Serum leptin and lipids in patients with thyroid dysfunction.

This work was undertaken to examine the relationship between thyroid hormone and serum leptin concentration. This study included 368 Japanese female subjects (27 were affected with pretreatment hyperthyroidism, 68 with hyperthyroidism during treatment, 19 with pretreatment hypothyroidism, 57 with hypothyroidism during treatment and 197 euthyroid control subjects) and 60 control male subjects. In the control group, serum leptin levels in males were lower than those recorded in females (mean +/- SD; 4.6 +/- 4.1 vs 9.5 +/- 6.4 ng/ml, p < 0.001). The leptin values correlated well with body mass index (BMI) and body fat mass (BFM) in both control male and female subjects (p < 0.001 for each). The serum leptin levels in pretreatment female patients with hyperthyroidism were significantly lower than those in the pretreatment patients with primary hypothyroidism and control female subjects (6.4 +/- 3.0 vs 9.7 +/- 6.3, 9.5 +/- 6.4 ng/ml; p < 0.05, 0.02, respectively), but after adjusting for BMI and BFM, the difference was mainly due to the significantly different BMI and BFM. Furthermore, serum leptin did not change significantly during the treatment in hyper and hypothyroidism. There was no correlation between serum leptin and thyroid hormones or lipids levels in female patients with thyroid disorders. Adiposity and gender were the major determinants of leptin concentration, but thyroid hormones did not appear to play any relevant role in leptin synthesis and secretion in human.     

甲状腺功能紊乱患者血清瘦素水平分析

目的　探讨甲状腺功能紊乱患者血清瘦素水平变化及瘦素与垂体—甲状腺轴 (PTA)的关系。方法　对 40例Graves病 (GD)、30例甲状腺机能减退症 (甲减 )患者和 2 8名健康受试者的血清瘦素 (leptin)、游离三碘甲状腺原氨酸 (FT3 )、游离甲状腺素 (FT4 )、促甲状腺激素 (TSH)、体脂百分含量 ( %BF)进行检测 ,所有受检者体重指数 (BMI) <2 5kg/m2 。结果　对照组血清瘦素浓度为 ( 5 .38± 3.11)ng/ml ,GD组为 ( 6 .0 7± 2 .93)ng/ml ,两组比较 ,差异无显著性 ,甲减组为 ( 10 .41± 4.45 )ng/ml,与对照组比较显著升高。三组血清瘦素浓度均与其 %BF显著正相关。对照组瘦素与TSH正相关 ,与FT3 、FT4 无相关关系。GD组瘦素与TSH、FT3 、FT4 无相关关系。甲减组因大多数TSH值增高超出检测范围 ,未作瘦素与之的相关性比较 ,而瘦素与FT3 、FT4 呈负相关关系。结论　甲状腺激素可能通过影响体脂含量而调节瘦素水平 ,瘦素和PTA是共同维持机体能量稳态的两个相互关联的系统。     

Plasma leptin concentrations are related to body fat mass and gender but not to thyroid dysfunction

Leptin, a newly defined protein synthesized and secreted from fat cells in both animals and humans, has gained wide attention. Many studies have been conducted on its roles in the regulation of body fat storage, energy expenditure and body weight changes. Thyroid dysfunction is known to have influences on the above changes in humans and these changes may in turn lead to a variation in circulating leptin levels. In addition, a sex dimorphism of plasma leptin levels has been a constant finding in many studies. However, the relationship between body fat mass and gender to plasma leptin levels in patients with various thyroid dysfunction has been rarely discussed together. A total of 134 patients with various thyroid function status were included in this study (hyperthyroidism: n = 50, hypothyroidism: n = 24, and euthyroidism: n = 60). Plasma leptin concentrations were compared between different thyroid function groups, and compared with body fat mass and body mass index (kg/m2) to check if these two parameters affect the circulating leptin levels. There were no significant differences between plasma leptin concentrations in the different thyroid function groups (Mean +/- SD: hyperthyroidism: 8.5 +/- 5.4 ng/ml, range: 1.5-25.8; hypothyroidism: 8.4 +/- 4.7 ng/ml, range: 1.8-20.1, and euthyroidism: 7.3 +/- 4.5 ng/ml, range: 0.6-20.9). Rather, a significant gender difference was found, with female subjects having two-fold higher levels than males when all study subjects were encompassed (female: 8.8 +/- 4.9 ng/ml, range: 11.7-25.8 vs male: 4.1 +/- 2.1 ng/ml, range 0.6-8.1, p < 0.001) or when thyroid function status was analyzed separately (hyperthyroidism: female: 9.7 +/- 5.5 ng/ml vs male: 4.3 +/- 2.1 ng/ml, p < 0.001; hypothyroidism: female: 9.7 +/- 4.6 ng/ml vs male: 4.4 +/- 2.4 ng/ml, p = 0.015; and euthyroidism: female: 7.9 +/- 4.5 ng/ml vs male: 3.6 +/- 1.9 ng/ml, p = 0.013). Plasma leptin concentrations had strong correlation with body fat mass in both females (r = 0.47, p < 0.001) and males (r = 0.71, p < 0.001). Good correlation was also observed between plasma leptin concentrations and body mass index in females (r = 0.51, p < 0.001) and males (r = 0.78, p < 0.001). Plasma leptin concentrations were not different in thyroid dysfunction. A significant gender difference existed and a positive correlation between body fat mass and BMI to plasma leptin was observed.     

