leptin and Graves-Disease

Topics: Antithyroid Agents; Body Composition; Graves Disease; Humans; Leptin; Recurrence

Patients with Graves' thyrotoxicosis lose weight despite increased appetite and food intake, thus suggesting a disturbed balance between energy intake and expenditure. Underlying mechanisms are not fully elucidated. The objective of this study was to investigate whether hormonal factors, known to affect hunger/satiety, change significantly over time as pharmacological treatment turns hyperthyroidism into euthyroidism. For that purpose 11 patients with Graves' thyrotoxicosis were given thiamazole and l-thyroxine for 18-20 mo. They were investigated on three occasions: Test 1: before pharmacological therapy; Test 2: during medication; Test 3: a few months after conclusion of the pharmacological treatment. Sixteen healthy subjects were also investigated for comparison. The participants were fasted overnight. Blood samples for determination of plasma glucose and serum concentrations of free T3 and T4, TSH, albumin, cortisol, insulin, GH, IGF-1, IGFBP-1, leptin, and ghrelin were drawn in the morning from an antecubital vein. Laboratory data obtained in test 1 were statistically compared with those in tests 2 and 3. The study showed that the free T3 level declined from 42.8 +/- 4.3 pmol/L in test 1 to 6.0 +/- 0.8 pmol/L in test 2 (85 +/- 2% decline), and 5.5 +/- 0.3 pmol/L in test 3 (86 +/- 2% decline). The free T4 level fell concomitantly from 65.2 +/- 4.8 to 16.6 +/- 1.7 and 14.4 +/- 1.2 pmol/L. The glucose level was significantly higher during hyperthyroidism (test 1) than during euthyroidism (tests 2 and 3), whereas cortisol, insulin, GH, IGF-1, and leptin levels were similar. The IGFBP-1 level was initially high (48.8 +/- 8.5 microg/L in test 1), but with a relative decline in free T3 of 85 +/- 2% (test 2) the IGFBP-1 level declined by 34 +/- 13%, and with a free T3 decline of 86 +/- 2% (test 3) the binding protein fell by 39 +/- 29%. This brought about increased IGF-1 bioavailability as reflected by a rising IGF-1/IGFBP-1 ratio from 5.1 +/- 1.1 to 13.8 +/- 2.9 (p < 0.01). The ghrelin level was low (2454 +/- 304 ng/L) in test 1. It increased to 3127 +/- 397 ng/L in test 2 (p < 0.05), and to 3348 +/- 279 ng/L in test 3 (p < 0.01).. Both ghrelin secretion and IGF-1 bioavailability are low in patients with untreated thyrotoxicosis, but increase markedly as pharmacotherapy makes them euthyroid. These metabolic changes may be caused by the transition of hyperthyroidism into euthyroidism rather than by the pharmacotherapy per se, since the metabolic changes prevailed also in the posttreatment period.

Topics: Adolescent; Antithyroid Agents; Blood Glucose; Body Mass Index; Female; Ghrelin; Graves Disease; Hormones; Humans; Hunger; Insulin; Leptin; Long-Term Care; Male; Middle Aged; Peptide Hormones; Satiety Response; Thyroid Hormones

