em bloco de parafina para a realização de um sequenciamento de nova geração, que apontou a existência da fusão gênica TRIM24-RET. Conclusão: os dados deste relato de caso evidenciam que a mutação RET/PTC6 está muito associada à população pediátrica e que testes moleculares, como o NGS, são de extremo valor na identificação dessas alterações gênicas e, consequentemente, na terapia a ser adotada para cada paciente.

Introduction: thyroid papillary carcinoma is the malignant neoplasm that most affects the endocrine system, corresponding to about 90% of cases. Given its frequency, in recent decades, there has been an increase in the number of cases in the pediatric population and, as a result, the number of children and adolescents undergoing thyroidectomy has become increasingly larger. While the most common gene alterations found in adults with papillary carcinoma are concentrated in point mutations, in the pediatric population gene fusions are more frequent, with emphasis on the RET/PTC rearrangements. Objective: to report clinical and pathological aspects of papillary thyroid carcinoma associated with RET gene fusion in a child undergoing thyroidectomy and adjuvant radioiodine therapy. Then, the importance of molecular diagnosis in choosing relevant therapies in the treatment of PTC is discussed. Clinical Case: this is an 11-year-old female patient who underwent total thyroidectomy and neck dissection after diagnosis of the aforementioned carcinoma. The anatomopathological study revealed a metastatic carcinoma in regional lymph nodes. A tissue sample in paraffin block was used to perform a new generation sequencing, which showed the existence of the TRIM24-RET gene fusion. Conclusion: the data in this case report show that the RET/PTC6 mutation is closely associated with the pediatric population and that molecular tests, such as the NGS, are extremely valuable in identifying these genetic alterations and, consequently, in the therapy to be adopted for each patient.

Mutação do promotor TERT no carcinoma anaplásico da tireoide: um relato de caso / TERT promoter mutation in anaplastic thyroid carcinoma: a case report

Introdução: o gene TERT codifica a subunidade catalítica da telomerase responsável pelo alongamento dos telômeros no final dos cromossomos. Mutações na região promotora do gene TERT resultam em superexpressão da subunidade catalítica e promovem aumento da atividade da telomerase, fatos que levam ao aumento da incidência do câncer. No carcinoma anaplásico da tireoide, essas mutações são preditores de pior prognóstico e estão associadas a comportamento clínico agressivo, incluindo alta frequência de recidivas, metástases a distância e morte específica pela doença. Objetivo: relatar o caso de uma paciente idosa portadora de carcinoma anaplásico da tireoide, cujo teste de sequenciamento genético revelou a mutação do promotor TERT C228T. Caso clínico: mulher idosa, 66 anos, diagnosticada inicialmente com nódulo tireoidiano, o qual cresceu rapidamente em um curto período de tempo. Diante da suspeita de neoplasia maligna, a paciente foi submetida a tireoidectomia total, com realização de esvaziamento cervical. Os estudos anatomopatológico e imuno-histoquímico do tumor confirmaram o carcinoma. Estudos moleculares realizados a partir da tecnologia do sequenciamento de nova geração negaram a presença de fusões gênicas, porém detectaram a mutação TERT C228T. Discussão: a identificação da mutação no promotor TERT C288T reforça a hipótese de que mutações TERT são frequentes em tumores tireoidianos mais agressivos, como é o caso do carcinoma anaplásico da tireoide. Conclusão: os dados apresentados neste estudo reforçam a premissa de que mutações no promotor TERT são preditores de pior prognóstico e de comportamento clínico mais agressivo.

Introduction: the TERT gene encodes the catalytic telomerase subunit responsible for elongating telomeres at the end of chromosomes. Mutations in the promoter region of the TERT gene result in overexpression of the catalytic subunit and promote increased telomerase activity, facts that lead to an increased incidence of cancer. In anaplastic thyroid carcinoma, these mutations are predictors of worse prognosis and are associated with aggressive clinical behavior, including a high frequency of relapses, distant metastases, and diseasespecific death. Objective: to report the case of an elderly patient with anaplastic thyroid carcinoma, whose gene sequencing test revealed a TERT C228T promoter mutation. Case report: Elderly woman, 66 years old, initially diagnosed with a thyroid nodule, which grew rapidly in a short period of time. Given the suspicion of malignant neoplasm, the patient underwent total thyroidectomy, with neck dissection. The anatomopathological and immunohistochemical studies of the tumor confirmed the carcinoma. Molecular studies performed using next-generation sequencing technology denied the presence of gene fusions, but detected the TERT C228T mutation. Discussion: identification of the mutation in the TERT C288T promoter reinforces the hypothesis that TERT mutations are frequent in more aggressive thyroid tumors, such as anaplastic thyroid carcinoma. Conclusion: data presented in this study reinforce the premise that mutations in the TERT promoter are predictors of worse prognosis and more aggressive clinical behavior.

