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.

Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil

Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. Materials and methods: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. Results: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. Conclusion: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Incidence of thyroid diseases: Results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: To evaluate incidence of subclinical and overt hyperthyroidism and hypothyroidism. Subjects and methods: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study of 15,105 civil servants, examined at baseline and over a 4-year follow-up. This analysis included 9,705 participants with normal thyroid function at baseline, follow-up information about thyroid function and with no report of using drugs that may interfere in the thyroid function. Thyroid function was defined by TSH/FT4 levels or routine use of thyroid hormones/anti-thyroid medications. Annual and cumulative (over 4-year) incidence rates were presented as percentages (95% Confidence Intervals). Results: The incidence of all overt and subclinical thyroid disease was 6.7% (1.73%/year): 0.19% for overt hyperthyroidism (0.048%/year), 0.54% for subclinical hyperthyroidism (0.14%/year), 1.98% for overt hypothyroidism (0.51%/year), and 3.99% for subclinical hypothyroidism (1.03%/year). The incidence of all thyroid diseases was higher in women, when compared to men, with a low women:men ratio (1.36). For Blacks the highest incidence was for overt hyperthyroidism, while for Whites, the highest incidence was for overt hypothyroidism. However, the highest incidence of overt hyperthyroidism was detected in Asian descendants. The presence of antithyroperoxidase antibodies at baseline was associated with higher incidence of overt thyroid diseases. Conclusion: These results showed a high incidence of hypothyroidism, which is compatible with a country with a more-than-adequate iodine intake. The low women:men ratio of the incidence of thyroid dysfunction highlights the importance of the diagnosis of thyroid diseases among men in Brazil.

Clinical practice guidelines for the management of hypothyroidism / Diretrizes clínicas práticas para o manejo do hipotiroidismo

INTRODUCTION: Hypothyroidism has long been known for its effects on different organ systems, leading to hypometabolism. However, subclinical hypothyroidism, its most prevalent form, has been recently related to cardiovascular risk and also to maternal-fetal complications in pregnant women. OBJECTIVES: In these clinical practice guidelines, several aspects of this field have been discussed with the clear objectives of helping physicians treat patients with hypothyroidism, and of sharing some of our Latin American-based clinical experience. MATERIALS AND METHODS: The Latin American Thyroid Society commissioned a Task Force on Hypothyroidism to develop evidence-based clinical guidelines on hypothyroidism. A systematic review of the available literature, focused on the primary databases of MedLine/PubMed and Lilacs/SciELO was performed. Filters to assess methodological quality were applied to select the best quality studies. The strength of recommendation on a scale from A-D was based on the Oxford Centre for Evidence--based Medicine, Levels of Evidence 2009, allowing an unbiased opinion devoid of subjective viewpoints. The areas of interest for the studies comprised diagnosis, screening, treatment and a special section for hypothyroidism in pregnancy. RESULTS: Several questions based on diagnosis, screening, treatment of hypothyroidism in adult population and specifically in pregnant women were posed. Twenty six recommendations were created based on the answers to these questions. Despite the fact that evidence in some areas of hypothyroidism, such as therapy, is lacking, out of 279 references, 73% were Grade A and B, 8% Grade C and 19% Grade D. CONCLUSIONS: These evidence-based clinical guidelines on hypothyroidism will provide unified criteria for management of hypothyroidism throughout Latin America. Although most of the studies referred to are from all over the world, the point of view of thyroidologists from Latin America is also given.