Hyperthyroidism is associated with altered growth hormone (GH) secretion. Many patients with thyroid dysfunction experience several poorly described complications such as symptoms and signs also seen in patients with growth hormone deficiency (GHD). We have therefore prospectively evaluated a possible relationship between the thyroid function, body composition, leptin levels and insulin-like growth factor (IGF) related peptides in patients with Graves' disease. DESIGN, PATIENTS, AND MEASUREMENTS: In a prospective group of 24 fasting female patients with Graves' disease (mean age (CI 95%): 40 years (33-47)), we measured serum thyroxine, triiodothyronine, thyrotropine (TSH), TSH receptor antibodies, anti-thyroid peroxidase, leptin, body composition, body mass index (BMI) and IGF-related peptides at diagnosis and after 12 months of treatment with thiamazol (ATD).. In thyrotoxic patients IGF-I plus IGF-II correlated positively with IGFBP-3 at baseline (r = 0.90, p < 0.1 x 10(16)) and after 12 months follow-up (r = 0.87, p < 0.1 x 10(-16)). In the thyrotoxic state total IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and acid-labile subunit (ALS) but not free IGF-I decreased significantly from 223 microg/L (189-260) (mean (CI 95%), 877 microg/L (801-953), 4165 microg/L (3772-4577) and 22 mg/L (18-26)) to 198 microg/L (172-226), 788 microg/L (711-865), 3431 microg/L (3135-3741) and 19 mg/L (16-26) (p <0.006), respectively, after 12 months of ATD despite an increase in BMI from 22 (21-23) to 23 kg/m(2) (22-25) (p < 0.0004) but no significant changes in leptin.. The complex IGF systems seemed intact in thyrotoxic patients but change in body composition and the regulation of leptin and insulin secretion during treatment of autoimmune thyroid disease influence IGF-related peptides leaving the patient in a state somewhat similar to partial GHD, but the mechanism behind these alterations remains unclear.

Topics: Adult; Body Composition; Female; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Iodide Peroxidase; Leptin; Male; Methimazole; Middle Aged; Somatomedins; Thyroid Hormones; Thyrotoxicosis

Autoimmune thyroid diseases (AITDs), predominately Graves׳ disease and Hashimoto׳s thyroiditis, comprise the most common autoimmune diseases in humans. Both have the production of anti-thyroid antibody as an important aspect and both are much more prevalent in females, being at least 10 times more common than in males. Using these two clues, a hypothesis for the initiation of thyroid autoimmunity is proposed that helps to make the case that the thyroid is one of the most sensitive sites for autoimmunity and helps account for the prevalence and the observed sex differences in AITDs and associated diseases, such as type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). The primary mechanisms proposed involve the underlying state of inflammation as a result of the adipokines, especially leptin, TNF-α, and IL-6, and the receptors able to recognize pathogen-associated molecular patterns (PAMP׳s) and damage-associated molecular patterns (DAMP׳s) through Toll-like receptors (TLR) and others receptors present on thyrocytes. The adipokines are produced by adipose tissue, but have hormone-like and immune modulating properties. As the levels of leptin are significantly higher in females, an explanation for the sex difference in thyroid autoimmunity emerges. The ability of the thyrocytes to participate in innate immunity through the TLR provides an adjuvant-like signal and allows for the action of other agents, such as environmental factors, viruses, bacteria, and even stress to provide the initiation step to break tolerance to thyroid self-antigens. Seeing the thyroid as one of the most sensitive sites for autoimmunity, means that for many autoimmune disorders, if autoimmunity is present, it is likely to also be present in the thyroid - and that that condition in the thyroid was probably earlier. The evidence is seen in multiple autoimmune syndrome.

Topics: Adipokines; Animals; Autoantibodies; Autoantigens; Autoimmunity; Diabetes Mellitus, Type 1; Female; Graves Disease; Hashimoto Disease; Humans; Immunity, Innate; Inflammation; Leptin; Male; Mice; Prevalence; Receptors, Pattern Recognition; Sex Factors; Thyroid Gland

There is insufficient information about the appetite-related hormones orexin-A, nesfatin-1, agouti-related peptide (AgRP), and neuropeptide Y (NPY) in hyperthyroidism. The aim of the present study was to investigate the effects of hyperthyroidism on the basal metabolic rate (BMR) and energy intake, orexin-A, nesfatin-1, AgRP, NPY, and leptin levels in the circulation, and their relationship with each other and on appetite.. In this prospective study, patients were evaluated in hyperthyroid and euthyroid states in comparison with healthy subjects. Twenty-one patients with overt hyperthyroidism and 33 healthy controls were included in the study.. Daily energy intake in the hyperthyroid state was found to be higher than that in the euthyroid state patient group (p=0.039). BMR was higher in hyperthyroid patients than the control group (p=0.018). Orexin-A was lower and nesfatin-1 was higher in hyperthyroid patients compared to the controls (p<0.001), whereas orexin-A increased and nesfatin-1 decreased after euthyroidism (p=0.003, p<0.001). No differences were found in the AgRP, NPY, and leptin levels between the hyperthyroid and euthyroid states and controls (p>0.05). Orexin-A correlated negatively with nesfatin-1 (p=0.042), BMR (p=0.013), free triiodothyronine (fT3; p<0.001), and free thyroxine (fT4; p<0.001) and positively with thyrotropin (TSH; p<0.001). Nesfatin-1 correlated negatively with orexin-A (p=0.042) and TSH (p<0.001) and positively with fT3 (p=0.005) and fT4 (p=0.001). In the regression analysis, "diagnosis of hyperthyroidism" was the main factor affecting orexin-A (p<0.001).. Although it seems that no relationship exists among orexin-A, nesfatin-1, and increased appetite in hyperthyroidism, the orexin-A and nesfatin-1 levels are markedly affected by hyperthyroidism.