Congenital hypothyroidism and thyroid cancer.

Differentiated thyroid carcinoma (DTC) combined with congenital hypothyroidism (CH) is a rare situation, and there is no well-established causal relationship. CH is a common congenital endocrine, while DTC occurring in childhood represents 0.4-3% of all malignancies at this stage of life. The association of CH with DTC could be related to dyshormonogenetic goiter (DHG) or developmental abnormalities. This review will explore the clinical features and the molecular mechanisms potentially associated with the appearance of DTC in CH: sporadic somatic driver mutations, chronic increase of thyroid-stimulating hormone (TSH) levels, higher concentrations of hydrogen peroxide (H2O2), cell division cycle associated 8 (Borelain/CDC8) gene mutations, and in others genes associated with CH - either alone or associated with the mechanisms involved in dyshormonogenesis. There are some pitfalls in the diagnosis of thyroid cancer in patients with CH with nodular goiter, as the proper cytological diagnosis of nodules of patients with dyshormonogenesis might be demanding due to the specific architectural and cytological appearance, which may lead to an erroneous interpretation of malignancy. The purpose of this article is to suggest an analytical framework that embraces the fundamental relationships between the various aspects of CH and CDT. In face of this scenario, the entire genetic and epigenetic context, the complex functioning, and cross talk of cell signaling may determine cellular mechanisms promoting both the maintenance of the differentiated state of the thyroid follicular cell and the disruption of its homeostasis leading to cancer. Whereas, the exact mechanisms for thyroid cancer development in CH remain to be elucidated.

Long-term follow-up and safety of vandetanib for advanced medullary thyroid cancer.

INTRODUCTION: Vandetanib is indicated for adults with advanced medullary thyroid cancer (MTC). OBJECTIVES: To describe the efficacy and toxicity profile of vandetanib treatment with a maximal follow-up of 11 years at Institut Gustave Roussy/France. METHODS: A review of the clinical files of the 76 MTC patients treated with vandetanib. Efficacy was estimated by markers and imaging. RESULTS: A total of 76 patients received vandetanib. Nine were excluded from efficacy analysis because lack of morphological data. The overall (N = 76) median treatment duration was 17.6 (range: 0.7-130.6) months and the median progression-free survival (PFS) was 22.7 (95% CI, 13.9-37.3) months. In total, 21/76 (27.6%) patients were classified as long-term users because have received vandetanib for more than 48 months, with a median treatment duration of 68.1 (range: 49.1-130.6) months. For long-term vandetanib users, the objective response rate was 85.7%, the median time to best response was 27.8 (11.6.1-110) months and the median duration of response was 70.4 (38.3-127.5) (95% CI 49.5-102.8) months with a median PFS of 73.2 (95% CI, 53.1-105.6) months. Duration of response had a significant negative correlation with patient age at diagnosis (p = 0.03) and was significantly higher in patients that did not have confirmed tumor progression before treatment onset (p = 0.007). After 48 months of vandetanib use, renal failure took place in two patients and heart failure, cholecystitis, acute pancreatitis, posterior encephalopathy, and skin cancer first occurred in one patient, each. CONCLUSIONS: Our findings suggest that a substantial number of patients receiving first-/second-line vandetanib may sustain long clinical benefit and that a younger age at diagnosis and the absence of progression before treatment could be considered as predictors of durable response.

Prevalência de sobrepeso e obesidade em idosas frequentadoras da Universidade Aberta da Terceira Idade ­ UATI / Prevalence of overweight and obesity in elderly people attending the Open University of the Elderly ­ UATI

Introdução: este artigo trata-se da prevalência de sobrepeso e obesidade em idosas frequentadoras da Universidade Aberta da Terceira Idade. Objetivo: avaliar as prevalências de sobrepeso e de obesidade associadas a fatores socioeconômicos e presença de comorbidades, em uma amostra de idosas não institucionalizadas de Salvador-BA, Brasil. Metodologia: um estudo transversal com uma amostra de 72 idosas com mais de 60 anos frequentadoras da Universidade Aberta da Terceira Idade (UATI) vinculada a Universidade Estadual da Bahia (UNEB). Foram aplicados questionários as participantes sobre aspectos pessoais, sócio-demográficos e presença de comorbidades. Resultados: os dados antropométricos avaliados foram o Índice de Massa Corporal (IMC) e da Circunferência da Cintura (CC). Associações entre as variáveis categóricas foram testadas utilizando o teste qui-quadrado com um nível de significância 5%. Observou-se que prevalência de sobrepeso e obesidade de acordo com o IMC foi de 34,48% e 24,14%, respectivamente e 86,54% dos idosos apresentaram um substancial aumento da circunferência abdominal. Verificou-se que 13,46% dos indivíduos eram diabéticos, 63,46% hipertensos. Conclusão: neste estudo não houve associação com significância estatística entre excesso de peso e renda ou presença de comorbidades (Diabete Melito e Hipertensão).