INTRODUÇÃO: O hipotiroidismo é amplamente reconhecido por seus efeitos sobre os diferentes sistemas orgânicos, levando ao hipometabolismo. No entanto, o hipotiroidismo subclínico, sua apresentação mais prevalente, tem sido recentemente relacionado ao risco cardiovascular e também com complicações materno-fetais em gestantes. OBJETIVOS: Nestas diretrizes clínicas, vários aspectos do hipotiroidismo foram discutidos com objetivos claros de ajudar os médicos a tratar pacientes com hipotiroidismo e de compartilhar algumas das nossas experiências clínicas na América Latina. MATERIAIS E MÉTODOS: A Sociedade Latino-Americana de Tireoide formou uma Força-Tarefa para desenvolver diretrizes baseadas em evidências clínicas sobre o hipotiroidismo. Foi realizada uma revisão sistemática da literatura existente, com foco em bancos de dados primários do MedLine/PubMed e Lilacs/SciELO. Foram feitas análises para avaliar a qualidade metodológica no sentido de selecionar os melhores estudos. A força de recomendação em uma escala de A-D foi baseada no Centro de Oxford para a Medicina Baseada em Evidência - Níveis de Evidência 2009 - , permitindo uma opinião imparcial, desprovida de pontos de vista subjetivos. As áreas de interesse compreenderam estudos de diagnóstico, triagem, tratamento e uma seção especial de hipotiroidismo na gravidez. RESULTADOS: Foram feitos vários questionamentos relacionados ao diagnóstico, triagem e tratamento do hipotiroidismo na população adulta e, especificamente, em mulheres grávidas. Foram elaboradas vinte e seis recomendações baseadas nas respostas a essas perguntas. Apesar da falta de evidências em algumas áreas como o tratamento do hipotiroidismo, de 279 referências, 73% eram de Grau A e B, 8% de Grau C e 19% de Grau D. CONCLUSÕES: Essas diretrizes baseadas em evidências clínicas sobre o hipotiroidismo poderão fornecer um critério consensual de como tratar o hipotiroidismo na América Latina. Apesar de a maior parte dos estudos referidos ser da experiência internacional em hipotiroidismo, o ponto de vista dos tiroidologistas da América Latina foi contemplado.

Patogênese das doenças tiroidianas autoimunes / Pathogenesis of autoimmune thyroid diseases

A doença tiroidiana autoimune (DAIT), que afeta de 2 por cento a 5 por cento da população ocidental, é o transtorno autoimune órgão-específico mais comum. Sua apresentação clínica varia do hipertiroidismo da doença de Graves (DG) ao hipotiroidismo associado à tiroidite de Hashimoto (TH). A exata etiologia da DAIT permanece desconhecida, mas a interação entre suscetibilidade genética e fatores ambientais desencadeadores parece ser de fundamental importância no seu desenvolvimento. Postula-se que fatores genéticos responderiam por 79 por cento da suscetibilidade à DAIT e os ambientais por 21 por cento. Genes imunomoduladores, como o complexo maior de histocompatibilidade (MHC), antígeno-4 associado ao linfócito T citotóxico (CTLA-4), a molécula CD40 e a proteína tirosina fosfatase-22 (PTPN22) e os genes específicos da glândula tiróide, como receptor do TSH (TSHR) e tiroglobulina (TG) têm sido identificados. A natureza exata do envolvimento do meio ambiente no desenvolvimento da DAIT não é bem conhecida, mas vários fatores ambientais têm sido envolvidos, como o conteúdo de iodo na dieta, estresse, drogas e infecções. Entretanto, não há evidência clara de causalidade e os mecanismos pelos quais fatores ambientais desencadeariam a autoimunidade tiroidiana, em indivíduos geneticamente predispostos, ainda permanecem não completamente entendidos. O conhecimento dos mecanismos precisos de interação entre fatores ambientais e genes na indução da autoimunidade tiroidiana poderia resultar desenvolvimento de novas estratégias de prevenção e tratamento.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder affecting 2 percent to 5 percent of the population in Western countries. Clinical presentation varies from hyperthyroidism in Graves' Disease to hypothyroidism in Hashimoto's thyroiditis. While the exact etiology of thyroid autoimmunity is not known, interaction between genetic susceptibility and environmental factors appears to be of fundamental importance to initiate the process of thyroid autoimmunity. It has been postulated that 79 percent of the susceptibility to develop AITD is attributed to genetic factors, while environmental factors contribute to 21 percent. The identified AITD susceptibility genes include immune-modulating genes, such as the major histocompatibility complex (MHC), cytotoxic T lymphocyte antigen-4 (CTLA-4), CD40 molecule, and protein tyrosine phosphatase-22 (PTPN22), and thyroid-specific genes, including TSH receptor (TSHR) and thyroglobulin (TG). The exact nature of the role environmental factors play in AITD is still not well known, but the involvement of several factors such as iodine diet content, stress, drugs and infections has been reported. However, there is no clear evidence of causality and the mechanisms by which environmental factors trigger thyroid autoimmunity in genetically predisposed individuals remain not fully understood. Knowledge of the precise mechanisms of interaction between environmental factors and genes in inducing thyroid autoimmunity could result in the development of new strategies for prevention and treatment.

