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PURPOSE: Understanding the relationship between antithyroperoxidase antibodies (TPOAb) and carotid intima-media thickness (cIMT) could provide insights into the mechanisms linking thyroid autoimmunity and cardiovascular disease. We aimed to explore the association of multiple categories of TPOAb with the increased cIMT at baseline and at follow-up in participants from the ELSA-Brasil Study. METHODS: This prospective cohort study analyzed data from 9,264 participants (51.5 ± 8.9 years old, 55.9% women) without a history of cardiovascular disease. Fasting serum TPOAb levels were determined. Values of cIMT equal to or above one deviation standard of the sample's mean were classified as increased cIMT at baseline. The increased cIMT after the 8-year follow-up was calculated after excluding participants with increased cIMT at baseline. Multivariate analyses were done using binary logistic and Poisson regression models. RESULTS: The increased cIMT was prevalent in 14.3% of the participants at baseline and its development occurred in 16.8% participants during the cohort. After adjustment for all confounder variables, TPOAb detectability (OR = 1.84, 95%CI = 1.21-2.79), and low detectable (OR = 1.81, 95%CI = 1.18-2.75), high detectable (OR = 2.01, 95%CI = 1.29-3.11) and positive (OR = 1.70, 95%CI = 1.07-2.70) TPOAb were positively associated with increased cIMT at baseline. The associations of low and high detectable TPOAb and increased cIMT at baseline were consistent when excluding those with thyroid dysfunction. There was no statistically significant association between TPOAb levels and increased cIMT at follow-up (p > 0.05), neither for all sample nor for euthyroid individuals. CONCLUSION: Different levels of TPOAb, including its detectability, were associated with increased cIMT at baseline in the studied sample. We highlight that may be relevant to consider the levels of TPOAb detectability as possible marker of increased cardiovascular risk.

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PURPOSE: To assess the associations between TSH and free thyroxine (FT4) levels and decline in functional status in euthyroid older patients at risk of frailty. DESIGN: Longitudinal prospective study. METHODS: Participants from the geriatric outpatient clinic of a university hospital, who fulfilled the criteria for frailty or were at risk of frailty, were recruited. Only those euthyroid, defined by age-specific reference range of TSH, were included. Serum was collected during enrollment and at the third and sixth years of follow-up to assess the mean value of all follow-up levels of serum TSH and FT4. Functional status assessing activities of daily living (ADL) and instrumental ADL were evaluated using the Katz Index and the Health Assessment Questionnaire, respectively. Functional decline was defined by a positive variation in any of the applied scales in the absence of disagreement between the scales or if the patient was institutionalized. RESULTS: Of the 273 participants (72.5% females) enrolled (mean age 80 years old), 48 died and 102 presented functional decline at the end of follow-up (mean 3.6 ± 1.7 years). Each 0.1 ng/dL increase in baseline and mean follow-up serum FT4 levels increased the risk of functional decline by 14.1% and 7.7%, respectively. The risk of functional decline was 9 times greater with baseline FT4 levels in the fourth and fifth quintiles (p = 0.049) and 50% lower with baseline FT4 levels in the first quintile (p = 0.046). No association between TSH and the outcome was found. CONCLUSIONS: Higher and lower FT4 levels were, respectively, a risk and a protective factor for the decline in functional status in a cohort of euthyroid older adults at risk of frailty.

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ABSTRACT This position statement was prepared to guide endocrinologists on the best approach to managing thyroid disorders during the coronavirus disease (COVID-19) pandemic. The most frequent thyroid hormonal findings in patients with COVID-19, particularly in individuals with severe disease, are similar to those present in the non-thyroidal illness syndrome and require no intervention. Subacute thyroiditis has also been reported during COVID-19 infection. Diagnosis and treatment of hypothyroidism during the COVID-19 pandemic may follow usual practice; however, should avoid frequent laboratory tests in patients with previous controlled disease. Well-controlled hypo and hyperthyroidism are not associated with an increased risk of COVID-19 infection or severity. Newly diagnosed hyperthyroidism during the pandemic should be preferably treated with antithyroid drugs (ATDs), bearing in mind the possibility of rare side effects with these medications, particularly agranulocytosis, which requires immediate intervention. Definitive treatment of hyperthyroidism (radioiodine therapy or surgery) may be considered in those cases that protective protocols can be followed to avoid COVID-19 contamination or once the pandemic is over. In patients with moderate Graves' ophthalmopathy (GO) not at risk of visual loss, glucocorticoids at immunosuppressive doses should be avoided, while in those with severe GO without COVID-19 and at risk of vision loss, intravenous glucocorticoid is the therapeutic choice. Considering that most of the thyroid cancer cases are low risk and associated with an excellent prognosis, surgical procedures could and should be postponed safely during the pandemic period. Additionally, when indicated, radioiodine therapy could also be safely postponed as long as it is possible.