Topics: Adult; Agouti-Related Protein; Appetite; Basal Metabolism; Calcium-Binding Proteins; Case-Control Studies; DNA-Binding Proteins; Energy Intake; Female; Graves Disease; Humans; Hyperthyroidism; Leptin; Longitudinal Studies; Male; Middle Aged; Nerve Tissue Proteins; Neuropeptide Y; Nucleobindins; Orexins; Prospective Studies; Thyrotropin; Thyroxine; Triiodothyronine; Young Adult

Acquired generalized lipodystrophy (AGL) is associated with leptin deficiency as a result of adipose tissue loss and hypertriglyceridemia, insulin resistance, and hepatic steatosis. It may coexist with other autoimmune diseases such as Hashimoto's thyroiditis, rheumatoid arthritis, hemolytic anemia, and chronic active hepatitis. Metreleptin therapy has been shown to improve metabolic abnormalities in lipodystrophy, but the effect on AGL patients with active autoimmune disease is unknown.. We report 3 cases of pediatric patients with AGL and distinct active autoimmune diseases who were treated with metreleptin over a period of 4-6 years. Case 1 is a 9-year-old girl with active juvenile dermatomyositis, who was successfully treated with leptin with no worsening of her dermatomoysitis. Case 2 is a 16-year-old female with Graves' disease, who could discontinue all her antidiabetic medication completely with improved triglyceride levels. Case 3 is an 11-year-old boy with active autoimmune hepatitis and chronic urticaria, whose hyperphagia has resolved and his liver enzymes and hepatosplenomegaly have improved.. Metreleptin therapy is of considerable clinical benefit to reduce insulin resistance and hypertriglyceridemia and did not appear to alter the clinical course of autoimmune disease nor clinical efficacy of immunosuppressive treatments. Our observations suggest that risk or presence of autoimmune disease should not lead to withholding of metreleptin treatment from patients with AGL, but should prompt close clinical follow up in light of cautionary preclinical data.

Topics: Adolescent; Autoimmune Diseases; Child; Compassionate Use Trials; Dermatomyositis; Female; Graves Disease; Hepatitis, Autoimmune; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Leptin; Lipodystrophy; Male; Severity of Illness Index; Treatment Outcome; Urticaria

Leptin, adiponectin and resistin, mainly produced by adipocytes, play a major role in body weight regulation. Disturbances in the maintenance of normal body weight are found to occur also in thyroid diseases. There is a close relationship of the changes in thyroid hormones with the contents of adipose tissue and adipocyte-secreted proteins regulating energetic metabolism in the body. The study objective was to analyze the levels of leptin, adiponectin and resistin in children with untreated Graves' disease, subclinical hypothyroidism in Hashimoto's thyroiditis and in children with simple goiter. The study involved 78 patients with Graves' disease (29 girls and 2 boys, aged 6-21 years, mean 15.2) and with Hashimoto's thyroiditis (30 girls and 2 boys, aged 9-18 years, mean 14.5). The control group consisted of adolescents with simple goiter (13 girls and 2 boys, aged 9-18 years, mean 14.8). The levels of leptin, adiponectin and resistin were determined using the ELISA method (R&D System, USA). Patients with untreated Graves' disease showed higher adiponectin level than the patients with hypothyroidism in Hashimoto's thyroiditis and in simple goiter (14.24 +/- 0.89 vs. 9.18 +/- 2.65, 10.15 +/- 2.5, p < 0.007, p < 0.01), but lower resistin level as compared to simple goiter and Hashimoto's thyroiditis (10.24 +/- 5.2 vs. 13.29 +/- 3.8, 12.2 +/- 2.8, p < 0.01, NS). The analysis of leptin levels revealed no significant differences between children with subclinical hypothyroidism and untreated Graves' disease (4.42 +/- 0.87 vs. 3.1 +/- 0.45 NS). In conclusion, we suggest that disturbances in thyroid hormones in thyroid diseases have an essential effect on the levels of adiponectin and resistin released by adipose tissue.

