Patrícia de Fátima dos Santos Teixeira

Lipid profile in different degrees of hypothyroidism and effects of levothyroxine replacement in mild thyroid failure

The aim of this study was to evaluate the lipid profile of patients with different degrees of hypothyroidism and the effect of levothyroxine replacement in subclinical hypothyroidism (SH). Initially, a cross-sectional study was performed with 226 participants [SH = 133 participants, manifest hypothyroidism (MH) = 23 participants, and euthyroidism (EU) = 70 participants]. The mean levels of atherogenic lipid variables were greater in MH than in SH and were greater in SH than in EU, although the differences between SH and EU did not reach statistical significance. The SH subgroup with greater serum thyrotropin (TSH) levels and that with positive antithyroperoxidase antibodies (TPO-Ab) had greater levels of triglycerides and of the atherogenic index Apo B/Apo A. A positive correlation exists between serum TSH and total cholesterol (rs = 0.167; P = 0.006), triglycerides (rs = 0.219; P < 0.001), and ApoB levels (rs = 0.205; P < 0.001). Eleven patients who received levothyroxine (L-T4) treatment and 15 patients who received placebo were reevaluated 1 year after TSH adjusted intervention. A fall in atherogenic variables was observed in the L-T4-treated group, with significance for total cholesterol (-20.0 vs +16.1 mg/dL in the placebo group) and LDL-c (-21.7 vs +17.2 mg/dL). We concluded that SH leads to an intermediary lipid profile between euthyroid individuals and that found in manifest hypothyroidism and that a significant lipid profile improvement occurred 1 year after L-T4 replacement therapy.

Subclinical hypothyroidism: psychiatric disorders and symptoms

OBJECTIVE To evaluate the prevalence of psychiatric disorders and symptoms in patients with subclinical hypothyroidism. METHOD Ninety-four outpatients with at least two elevated serum thyrotrophin levels (> 4 microU/ml) and normal FT4, and 43 euthyroid outpatients, both groups from HUCFF-UFRJ, were evaluated. Psychiatric diagnosis was based on the Structured Clinical Interview Diagnostic for the DSM-IV axis I (SCID-I/DSM-IV), the psychopathological symptoms on Hamilton anxiety and depression scales, and the Beck Inventory. RESULTS Our data showed an increased prevalence of psychiatric disorders in the subclinical hypothyroidism patients when compared to the euthyroid group (45.7% vs 25.6%; p = 0.025), mood disorders being the most frequent. The prevalence of depressive symptoms based on Becks Scale among subclinical hypothyroidism patients was about 2.3 times higher than among euthyroid ones (45.6% vs 20.9%, p = 0.006). Anxiety symptoms were also more frequent among subclinical hypothyroidism patients (87.0% vs 60.5%, p < 0.001), mainly clinical anxiety (44.6% vs 23.3%; p = 0.001). CONCLUSION Our results showed a significant association of subclinical hypothyroidism with psychiatric disorders and an increased frequency of subsyndromic depression and anxiety symptoms in subclinical hypothyroidism in relation to the euthyroid group.

Perceived Health Status of Women with Overt and Subclinical Hypothyroidism

Objective: The objective of this study was to investigate the health status of women with overt and subclinical hypothyroidism and relate it to the presence of clinical signs and symptoms of the disease. Subjects and Methods: A cross-sectional study was conducted on 232 women divided into 3 groups: overt hypothyroidism (n = 14); subclinical hypothyroidism (n = 152), and controls (n = 66). Health status was evaluated by the questionnaire SF-36, and the clinical signs and symptoms of hypothyroidism were assessed with the Billewicz scale modified by Zulewski. The Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni correction was applied to compare continuous variables between the groups. To assess the relationship between SF-36 domains and the clinical score, as well as SF-36 domains and serum thyroid-stimulating hormone levels, the Spearman correlation coefficient was calculated. Results: Patients with overt hypothyroidism presented systematically lower scores in all SF-36 domains (p < 0.05), both in relation to subclinical hypothyroidism patients and controls. This indicates a great dissatisfaction with health status in this group. Patients with subclinical hypothyroidism presented statistically lower scores in relation to controls with the exception of the role-emotional and bodily pain domains, where although they were not statistically significant, scores were clinically different. Highly negative correlations between SF-36 domains and the clinical score were observed in overt hypothyroidism (physical function r = –0.80, p < 0.01; bodily pain r = –0.74, p < 0.01). Conclusion: Overt hypothyroidism seemed to be associated with worse perception of health status, negatively associated with clinical score.