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This position statement was prepared to guide endocrinologists on the best approach to managing thyroid disorders during the coronavirus disease (COVID-19) pandemic. The most frequent thyroid hormonal findings in patients with COVID-19, particularly in individuals with severe disease, are similar to those present in the non-thyroidal illness syndrome and require no intervention. Subacute thyroiditis has also been reported during COVID-19 infection. Diagnosis and treatment of hypothyroidism during the COVID-19 pandemic may follow usual practice; however, should avoid frequent laboratory tests in patients with previous controlled disease. Well-controlled hypo and hyperthyroidism are not associated with an increased risk of COVID-19 infection or severity. Newly diagnosed hyperthyroidism during the pandemic should be preferably treated with antithyroid drugs (ATDs), bearing in mind the possibility of rare side effects with these medications, particularly agranulocytosis, which requires immediate intervention. Definitive treatment of hyperthyroidism (radioiodine therapy or surgery) may be considered in those cases that protective protocols can be followed to avoid COVID-19 contamination or once the pandemic is over. In patients with moderate Graves' ophthalmopathy (GO) not at risk of visual loss, glucocorticoids at immunosuppressive doses should be avoided, while in those with severe GO without COVID-19 and at risk of vision loss, intravenous glucocorticoid is the therapeutic choice. Considering that most of the thyroid cancer cases are low risk and associated with an excellent prognosis, surgical procedures could and should be postponed safely during the pandemic period. Additionally, when indicated, radioiodine therapy could also be safely postponed as long as it is possible.

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INTRODUCTION: Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial. OBJECTIVE: This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil. MATERIALS AND METHODS: After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience. RESULTS: The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH. CONCLUSION: Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values > 10 mU/L and for certain patient subgroups.

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INTRODUÇÃO: O hipotireoidismo subclínico (HSC), definido por concentrações elevadas do TSH em face de níveis normais dos hormônios tireoidianos, tem elevada prevalência no Brasil, particularmente entre mulheres e idosos. Embora um número crescente de estudos venha associando o HSC com maior risco de doença arterial coronariana e de mortalidade, não há ensaio clínico randomizado sobre o benefício do tratamento com levotiroxina na redução dos riscos e o tratamento permanece controverso. OBJETIVO: Este consenso, patrocinado pelo Departamento de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia e desenvolvido por especialistas brasileiros com vasta experiência clínica em tireoide, apresenta recomendações baseadas em evidências para uma abordagem clínica do paciente com HSC no Brasil. MATERIAIS E MÉTODOS: Após estruturação das questões clínicas, a busca das evidências disponíveis na literatura foi realizada inicialmente na base de dados do MedLine-PubMed e posteriormente nas bases Embase e SciELO - Lilacs. A força da evidência, avaliada pelo sistema de classificação de Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evidência disponível para cada questão e a experiência brasileira. RESULTADOS: Os temas abordados foram definição e diagnóstico, história natural, significado clínico, tratamento e gestação, que resultaram em 29 recomendações para a abordagem clínica do paciente adulto com HSC. CONCLUSÃO: O tratamento com levotiroxina foi recomendado para todos os pacientes com HSC persistente com níveis séricos do TSH > 10 mU/L e para alguns subgrupos especiais de pacientes.

INTRODUCTION: Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial. OBJECTIVE: This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil. MATERIALS AND METHODS: After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience. RESULTS: The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH. CONCLUSION: Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values > 10 mU/L and for certain patient subgroups.