Topics: Adiponectin; Adipose Tissue; Adolescent; Body Weight; Child; Enzyme-Linked Immunosorbent Assay; Female; Goiter; Graves Disease; Hashimoto Disease; Humans; Leptin; Male; Resistin; Statistics, Nonparametric; Thyroid Hormones; Young Adult

The signs and symptoms of Graves' ophthalmopathy (GO) result from increased volume of the orbital contents, including adipose, connective, and extraocular muscle tissues. We wanted to determine whether the expanded adipose tissue volume might be in part attributable to de novo adipogenesis. We measured levels of mRNA encoding leptin, adiponectin, peroxisome proliferator-activated receptor gamma (PPAR gamma), preadipocyte factor-1, and TSH receptor (TSHr) genes in orbital adipose tissues from GO patients (n = 22) and normal individuals (n = 18) and in orbital preadipocyte cultures derived from GO patients (n = 6) and normal subjects (n = 3) using quantitative real-time RT PCR. We found increased leptin, adiponectin, PPAR gamma, and TSHr expression in GO compared with normal orbital tissue samples, with positive correlations in the GO tissues between TSHr and leptin, adiponectin and PPAR gamma. In vitro differentiation of GO and normal preadipocytes resulted in enhanced adiponectin, leptin, and TSHr expression, with greater expression of the latter two genes in the GO cultures. These results suggest that de novo adipogenesis within orbital tissues with parallel enhanced expression of TSHr may be important in the pathogenesis of GO, and that potential therapies for GO might include inhibition of the adipogenic pathway.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Case-Control Studies; Cell Differentiation; Cells, Cultured; Graves Disease; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Orbit; Proteins; Receptors, Cytoplasmic and Nuclear; Receptors, Thyrotropin; RNA, Messenger; Stem Cells; Transcription Factors

Thyroid hormones as well as the recently discovered secretory products of adipose tissue adiponectin and resistin take part in energy metabolism. To study the changes in the adipocyte hormones with changes in the thyroid functional status, we measured adiponectin, resistin, and leptin in 69 subjects with Graves' disease before and 32 patients at follow up after treatment for hyperthyroidism at hypothyroid state. Concentrations of serum adiponectin and resistin were higher in hyperthyroid state than in hypothyroid state (adiponectin: 5.73 +/- 1.1 vs. 3.0 +/- 0.5 ng/ml, P = 0.03) (resistin: 6.378 +/- 0.6 vs. 5.81 +/- 0.57 ng/ml, P < 0.0001). Resistin levels correlate positively with free t4(r = 0.37, P < 0.01), free t3 levels(r = 0.33, P < 0.01) and negatively with TSH(r = -0.22, P < 0.05). Adiponectin levels correlate with free t4(r = 0.33, P < 0.01) and free t3 (r = 0.44, P < 0.01). Though the adiponectin levels did not correlate with leptin or resistin levels, strong positive correlation of both resistin and adiponectin with thyroid hormones is noted. Serum levels of leptin did not change with change in the thyroid functional status (leptin: 53.38 +/- 2.47 vs. 55.10 +/- 2.58 NS). Leptin levels did not correlate with resistin and adiponectin. We conclude that thyroid function has effect on adipocyte hormones adiponectin and resistin but not leptin.

