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Metabolic syndrome (MetS) and thyroid dysfunction are common in clinical practice. The objectives of this review are to discuss some proposed mechanisms by which thyroid dysfunctions may lead to MetS, to describe the bidirectional relationship between thyroid hormones (THs) and adiposity and finally, to resume a list of recent studies in humans that evaluated possible associations between thyroid hormone status and MetS or its clinical components. Not solely THs, but also its metabolites regulate metabolic rate, influencing adiposity. The mechanisms enrolled are related to its direct effect on adenosine triphosphate (ATP) utilization, uncoupling synthesis of ATP, mitochondrial biogenesis, and its inotropic and chronotropic effects. THs also act controlling core body temperature, appetite, and sympathetic activity. In a bidirectional way, thyroid function is affected by adiposity. Leptin is one of the hallmarks, but the pro-inflammatory cytokines and also insulin resistance impact thyroid function and perhaps its structure. MetS development and weight gain have been positively associated with thyroid-stimulating hormone (TSH) in several studies. Adverse glucose metabolism may be related to hyperthyroidism, but also to reduction of thyroid function or higher serum TSH, as do abnormal serum triglyceride levels. Hypo- and hyperthyroidism have been related to higher blood pressure (BP), that may be consequence of genomic or nongenomic action of THs on the vasculature and in the heart. In summary, the interaction between THs and components of MetS is complex and not fully understood. More longitudinal studies controlling each of all confounding variables that interact with endpoints or exposure factors are still necessary.

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Although muscle metabolism and exercise capacity seem to be affected in patients with subclinical hypothyroidism, there is little evidence indicating improvement of the exercise tolerance due to levothyroxine (L-T(4)) replacement. The aim of the present study was to verify possible cardiopulmonary changes during exercise in patients with subclinical hypothyroidism on L-T(4) replacement with a normal serum TSH for six months. Twenty-three patients with subclinical hypothyroidism were randomized into treated (no.=11) and untreated (no.=12) patients. A cardiopulmonary test was performed with a treadmill, using the modified Balke protocol. Heart rate, oxygen uptake, minute ventilation and other cardiopulmonary parameters were assessed at the 5th minute of exercise. FT4 levels increased while TSH normalized after hormone replacement. Oxygen uptake decreased significantly after hormone replacement (24.1+/-6.3 vs 17.1+/-4.2 ml x kg x min(-1); p=0.03).Minute ventilation also showed an enhanced performance in treated patients (28.0+/-8.1 vs 23.5+/-5.6 l x min(-1); p=0.03), as did the heart rate (128+/-17 vs 121+/-17 bpm; p=0.03). There were no changes in the untreated group. The results demonstrate that submaximal cardiopulmonary exercise performance improved after six months of TSH normalization and this improvement can help enhance the ability to carry out daily life activities in patients with subclinical hypothyroidism.