Disfunções mínimas da tiróide: hipotiroidismo subclínico e hipertiroidismo subclínico / Subclinical thyroid disease: subclinical hypothyroidism and hyperthyroidism

Hipotiroidismo subclínico (SHT) e hipertiroidismo subclínico (SCH) são definidos pelas concentrações normais de T4 e T3 livres séricos associadas com valores de TSH elevado (SHT) ou suprimido (SCH). As prevalências são baixas e sintomas e sinais de disfunção tiroideana escassos. No SHT, colesterol total e LDL-C estão ligeiramente elevados, e tratamento com levotiroxina pode influir nos valores dos lipídeos. Ocorre diminuição da contratilidade do miocárdio e aumento da resistência vascular periférica, que melhoram com o tratamento. Fibrilação atrial é mais freqüente no SCH, e há aumento do índice de massa do ventrículo esquerdo, da contratilidade cardíaca, disfunção diastólica e indução de batimentos atriais ectópicos que regridem com uso de beta-bloqueadores. No SCH, ocorre diminuição da densidade óssea. Depressão, doença do pânico e alterações de testes cognitivos são freqüentes no SHT. O tratamento do SHT é indicado com TSH sérico maior do que 8mU/L e presença de anticorpos antitiroideanos, e do SCH endógeno, quando existem sintomas, em idosos ou concentração de TSH menor do que 0,1mU/L.

Reserva supra-renal na tuberculose pulmonar: resposta do cortisol sérico ao estímulo com ACTH de açäo prolongada / Adrenal reserve in pulmonary tuberculosis: serum cortisol response to stimulation with long-acting ACTH

Propusemo-nos a inveetigar a reserva supra-renal na tuberculose pulmonar utilizando ACTH-DEPOT, intramuscular, que resulta em estímulo mais intenso e prolongado. Estudamos 32 pacientes com tuberculose pulmonar, recém-diagnosticados com baciloscopia positiva, sem tratamento ou com menos de uma semana de tratamento específico. O estímulo adrenal foi feito com colheita de cortisol plasmático em jejum (basal) e após 6 horas de administraçäo do ACTH-DEPOT. Os pacientes apresentavam cortisol basal de 21,4 +/-/- 6,9ng/dl, após estímulo (6 horas) de 54,3+/-/- 19ng/dl (p<0,001), incremento absoluto de 17,4 +/- 31ng/dl (NS)e incremento relativo de 171 +/-/- 92 por cento (p<0,01)em comparaçäo aos normais, respectivamente 13 +/-/- 5,2ng/dl; 52,4 +/-/- 10,4ng/dl; 39,2 +/-/- 21,7ng/dl e 429 +/-/- 478 por cento. Em relaçäo aos valores pós-estímulo e incremento absoluto, näo houve difernça nos dois grupos, mas o nível basal foi maior nos tuberculosos (p<0,001)e o incremento relativo maior nos normais (p<0,001). O menor incremento relativo na tuberculose podera ser explicado pelos níveis de cortisol basal mais elevados, do que pelo comprometimento granulomatoso da glàndula. Em conclusäo, apesar da diferença em relaçäo ao incremento relativo do cortisol nos pacientes tuberculosos, nenhum apresentou resposta compatível com reserva adrenal diminuída, demonstrando que mesmo na fase ativa o comprometimento funcional da glàndula näo é acentuado.

Tuberculose de intestino grosso / Large intestine tuberculosis

Os autores apresentam dois casos de tuberculose intestinal. Em um havia lesao pulmonar concomitante, e a patologia intestinal evoluiu para a perfuraçao que e uma forma incomum de apresentaçao da doença. No outro, havia lesao intestinal sem lesao pulmonar, o que tambem e bastante raro