Topics: Adipocytes; Adiponectin; Graves Disease; Hormones, Ectopic; Humans; Hyperthyroidism; Intercellular Signaling Peptides and Proteins; Leptin; Resistin; Thyroid Gland

This study was designed to investigate adipose tissue secretion of interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism.. We studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for Graves' hyperthyroidism and 16 healthy, euthyroid control subjects.. Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF-alpha and PAI-1 were analysed. Subcutaneous fat biopsies were taken for subsequent measurement of IL-6, leptin, TNF-alpha and PAI-1 protein secretion.. In patients with Graves' disease, the anti-thyroid treatment resulted in significant reductions of plasma thyroxine and triiodothyronine levels. No differences in serum concentration or adipose tissue secretion of leptin or TNF-alpha were observed either before, as compared with during, anti-thyroid treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1 activity, but not adipose tissue secretion of PAI-1, was increased both in Graves' disease before as compared with during anti-thyroid treatment (P=0.01) and in thyrotoxic patients compared with euthyroid controls (P=0.0001). Finally, adipose secretion of IL-6 was increased both before (8-fold, P=0.001) and during (6-fold, P<0.0001) treatment as compared with control subjects. Accordingly, serum concentration of IL-6 was also increased by about 50% in thyrotoxic patients as compared with healthy controls (P=0.03).. In Graves' hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6, but not of leptin, TNF-alpha or PAI-1, is markedly increased in comparison with euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate adipose tissue release of IL-6.

Topics: Adipose Tissue; Adult; Antithyroid Agents; Female; Graves Disease; Humans; Interleukin-6; Leptin; Plasminogen Activator Inhibitor 1; Reference Values; Thyroxine; Triiodothyronine; Tumor Necrosis Factor-alpha

Graves' ophthalmopathy (GO) is an autoimmune disease characterized by an increase in the volume of the orbital fatty/connective tissues and extraocular muscles. This volume change is due to expansion of the adipose tissues and to accumulation of glycosaminoglycans and edema within the connective tissues of the orbit. We have shown previously that a subpopulation of confluent human orbital preadipocyte fibroblasts can be induced in vitro to differentiate into cells with morphological features of adipocytes and that these cultures express functional thyrotropin receptor (TSHR). In order to identify and study these cells further, we examined the expression of leptin protein and TSHR and leptin mRNA in these cultures. Using immunocytochemistry with objective measurement of immunofluorescent staining intensity on digitized microscopic images, we determined leptin protein expression to be 6 to 37 times greater in differentiated cultures than in control cultures. In addition, we showed that the expression of both genes is enhanced in differentiated cultures. We suggest that an unknown humoral stimulus, present in Graves' disease, might act to induce the differentiation of normal orbital fibroblasts into TSHR-bearing adipocytes. This process would be expected to result in expansion of the orbital adipose tissues and increased TSHR expression within the orbit.

Topics: Adipocytes; Cell Differentiation; Cells, Cultured; Fibroblasts; Fluorescent Antibody Technique; Gene Expression; Graves Disease; Humans; Leptin; Orbit; Receptors, Leptin; Receptors, Thyrotropin; RNA, Messenger; Stem Cells

In this study it was of interest to investigate the relationship between plasma leptin levels and thyroid function in recently diagnosed 27 Basedow-Graves patients and 22 multinodular goiter patients brought to euthyroid state with 1 mo of propylthiouracil (PTU) treatment. A group of 15 control subjects matched for age, gender, and body mass index were also studied. In Basedow-Graves patients there were significantly higher T4 and T3 levels accompanied by a marked fall in plasma thyroid-stimulating hormone (TSH). In multinodular goiter patients with PTU, the plasma T3 and T4 levels were significantly lower than in Basedow-Graves and TSH was markedly higher. However, TSH values in multinodular goiter patients were signifcantly lower than the control Plasma leptin levels were unchanged in all groups. These data suggest that leptin levels are not affected by thyroid dysfunction.