Objectives: To evaluate the prevalence of goiter and nodular disease in patients with class III obesity, and to correlate results with serum leptin levels and insulin resistance (IR) parameters. Subjects and methods: A cross-sectional study was performed to assess thyroid ultrasound (US) patterns, HOMA-IR, serum leptin, and TSH levels in obese patients and controls. Results: Thyroid volume was positively correlated with body mass index (BMI) (r = 0.240, p = 0.039) and with HOMA-IR (r = 0.329; p < 0.01). Thyroid US patterns were similar between groups. However, when data from the male group was considered, greater thyroid volume was detected in the obese group compared with controls (10.8 vs. 8.5 cm 3 ; p = 0.04). Also, nodules were more frequently detected (67% vs. 18%), as were nodules requiring FNAB (33.3% vs. 0%, p ≥ 0.05-0.09), in this group. Conclusion: Although IR did not correlate directly with the presence of nodules, the results support the hypothesis of a direct association between insulin resistance and thyroid volume. Arq Bras Endocrinol Metab. 2013;57(2):120-5 Keywords Obesity; insulin resistance; goiter; thyroid nodule RESUMO Objetivos: Avaliar a prevalência de bócio e doença nodular tireoidiana em pacientes com obesidade grau III e correlacionar os resultados com os níveis de leptina e parâmetros de resistência à ação da insulina (RI). Sujeitos e métodos: Estudo seccional foi desenvolvido realizando ultrassonografia (US) tireoidiana e níveis séricos de HOMA-IR e TSH nos pacien tes obesos e nos controles. Resultados: Volume tireoidiano foi positivamente correlacionado com índice de massa corporal (IMC) (r = 0,240, p = 0,039) e com HOMA (r = 0,329; p < 0,01). Volume tireoidiano e prevalência de doença nodular tireoidiana foram similares entre os grupos. Quando avaliado o subgrupo masculino, maiores volumes tireoidianos foram detectados no grupo dos obesos comparados aos controles (10,8 vs. 8,5 cm 3 ; p = 0,04), nódulos foram mais frequentes (67% vs. 18%), assim como nódulos com indicação de punção (33,3% vs. 0%, p ≥ 0,05-0,09). Conclusão: Embora RI não se correlacione diretamente com a presença de nódulos, os resultados suportam a hipótese da direta associação entre resistência à ação da insulina e volume tireoidiano. Arq Bras Endocrinol Metab.2013;57(2):120-5 Descritores Obesidade; resistência à insulina; bócio; nódulo da glândula tireoide

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Many studies have found clinical and metabolic alterations in subclinical hypothyroidism, however, there are disagreements about the benefits of levothyroxine therapy. The objective of the present study was to analyze the effects of 6 months of treatment on the lipid profile of patients with subclinical hypothyroidism. A randomized double blind, placebo-controlled clinical assay was conducted. Sixty patients were enrolled in stratified random allocation by TSH levels that generated similar groups in average: free thyroxine levels, lipid levels, age, clinical score, and sedentary. At 6 months, 18 patients in the levothyroxine and 20 in the placebo group were reevaluated and a fall in all atherogenic lipid variables was observed with treatment. The TC and LDL-c variations (-22.6+/-37.2 and -18.5+/-34.6 mg/dl, respectively) in the group that received LT4 were statistically different (p=0.023 and p=0.012) from those occurring in the placebo group (+7.3+/-37.1 and +14.7+/-40.6 mg/dl). Baseline characteristics associated with better improvement in the levels of TC and LDL-c were the presence of TPO-Ab, TSH levels >8.0 microUI/ml, Body Mass Index >or=25 kg/m2, and the presence of menopause. We concluded that treatment with dose-adjusted levothyroxine reduced atherogenic lipid levels in some patients. Further studies to determine the effects of LT4 replacement in specific subgroups of SH patients are still necessary, especially in patients with TSH <8.0 microUI/ml.

Objective: The aim was to evaluate the quality of life (HRQoL) in women with subclinical hypothyroidism (sHT) after 16 weeks of endurance training. Subjects and methods: In the first phase, a cross-sectional study was conducted in which 22 women with sHT (median age: 41.5 (interquartile range: 17.5) years, body mass index: 26.2 (8.7) kg/m 2 , thyroid stimulating hormone > 4.94 mIU/L and free thyroxine between 0.8 and 1.3 ng/dL were compared to a group of 33 euthyroid women concerned to HRQoL. In the second phase, a randomized clinical trial was conducted where only women with sHT were randomly divided into two groups: sHT-Tr (n = 10)-participants that performed an exercise program-and sHT-Sed (n = 10)-controls. Exercise training consisted of 60 minutes of aerobic activities (bike and treadmill), three times a week, for 16 weeks. The HRQoL was assessed by the SF-36 questionnaire in the early and at the end of four months. Results: Women with sHT had lower scores on functional capacity domain in relation to the euthyroid ones (77.0 ± 23.0 vs. 88.8 ± 14.6; p = 0.020). The sHT-Tr group improved functional capacity, general health, emotional aspects, mental and physical component of HRQoL after training period, while the sHT-Sed group showed no significant changes. Conclusion: After 16 weeks of aerobic exercise training, there were remarkable improvements in HRQoL in women with sHT.