Circulating leptin and angiogenic factors in preeclampsia patients

Leptin, one of adipocytokines, plays a wide range of important roles in reproductive biology. We have previously reported that low hypo-adiponectinemia might be involved in the pathophysiology of overweight preeclampsia (PE) patients. Moreover, recent reports have underscored the importance of circulating angiogenic factors in the pathophysiology of PE. Here, we examined whether leptin in conjunction with adiponectin and/or angiogenic factors plays some role in the pathophysiology of PE. We performed a cross-sectional study in 34 PE patients and normal pregnancies matched for gestational age and body mass index as controls. We measured serum concentrations of leptin, adiponectin, the angiogenic factors vascular endothelial growth factor (VEGF), placental growth factor, and the soluble VEGF receptors sFlt-1 and sFlk-1. We observed that leptin levels in PE patients were significantly higher compared with those in controls, but did not observe significant differences between normal- and overweight patients in both groups. We also showed a significant negative correlation between leptin and adiponectin in controls, but not in PE patients. There was a significant correlation between leptin and sFlt-1 in PE patients, while there were significant differences of body mass index, mean blood pressure and proteinuria between high and low leptin/sFlt-1 ratio group in PE patients. Moreover, there was a significant difference of leptin level between IUGR and normal growth group in PE patients. These results suggest that the circulating increased leptin might be derived mainly from the placenta and regulated by the placental hypoxic condition, whereas adiponectin might be derived mainly from adipose tissue; and that leptin might play some role through insulin resistance, autonomic activation, or direct effect on endothelium with other angiogenic factors in pathophysiology of PE compared with the exaggerated release of adiponectin from adipose tissue.     

HIV and thyroid dysfunction

Human Immunodeficiency virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS) are associated with dysfunction of many endocrine organs and their axis. HIV infectivity leads to altered metabolism, poor oral intake and increased prevalence of weight loss and wasting which may have a role in thyroid dysfunction. Overt thyroid dysfunction occurs at similar rates as the general population while subclinical disease such as nonthyroidal illness (sick euthyroid syndrome), subclinical hypothyroidism and isolated low T4 levels are more frequent. Moreover, HAART therapy can complicate thyroid function further through drug interactions and the immune reconstitution inflammatory syndrome (IRIS). In this review we report the common thyroid dysfunctions associated with HIV before and after HAART therapy. We discuss presentation, diagnostic work up, treatment and follow up in each condition.     

Circulating soluble leptin receptor and free leptin index during childhood,puberty, and adolescence

Leptin is bound in human blood by a high affinity binding protein, which appears to be identical with the soluble leptin receptor (sOB-R). Using a ligand-mediated immunofunctional assay for the determination of serum sOB-R, we investigated its course during childhood, puberty, and adolescence in a large cohort of 581 healthy children and adolescents and a small group of 13 patients with anorexia nervosa. In the first years of life, sOB-R is detectable in remarkably high concentrations. Thereafter, a continuous decline of sOB-R levels was found. Consequently, correlation analyses demonstrated significant inverse relationships (P < 0.001) of sOB-R with age, IGF-I levels, pubertal stage, auxological and body composition parameters, as well as with leptin concentrations. Multiple regression analysis revealed that height, IGF-I, and age (only in girls) were independent predictors of sOB-R levels; these variables account for approximately 65% and 48% of the variation of sOB-R levels in boys and girls, respectively. The courses of age-dependent median values for the free leptin index (FLI, ratio between leptin and sOB-R levels) and for leptin levels were parallel in both genders. Correlation analyses demonstrated that in particular parameters of growth and sexual maturation are more closely related to the FLI than to leptin alone; this closer relationship is more pronounced among boys. Weight gains of patients with anorexia nervosa resulted in a significant increase in leptin and IGF-I levels (P < 0.01), whereas the median of sOB-R values decreased (P < 0.01). sOB-R and IGF-I levels were again significantly correlated (r = -0.55, P < 0.01). These findings suggest that high levels of sOB-R in emaciation may reflect an up-regulation of the sOB-R to suppress leptin action during energy deficiency. Furthermore, determinations of sOB-R and FLI are additional valuable tools to investigate the leptin axis during growth and sexual maturation.     