Topics: Adult; Female; Graves Disease; Humans; Leptin; Male; Middle Aged; Thyroid Function Tests; Thyroid Hormones

Whether leptin, a product of the ob gene, can be stimulated by glucocorticoid administration has been an issue of controversy. We investigated the effect of intravenous administration of methylprednisolone (500 mg/day x 3 days) on plasma levels of leptin in 16 patients (female/male = 11/5) with Graves' hyperthyroidism and active ophthalmopathy who received pulse therapy. Significant elevation of plasma leptin levels started at the eighth hour (13.9+/-1.8 ng/mL, p=0.042) and lasted until the 72nd hour (21.2+/-5.0 ng/mL, p=0.009), as compared with basal levels (8.8+/-1.2 ng/mL). When methylprednisolone was replaced with oral prednisolone (10 mg three times per day x 2 weeks), no difference in plasma leptin levels was noted compared with basal measurement. Under methylprednisolone administration, a significant suppression of tumor necrosis factor-alpha began at the 24th hour (8.1+/-1.3 pg/mL, p=0.004) and lasted until the 48th hour (8.1+/-1.0 pg/mL, p=0.008), as compared with basal measurement (12.5+/-1.5 pg/mL). Compared with basal levels (93+/-2 mg/dL), significant elevation in the plasma glucose level started at the third hour (135+/-10 mg/dL, p=0.000) and lasted until the 72nd hour (110+/-4 mg/dL, p=0.019). The timing of serum insulin elevation approximated that of plasma glucose (3 hours: 14+/-3 microU/mL, p=0.006) and lasted until the end of prednisolone administration (2 weeks: 12+/-2 microU/mL, p=0.044), when compared with basal levels (14+/-3 microU/mL). We concluded that the parental administration of pharmacological doses of methylprednisolone to patients with Graves' hyperthyroidism could acutely raise their plasma level of leptin.

Topics: Adult; Aged; Blood Glucose; Eye Diseases; Fatty Acids, Nonesterified; Female; Graves Disease; Humans; Injections, Intravenous; Insulin; Kinetics; Leptin; Lipids; Male; Methylprednisolone; Middle Aged; Prednisolone; Tumor Necrosis Factor-alpha

Leptin is a protein product of the ob gene, mainly produced by adipocytes. Leptin is thought to play an important role in the homeostasis of body weight by suppressing appetite and increasing energy consumption. The aim of this study was to investigate the possible effect of thyroid hormone on the regulation of the leptin system during suppression of beta-adrenergic receptors in Graves' patients. We studied 15 adult female patients with Graves' disease. Thyroid function, serum levels of leptin, and percent body fat (%BF) were examined at four different clinical conditions during therapy (A, untreated; B, beta-adrenergic antagonist only [A, B; hyperthyroid], C, beta-adrenergic antagonist and antithyroid drug; D, antithyroid drug only [C, D; euthyroid]). The use of beta-adrenergic antagonist significantly reduced heart rate in spite of hyperthyroid state, indicating sufficient suppression of beta-adrenergic receptors. During treatment with beta-adrenergic antagonist, leptin percentage of body fat (%BF) ratio significantly decreased in euthyroid state compared to that in hyperthyroid state (from 38.7 +/- 21.3 to 18.1 +/- 19.3, p = 0.003). Moreover, there was a significantly positive correlation between delta leptin/%BF and delta free thyroxine (FT4) (r = 0.51, p = 0.008). Under a euthyroid state induced by antithyroid drug treatment, leptin/%BF did not change in spite of withdrawal of beta-adrenergic antagonist. Our data indicate that thyroid hormones could increase serum leptin level during suppression of beta-adrenergic receptors in Graves' patients. Our data also suggest that the beta-adrenergic action of thyroid hormones might be partly mediated by regulation of leptin.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Female; Graves Disease; Humans; Leptin; Middle Aged; Thyroxine