Effect of levothyroxine replacement on exercise performance in subclinical hypothyroidism

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-T4) replacement. The aim of the present study was to verify possible cardiopulmonary changes during exercise in patients with subclinical hypothyroidism on L-T4 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.kg.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.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.

Effect of hormone replacement on exercise cardiopulmonary reserve and recovery performance in subclinical hypothyroidism

Subclinical hypothyroidism (SH) patients present cardiopulmonary, vascular and muscle dysfunction, but there is no consensus about the benefits of levothyroxine (L-T₄) intervention on cardiopulmonary performance during exercise. The aim of the present study was to investigate the effects of L-T₄ on cardiopulmonary exercise reserve and recovery in SH patients. Twenty-three SH women, 44 (40-50) years old, were submitted to two ergospirometry tests, with an interval of 6 months of normalization of thyroid-stimulating hormone (TSH) levels (L-T₄ replacement group) or simple observation (TSH = 6.90 μIU/mL; L-T₄ = 1.02 ng/dL). Patients with TSH >10 μIU/mL were excluded from the study to assure that they would receive treatment in this later stage of SH. Twenty 30- to 57-year-old women with no thyroid dysfunction (TSH = 1.38 μIU/mL; L-T₄ = 1.18 ng/dL) were also evaluated. At baseline, lower values of gas exchange ratio reserve (0.24 vs 0.30; P < 0.05) were found for SH patients. The treated group presented greater variation than the untreated group for pulmonary ventilation reserve (20.45 to 21.60 L/min; median variation = 5.2 vs 25.09 to 22.45 L/min; median variation = -4.75, respectively) and for gas exchange ratio reserve (0.19 to 0.27; median variation = 0.06 vs 0.28 to 0.18; median variation = -0.08, respectively). There were no relevant differences in cardiopulmonary recovery for either group at baseline or after follow-up. In the sample studied, L-T₄ replacement improved exercise cardiopulmonary reserve, but no modification was found in recovery performance after exercise during this period of analysis.

Avaliação clínica e de sintomas psiquiátricos no hipotireoidismo subclínico

BACKGROUND: This investigation evaluated and correlated clinical, laboratorial aspects and psychiatric symptoms in sub clinical hypothyroidism (SH). METHODS: Cross sectional study involving 103 patients with SH and 60 subjects without thyroid disease. Clinical and psychiatric evaluation was respectively based on the Zulewski score and Hamilton A, Hamilton D and Beck questionnaires. Serum thyreotropin (TSH), (thyroxine) FT4 and (antithyroperoxidase) ATPO were measured in all participants. Analysis of continuums data was assessed by the Student t- test, for normally distributed data, and by the Mann- Whitney and Kruskal Wallis tests for non-parametric data. The c2, Fishers and Kruskal Wallis tests were used to study qualitative variables. Multivariate analyses were used to study confounding variables. RESULTS: Mean serum TSH level was 7.76 ± 2.9 µUI/mL in SH and 1.66 ± 0.6 µUI/mL in the group without thyroid disease (p=0.001). Mean serum T4L was slightly lower among patients with HS, and showed a negative linear correlation with TSH. Higher frequencies of abnormal clinical score (48.3 vs. 67.0%; p=0.02), depression self reported symptoms (20.5 vs. 44.2%; p=0.011) and anxiety symptoms (86.0 vs. 63.4%; p=0.004) occurred more frequently in SH. Frequency of psychiatric symptoms had a positive correlation with the clinical score and serum TSH. There was no association between the clinical and psychiatric findings and the etiology of SH, presence of ATPO, age or menopause. CONCLUSIONS: The study showed that SH was associated with clinical findings and with psychiatric symptoms. Clinical trials are required to evaluate possible improvement with levotiroxine.

Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism

Subclinical hypothyroidism (SHT) is a disease for which exact therapeutic approaches have not yet been established. Previous studies have suggested an association between SHT and coronary heart disease. Whether this association is related to SHT-induced changes in serum lipid levels or to endothelial dysfunction is unclear. The aim of this study was to determine endothelial function measured by the flow-mediated vasodilatation of the brachial artery and the carotid artery intima-media thickness (IMT) in a group of women with SHT compared with euthyroid subjects. Triglycerides, total cholesterol, HDL-C, LDL-C, apoprotein A (apo A), apo B, and lipoprotein(a) were also determined. Twenty-one patients with SHT (mean age: 42.4 +/- 10.8 years and mean thyroid-stimulating hormone (TSH) levels: 8.2 +/- 2.7 microIU/mL) and 21 euthyroid controls matched for body mass index, age and atherosclerotic risk factors (mean age: 44.2 +/- 8.5 years and mean TSH levels: 1.4 +/- 0.6 microIU/mL) participated in the study. Lipid parameters (except HDL-C and apo A, which were lower) and IMT values were higher in the common carotid and carotid bifurcation of SHT patients with positive serum thyroid peroxidase antibodies (TPO-Ab) (0.62 +/- 0.2 and 0.62 +/- 0.16 mm for the common carotid and carotid bifurcation, respectively) when compared with the negative TPO-Ab group (0.55 +/- 0.24 and 0.58 +/- 0.13 mm, for common carotid and carotid bifurcation, respectively). The difference was not statistically significant. We conclude that minimal thyroid dysfunction had no adverse effects on endothelial function in the population studied. Further investigation is warranted to assess whether subclinical hypothyroidism, with and without TPO-Ab-positive serology, has any effect on endothelial function.

Prevalence of goiter and thyroid nodular disease in patients with class III obesity

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 cm³; 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.

Serum Leptin in Overt and Subclinical Hypothyroidism: Effect of Levothyroxine Treatment and Relationship to Menopausal Status and Body Composition

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.

Effects of physical activity on body composition and fatigue perception in patients on thyrotropin-suppressive therapy for differentiated thyroid carcinoma.

BACKGROUND Subclinical thyrotoxicosis (scTox) may be associated with alterations in body composition and fatigue that can be possibly reversed with physical activity. The aim of the present study was to evaluate whether the systematic practice of physical activity improves lower extremity muscle mass and fatigue perception in patients with scTox. MATERIALS AND METHODS We studied 36 patients (2 men) with median age of 48.0 (43.0-51.0) years, body mass index of 27.4 (22.1-30.2) kg/m(2), thyrotropin <0.4 mU/L, and free thyroxine between 0.8 and 1.9 ng/dL and 48 control subjects (C group; 7 men). Patients were randomly divided in two groups according to the adherence to the exercise training: scTox-Tr (n = 19)-patients who adhered to the exercise intervention and scTox-Sed (n = 17)--patients who did not adhere to it. The C group did not participate in the randomization. The exercise training was supervised by a physical education instructor, and it was composed of 60 minutes of aerobic activity and stretching exercises, twice a week, during 12 weeks. In both groups, body composition was assessed (anthropometric method), and the Chalder Fatigue Scale was determined at baseline and after 3 months of intervention (scTox-Tr group) or observation (scTox-Sed group). RESULTS At baseline, patients with scTox had lower muscle mass and mid-thigh girth and more fatigue on the Chalder Fatigue Scale than euthyroid control subjects. The scTox-Tr group had an increase in muscle mass, reduction in the variables reflecting whole body fat, and lesser perception of fatigue during the exercise training period (p ≤ 0.05 for these parameters at the start and end of the exercise training period). CONCLUSIONS scTox is associated with lower muscle mass and mid-thigh girth and more fatigue. Physical activity training can partially ameliorate these characteristics. More studies are needed to determine what training program would be optimum, both in terms of beneficial effects and for avoiding potential adverse responses.