Amiodarone and thyroid dysfunction.

Amiodarone is a potent and widely used antiarrhythmic drug that bears a structural resemblance to thyroid hormones. The high iodine content of the drug determines that amiodarone induces changes in circulating concentrations of thyroid hormones, largely through inhibition of conversion of thyroxine (T(4)) to tri-iodothyronine (T(3)). Amiodarone treatment typically results in a rise in serum T(4), often to above the normal range, associated with a fall in circulating T(3). These biochemical changes are found in subjects who remain clinically euthyroid. In addition to changes in circulating thyroid hormones found in euthyroid subjects, overt thyrotoxicosis and hypothyroidism may complicate amiodarone treatment. Amiodarone-induced thyrotoxicosis is more common in areas of iodine deficiency, whereas hypothyroidism is more common in iodine-rich parts of the world.     

亚临床甲状腺功能异常与骨质疏松

亚临床甲状腺功能异常(STD)和骨质疏松是常见的内分泌疾病,主要发生在女性和老年人群中.甲状腺激素和促甲状腺激素可直接或间接影响骨代谢,导致骨密度发生变化.而STD患者体内这两种激素水平异常,提示STD和骨质疏松之间存在一定的联系.此外,外源性甲状腺激素替代治疗亦可影响骨代谢,导致骨密度下降和骨质疏松.因此,明确STD和骨质疏松之间的联系并采取适当干预措施对于预防STD患者发生骨质疏松有重要意义.     

Circulating leptin and adiponectin levels in patients with primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) has been associated with high cardiovascular morbidity and mortality; its pathogenesis is not fully understood. Moreover, many metabolic abnormalities are frequently present in patients with PHPT. Several substances (such as leptin and adiponectin) are secreted from adipocytes, which may contribute to regulate energy homeostasis and the development of cardiovascular diseases. We examined the relationship between leptin and adiponectin levels and metabolic disorders in 67 newly diagnosed never-treated patients with PHPT and in 46 healthy subjects (HS). Twenty (29.8%) patients with PHPT presented a metabolic syndrome (as defined by Adult Treatment Panel III criteria). Serum leptin and adiponectin levels in HS were 6.28 +/- 3.3 ng/mL (range, 1.7-19.2 ng/mL) and 6.65 +/- 1.7 microg/mL (range, 3.72-10.86 microg/mL), respectively. In all patients with PHPT, the mean leptin levels (34.28 +/- 20.4 ng/mL) were significantly higher than those of HS (P < .01) and, in particular, in PHPT patients with metabolic syndrome (52.63 +/- 31.2 ng/mL) and positively correlated with body mass index, waist circumference, and cholesterol. The mean adiponectin level was significantly lower (4.34 +/- 3.5 mug/mL) only in PHPT patients with metabolic syndrome (P < .005) and negatively correlated with waist circumference and fasting glucose. We concluded that increased serum level of leptin and decreased serum level of adiponectin coexist in patients with PHPT and may represent a pathogenetic factor for cardiovascular disease in this condition.     

Circulating leptin concentrations and ovarian function in polycystic ovary syndrome

OBJECTIVE: Polycystic ovary syndrome (PCOS) is characterized by ovarian dysfunction. Although the role of leptin in the control of reproduction is unclear, it may be involved in the control of ovulation. The aim of this cross-sectional study was to determine the relationship between circulating leptin concentrations, and anthropometric, metabolic and endocrine variables as well as to examine a possible role of leptin in ovarian dysfunction associated with PCOS. DESIGN: Prospective observational study. METHODS: Seventy-one subjects with PCOS and 23 body mass index (BMI)-matched control subjects were recruited from infertility clinics. The association between serum leptin concentrations and the above variables was measured outwith the luteal phase. A subgroup of 24 PCOS subjects underwent more frequent blood sampling to monitor follicular growth and ovulation. The association between variables was measured by univariate, multivariate and partial correlation analyses. RESULTS: Serum leptin concentrations were not different in subjects with PCOS and controls, and were strongly associated with BMI in both groups. Twelve patients ovulated during the study period. There was no significant difference in serum leptin concentrations between ovulatory and anovulatory subjects. The relationship between BMI and leptin was similar in both groups. CONCLUSION: The results indicated that circulating leptin concentrations relate principally to total body fat in subjects with PCOS and controls, and that this is not associated with the facility for follicular development and ovulation in these patients.     