Introduction: the aim of this study was to evaluate the prevalence of overweight and obesity associated with socioeconomic factors and the presence of comorbidities, in a sample of non-institutionalized elderly women from Salvador-BA, Brazil. Metodology: crosssectional study was carried out with a sample of 72 elderly women over 60 years of age attending the Open University of the Third Age (UATI) linked to the State University of Bahia (UNEB). Questionnaires were applied to participants on personal, socio-demographic and presence of comorbidities. Results: the anthropometric data evaluated were the body mass index (BMI) and waist circumference (WC). Associations between categorical variables were tested using the chi-square test with a 5% significance level. It was observed that the prevalence of overweight and obesity according to the BMI was high (34.48% and 24.14%, respectively) and 86.54% of the elderly showed a substantial increase in waist circumference. It was found that 13.46% of the individuals were diabetic, 63.46% were hypertensive. Conclusion: It was observed that BMI was not significantly associated (p <0.05) with income or the presence of comorbidities (Diabetes Mellitus and Hypertension).

Avaliação de dinapenia e associação com função tireoidiana em idosos da Universidade Aberta à Terceira Idade ­ UATI / Evaluation of dynapenia and association with thyroid function in elderly at the Open University of the Elderly ­ UATI

Introdução: o presente artigo analisou e avaliou a prevalência de dinapenia em associação da idade dos Hormônio Estimulador da tireoide (TSH) e T3 em idosos da Universidade Aberta à Terceira Idade ­ UATI. A tireoide produz e secreta os hormônios triiodotironina (T3) e tiroxina (T4), responsáveis por controlar o metabolismo celular. O termo dinapenia tem sido utilizado para descrever a diminuição da força muscular relacionada à idade separando desta forma, a dinapenia da redução da massa muscular. Metodologia: trata-se de um estudo de corte transversal que investigou 63 mulheres com idade entre 60 e 95 anos, resultando numa idade média das participantes foi de 69,6 anos, não institucionalizadas, matriculados no projeto "Universidade Aberta à Terceira Idade (UATI)", da Universidade Estadual da Bahia (UNEB). A força de preensão palmar (FPP) foi avaliada em quilograma (kg), por meio do dinamômetro digital manual da marca INSTRUTHERM. Resultados: foram diagnosticados com dinapenia as pacientes que possuíram a FPP inferior a 20 kg. Descobriu-se que 23 idosas (36,51%) foram diagnosticadas com dinapenia. A correlação entre as variáveis TSH e dinapenia foi positiva e fraca Spearman=0.17 (p-valor= 0.22). Assim, a relação entre o FPP e a idade não parece ser linear possuindo uma correlação negativa e fraca: Spearman= -0.11 (p-valor= 0.39). Conclusão: o nível sérico de TSH e idade não tiveram associação significativa com a presença de dinapenia. Houve associação entre T3 sérico e dinapenia, porém não é possível identificar em qual quartil está essa associação.

Introduction: this article analyzed and evaluated the prevalence of dynapenia in association with the age of thyroid stimulating hormones (TSH) and T3 in the elderly at Universidade Aberta do Idoso ­ UATI. The thyroid produces and secretes the hormones triiodothyronine (T3) and thyroxine (T4) responsible for the control of cellular metabolism. The term dynapenia has been used to describe the decrease in muscle strength related to age, separating dynapenia from the reduction of muscle mass. Methodology: this is a cross-sectional study that investigated 63 women between 60 and 95 years old, resulting in an average age of participants of 69.6 years old, non-institutionalized, registered in the project the Open University Of The Elderly (UATI)", of Bahia State University (UNEB). The Hand Grip Strength (HGS) was measured in kilograms (kg), using the INSTRUTHERM manual digital dynamometer. Results: patients with FPP less than 20 kg were diagnosed with dynapenia. It was found that 23 elderly women (36.51%) were diagnosed with dynapenia. The correlation between TSH and dynapenia variables was positive and weak Spearman = 0.17 (p-value = 0.22). Thus, the relationship between (FPP) and age does not appear to be linear with a weak and negative correlation: Spearman = -0.11 (p-value = 0.39). Conclusion: the serum TSH level and age had no significant association with the presence of dynapenia. There was an association between(T3) and serum dinapenia, but it is not possible to identify in which quartile this association is found.