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BACKGROUND: The relationship between thyroid status, including subclinical hypothyroidism (SH) and serum leptin is controversial or uncertain. Therefore we evaluated serum leptin in SH and overt hypothyroidism (OH) and determined the effects of levothyroxine (LT(4)) replacement on serum leptin in these disorders. METHODS: Serum leptin, thyrotropin (TSH), free thyroxine, insulin, glucose, and body composition parameters were compared in 55 SH, 20 OH, and 28 euthyroid (EU) pre- and postmenopausal women. In addition, the effect of LT(4) treatment on serum leptin in SH and OH was assessed. RESULTS: The mean +/- SD (median) serum leptin concentrations in the OH and SH groups were higher than in the EU group (35.1 +/- 27.2 [33.0] and 36.6 +/- 21.9 [30.6] ng/mL, respectively, vs. 23.2 +/- 19.3 [17.9] ng/mL, p = 0.011), but the difference was only significant in postmenopausal women. The body mass index (BMI), fat mass index (FMI), and the homeostasis model assessment-insulin resistance (HOMA-IR) index values were not different among these groups. In premenopausal women there was no correlation between leptin, BMI, or FMI and serum TSH levels (r(s) = 0.009, p = 0.474; r(s) = 0.043, p = 0.367; r(s) = 0.092, p = 0.232). In the postmenopausal women, the partial correlation coefficient between TSH and leptin was present, even when controlling for BMI (r(s) = 0.297, p = 0.042) and FMI (r(s) = 0.275, p = 0.050). LT(4) treatment was associated with a reduction of serum leptin concentrations in the OH group (p = 0.008). In SH group there were no differences between LT(4) replacement or no treatment, since a fall in serum leptin levels was detected in both SH subgroups, despite a more pronounced fall with LT(4) use. Treatment of the SH and OH groups with LT(4) did not influence HOMA-IR index or body composition. CONCLUSIONS: Serum leptin concentrations are elevated in postmenopausal women with SH or OH. A relationship between thyroid status and serum leptin is further supported by the fact that LT(4) treatment, to restore the EU status, reduced serum leptin levels in OH in the absence of significant effects on BMI. In women, hypothyroidism influences either leptin secretion or degradation and this effect is more pronounced in postmenopausal than in premenopausal women.

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No intuito de identificar as manifestações clínicas do hipotireoidismo subclínico (HS) durante o estresse físico e na recuperação, foram comparadas 15 portadoras de HS com 16 mulheres saudáveis através de um teste cárdio-pulmonar em esteira ergométrica. Análise das médias obtidas através do Mann-Whitney U Test. As pacientes obtiveram valores menores no pico do exercício para fração expirada de O2 (14,90 ± 1,05 x 16 ± 1,14 por cento; p = 0,014); na variação da pressão arterial sistólica (34,33 ± 17,92 x 52,50 ± 17,22; p = 0,009); na duração do exercício (8,83 ± 2,91 x 14,5 ± 5,63 min; p = 0,0005), na carga máxima de teste (11,6 ± 4,22 x 18,94 ± 5,45 por cento; p = 0,0004), além de tendências na razão de trocas gasosas e na freqüência cardíaca de pico. Entre o primeiro e o terceiro minutos de recuperação, houve uma redução média de 0,71 mmHg na pressão arterial diastólica para essas pacientes, comparado a 5,33 mmHg das mulheres saudáveis (p = 0,0009) (recuperação mais lenta). Pode-se inferir que o HS é capaz de causar disfunções cárdio-pulmonares, com maior sensibilidade para os parâmetros previamente citados.

In order to identify the characteristics of subclinical hypothyroidism (SH) during physical stress and its recovery, 15 SH patients and 16 healthy women were compared by a treadmill cardiopulmonary test. Means of variables were analyzed by the Mann-Whitney U test. Patients obtained lower values for peak expired fraction of O2 (14.90 ± 1.05 x 16 ± 1.14 percent; p = 0.014); systolic blood pressure variation (34.33 ± 17.92 x 52.50 ± 17.22; p = 0.009); exercise duration (8.83 ± 2.91 x 14.5 ± 5.63 min; p = 0.0005), maximal test load (11.6 ± 4.22 x 18.94 ± 5.45 percent; p = 0.0004), as well as tendencies in gas exchange ratio and peak heart rate. Between the first and the third recovery minutes, there was a reduction of only 0.71 mmHg in the diastolic blood pressure, whereas there was a 5.33-mmHg reduction to control group (p = 0.0009) (slower recovery of patients). It is presumable that SH may cause cardiopulmonary dysfunctions, with higher sensibility to the parameters previously cited.

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In order to identify the characteristics of subclinical hypothyroidism (SH) during physical stress and its recovery, 15 SH patients and 16 healthy women were compared by a treadmill cardiopulmonary test. Means of variables were analyzed by the Mann-Whitney U test. Patients obtained lower values for peak expired fraction of O2 (14.90+/-1.05 x 16+/-1.14%; p = 0.014); systolic blood pressure variation (34.33+/-17.92 x 52.50+/-17.22; p = 0.009); exercise duration (8.83+/-2.91 x 14.5+/-5.63 min; p = 0.0005), maximal test load (11.6+/-4.22 x 18.94+/-5.45%; p = 0.0004), as well as tendencies in gas exchange ratio and peak heart rate. Between the first and the third recovery minutes, there was a reduction of only 0.71 mmHg in the diastolic blood pressure, whereas there was a 5.33-mmHg reduction to control group (p = 0.0009) (slower recovery of patients). It is presumable that SH may cause cardiopulmonary dysfunctions, with higher sensibility to the parameters previously cited.

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