Serum leptin and ghrelin levels in premenopausal women with stable body mass index during treatment of thyroid dysfunction.

BACKGROUND: There are potentially complex interrelationships between thyroid function, leptin, ghrelin, body mass index (BMI), and percentage of body fat (%BF). The goal of this study was to determine if normalization of thyroid status in premenopausal women with hyperthyroidism and hypothyroidism would be associated with changes in serum leptin and ghrelin in the absence of thyroid dysfunction treatment-associated changes in BMI and %BF. METHODS: The study was carried out in 47 selected premenopausal women: 17 with hyperthyroidism, 11 with hypothyroidism, and 19 healthy individuals who constituted the control group. Patients with thyroid dysfunction were selected for study if their BMI and %BF did not change after treatment of thyroid dysfunction. Subjects in the control group were selected on the basis of the age, BMI, and the %BF characteristics of the patients with thyroid dysfunction. Concentrations of free thyroxine (fT4), free triiodothyronine (fT3), thyrotropin, leptin, and ghrelin in serum were determined before and after treatment of thyroid dysfunction and in the control group. RESULTS: Serum leptin concentrations were similar in patients with hyperthyroidism and hypothyroidism before treatment and in normal subjects and did not change significantly after treatment of hyperthyroidism or hypothyroidism. Serum ghrelin concentrations were lower in patients with hyperthyroidism, and higher in patients with hypothyroidism than in the control group (hypothyroidism = 2345 (1157-7015) [median (range)], hyperthyroidism = 1205 (438-2914), control = 2398 (1542-4920), p < 0.05). CONCLUSIONS: In premenopausal women with hyperthyroidism or hypothyroidism, treatment of thyroid dysfunction that is not associated with changes in BMI or %BF does not influence serum leptin but does affect serum ghrelin. Thyroid status itself, in the absence of alterations in the BMI and %BF, has an important influence on circulating ghrelin but not leptin.     

Postpartum thyroid dysfunction.

Postpartum thyroid dysfunction (PPTD) refers to the syndromes of transient hyperthyroidism, transient hypothyroidism, or both, occurring sequentially in the first 12 months postpartum. Approximately 5 to 9% of women develop the disorder in this period. PPTD is most often subclinical but some women will experience symptoms such as lack of energy and depression in the hypothyroid phase. The thyroid gland, which normally enlarges during pregnancy, will remain enlarged or enlarge further in the postpartum period in a significant number of affected women, instead of returning to the prepregnancy size as in unaffected women. The gland is painless and histologically demonstrates lymphocytic infiltration. PPTD is strongly associated with the presence of antimicrosomal and/or antithyroglobulin antibodies, which occur in up to 76% of cases. Antibody activity tends to increase in the postpartum period and to peak at the time of onset of the disorder. TSH receptor antibodies are not seen and the gland has low radioiodine uptake, distinguishing PPTD from Graves' disease. The HLA associations are controversial, as is the role of dietary iodine. The etiology of PPTD is almost certainly immunological, reflecting the phenomenon of rebound from the relative immune tolerance of pregnancy. Detection of the disorder is important in order to reassure or treat those who are symptomatic and because PPTD may recur in subsequent pregnancies. In addition, up to one third of affected women will go on to develop permanent hypothyroidism 2 to 4 years later. The role of screening for PPTD remains to be clarified.     

Amiodarone-induced thyroid gland dysfunction

Of a population of 400 patients treated with amiodarone, 97 underwent thyroid function evaluation. Of these, 20 patients proved to be thyrotoxic and 16 hypothyroid. In thyrotoxic patients, symptoms developed 2 to 36 months after starting treatment with amiodarone, the most specific laboratory finding being a high total T3 (TT3). No antithyroid treatment proved useful. Thyroid function returned to normal 3 to 7 months after stopping amiodarone therapy. In the hypothyroid group, a high thyroid-stimulating hormone was the most specific laboratory finding. These patients were treated with substitute therapy with or without withdrawal of amiodarone. The iodine content of the thyroid gland in part of this population taking amiodarone was measured by in vivo x-ray fluorescence. Patients in whom thyrotoxicosis developed showed especially high iodine contents. During treatment with amiodarone, patients at high risk of thyrotoxicosis were recognized by increasing TT3 values and higher iodine thyroid levels. A reduction in maintenance dose should be considered in this specific population.