Carcinoma anaplásico de tireoide: relato de caso tratado com cirurgia e radioterapia adjuvante / Anaplastic thyroid cancer: a case report treated with surgery and adjuvant radiotherapy

Introdução: o Carcinoma Anaplásico de Tireoide (CAT) está entre as mais letais malignidades humanas, sendo a taxa de sobrevida estimada em 10-20% em 01 ano e menor que 5% em 10 anos. Diante da raridade do CAT e desfecho consideravelmente desfavorável da doença, este relato discute as modalidades terapêuticas utilizadas no tratamento do CAT e as características da doença possivelmente relacionadas a um melhor desfecho clínico. Objetivo: relatar o caso de um paciente idoso portador de CAT com resposta completa loco-regional após tratamento combinado com cirurgia e radioterapia (RT) adjuvante. Neste estudo, a literatura a respeito das características da patologia da neoplasia indiferenciada da tireoide e modalidades de tratamento no controle oncológico desta doença é revisada e discutida. Caso clínico: trata-se de um paciente masculino de 88 anos submetido a Tireoidectomia Total (TT) cujo estudo imuno-histoquímico evidenciou neoplasia maligna indiferenciada da tireoide. O paciente realizou tratamento adjuvante com RT na dose total de 66 Gy em leito operatório. Em tempo de seguimento de 18 meses, o paciente encontra-se vivo sem doença detectável em atividade. Conclusão: neste relato, descreveu-se um raro caso de uma evolução favorável de um paciente idoso portador de CAT com longa sobrevida livre de doença quando comparada ao prognóstico reservado dessa neoplasia. Este relato destaca a importância de uma terapia multimodal no manejo desta doença.

Backgroud: anaplastic thyroid cancer (ATC) ranks among the most lethal of all human malignancies, and the estimated survival rate ranges from 10 to 20% in 01 year and is less than 5% in 10 years. In view of the rarity of ATC and considerably unfavorable outcome of the disease, this report makes it possible to discuss the therapeutic modalities in the treatment of the ATC and the features of the disease possibly related to a better clinical outcome. Objective: the objective of the present study is to report the case of an elderly patient with ATC with locoregional complete response after combined treatment with surgery and adjuvant radiotherapy (RT.) In this study, the literature regarding the pathological features of the undifferentiated thyroid cancer and treatment modalities on oncologic outcome is reviewed and discussed. Case presentation: this is a case of a 88 year old male patient, who underwent total thyroidectomy (TT) for thyroid cancer treatment whose cytological analysis was compatible with anaplastic thyroid cancer. The immunohistochemical study showed undifferentiated malignancy of the thyroid. The patient underwent adjuvant treatment with RT at the total dose of 66 Gy in operative bed. In a follow-up period of 18 months, the patient is alive with no detectable disease in activity. Conclusions: in this report, is described a rare case of a favorable evolution of an elderly patient with ATC relatively long disease-free survival compared to the reserved prognosis of this neoplasm. This case underlines the importance of a multimodal therapy in the management of this disease.

Preoperative detection of TERT promoter and BRAFV600E mutations in papillary thyroid carcinoma in high-risk thyroid nodules

ABSTRACT Objectives: This observational study analyzed telomerase reverse transcriptase (pTERT) mutations in 45 fine-needle aspiration (FNA) specimens obtained from thyroid nodules followed by postoperatively confirmation of papillary thyroid cancer (PTC) diagnosis, examining their relationship with clinicopathologic aspects and the BRAFV600E mutation. Subjects and methods: Clinical information was collected from patients who presented to Ribeirao Preto University Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between January 2010 to October 2012. Tests included a DNA-based somatic detection of BRAFV600E and pTERT mutations. Results: We found coexistence of pTERTC228T and BRAFV600E mutations in 8.9% (4/45) of thyroid nodules. All nodules positive for pTERT mutations were BRAFV600E positives. There was a significant association between pTERTC228T/BRAFV600E with older age and advanced stage compared with the group negative for either mutation. Conclusions: This series provides evidence that FNA is a reliable method for preoperative diagnosis of high-risk thyroid nodules. pTERTC228T/BRAFV600E mutations could be a marker of poor prognosis. Its use as a personalized molecular medicine tool to individualize treatment decisions and follow-up design needs to be further studied.