We investigated whether thyroid status modulates serum leptin concentrations and body composition as determined by bioelectric impedance analysis (BIA). The percent body fat mass (%FM) in male Graves' disease was significantly lower than that in age- and sex- matched normal subjects, at the levels of 11.4+/-6.4% (mean+/-SD) vs 19.9+/-9.2% for men (n=12, P<0.05) but not for women (22.6+/-7.6% vs 24.9+/-13.1%, n=28). In contrast, in female hypothyroidism (n=11) %FM was significantly higher than that in normal subjects (32.9+/-11.5%, P<0.01). Among other body composition parameters, the percentage of body water (%BW), and lean body mass (LBM) were significantly lower in hypothyroid patients, and the ECM (extracellular mass)/BCM (body cell mass) ratio was significantly (P<0.0001) increased in Graves' disease which was the result of marked depletion of BCM with concomitant expansion of ECM. The serum leptin levels were significantly decreased in male Graves' patients (2.3+/-0.7 ng/ml, P<0.05), whereas in female Graves' patients (8.8+/-5.9 ng/ml) and patients with hypothyroidism (9.5+/-7.6 ng/ml), the levels were not different from those of normal controls matched for BMI or %FM. There was a positive correlation between serum leptin levels and %FM in female Graves' patients (r=0.635, P=0.001) and in hypothyroid patients (r=0.801, P=0.014) but not in male Graves patients. There was no significant relationship between serum leptin levels and thyroid hormones, TRAb, or TSAb. In euthyroid obese subjects there was a positive relationship between serum leptin levels and serum TSH levels (r=0.37, P<0.01). These results suggest that hyperthyroidism is characterized by the decreased fat mass and serum leptin levels in men, but female patients appear to be resistant to the effect of thyroid hormones. Together with previous reports, thyroid status has a minor role in the regulation of serum leptin levels.

Topics: Adult; Autoantibodies; Body Composition; Body Mass Index; Body Water; Electric Impedance; Female; Graves Disease; Humans; Hypothyroidism; Immunoglobulins, Thyroid-Stimulating; Leptin; Male; Middle Aged; Receptors, Leptin; Receptors, Thyrotropin; Thyroid Hormones; Thyrotropin

Previous studies of leptin in thyrotoxic human subjects have been short-term and cross-sectional. We have measured serum leptin concentrations in thyrotoxic patients in order to study the influence of endogenous thyroid hormones on the relationship between serum leptin and fat mass. DESIGN PATIENTS, MEASUREMENTS: In 10 fasting thyrotoxic patients (8 females, 2 males, mean age: 51 years) we measured serum leptin (microgram/l), total thyroxine (TT4), total triiodothyronine (TT3), thyrotropin (TSH) and by Dual Energy X-ray Absorptiometry (DEXA) total fat mass (TFM, kg) at time of diagnosis (0 months, baseline) and during 12 months treatment with thiamazole. For comparison 16 fasting thiamazole-treated euthyroid patients (14 females, 2 males, mean age: 38 years) were studied after one year follow-up (26 months (15-48)) and 18 normal controls (12 females, 6 males, mean age: 39 years).. The serum leptin concentration was 9.1 (1.3 micrograms/l (mean (SEM) in the thyrotoxic patients and increased significantly to 16.0 (1.3 micrograms/l (P < 0.0005) after 12 months treatment compared to both normal subjects and their own baseline. There was a significant correlation between serum leptin concentration and TFM in the normal control group (r = 0.79, P < 0.00009), in the thiamazole-treated euthyroid group (r = 0.85, P < 0.00003) and in the baseline thyrotoxic group (r = 0.84, P < 0.002) but the serum leptin/TFM ratio increased significantly during 12 months of antithyroid drug treatment from 0.34 (1.2 micrograms/l/kg to 0.53 (1.2 micrograms/l/kg (P < 0.03).. The thiamazole-treated thyrotoxic patients increased their serum leptin concentrations during 12 months antithyroid drug treatment without a significant corresponding degree of changes in TFM as expected from normal controls. It is suggested that the metabolic state in thyrotoxic patients can influence the regulation of serum leptin concentrations without any associated changes in TFM.

Topics: Adult; Aged; Antithyroid Agents; Body Composition; Female; Follow-Up Studies; Graves Disease; Humans; Leptin; Male; Methimazole; Middle Aged; Proteins; Statistics, Nonparametric; Thyroid Hormones