leptin and Thyroid-Diseases

The literature on thyroid autoimmunity has identified many potential factors at play for the initiation and progression of autoimmune thyroid diseases. These factors include genetic susceptibility, environmental factors, some drugs, iodine and selenium, infection, molecular mimics, and immune system defects. The sheer number of feasible factors makes sorting out the necessary agents from the fellow travelers difficult. In addition, many of these factors have the capability to interact-further confusing the picture. Another difficulty in interpreting these data is that most proposed mechanisms are not able to accomplish the triggering event in which the tolerance to self-antigens is actually overcome. In addition, some findings may be describing the conditions present after a disease is diagnosed and may be consequences of the disease rather than a cause. Recent description of the role of adipokines, which include leptin, tumor necrosis factor-alpha, and interleukin-6, in contributing to the inflammatory environment of the thyroid, along with the presence of thyroid Toll-like receptors for pathogen-associated patterns have the potential to deliver that necessary adjuvant signal to break tolerance, seen as necessary in animal autoimmune models. An additional factor, vitamin D. To describe the many factors at play in thyroid autoimmunity and how they interact.. Thyroid autoimmunity is the result of an interplay of factors, with adipokines produced by WAT and vitamin D providing immune modulating signals external to the thyroid, while thyrocyte innate responses to environmental conditions provide the necessary adjuvant signal. Shaping the response to be reactive to particular self-antigens and likelihood of a response are due to genetics and molecular mimics.

Topics: Autoimmune Diseases; Humans; Leptin; Thyroid Diseases; Thyroid Gland; Vitamin D

The identification and sequencing of the ob gene and its product, leptin, in 1994 opened new insights in the study of the mechanisms controlling body weight and led to a surge of research activity. Since its discovery, leptin has been the subject of an enormous amount of work especially within the fields of nutrition, metabolism and endocrinology. Leptin is accepted as an adipose signal, and even though the underlying mechanisms are not fully clarified, leptin, in addition to the thyroid hormones, is believed to be involved in regulation during the switch from the fed to the starved state. It is not clear whether leptin and the melanocortin pathways interact with the thyroid axis under physiological conditions other than during starvation or in response to severe illness, both states in which the hypothalamo-pituitary-thyroid axis may be severely suppressed. In addition to the suggested central relationship between leptin and thyroid hormones, there might also be a peripheral relationship although this effect is not clear. Both thyroid hormones and leptin might be involved in the adaptive thermogenesis through mitochondrial uncoupling proteins and heat production because both thyroxine and triiodothyronine are involved in the starvation-induced decrease in thermogenesis. Both rodent and human studies of leptin have failed to show any consistent relationship between thyroid function and serum leptin concentrations. However, leptin might have an important role in thyroid pathophysiology due to thyroid hormone involvement in thermogenesis and regulation of uncoupling proteins. In this review, we have focused on leptin in relation to thyroid pathophysiology.

Topics: Animals; Biological Transport; Body Composition; Brain; Humans; Leptin; Receptors, Cell Surface; Receptors, Leptin; Thermogenesis; Thyroid Diseases; Thyroid Gland; Thyroid Hormones

Topics: Endocrine System Diseases; Female; Humans; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Thyroid Diseases

Topics: Animals; Body Composition; Carrier Proteins; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Mice; Proteins; Rats; Receptors, Cell Surface; Receptors, Leptin; Thyroid Diseases; Thyroid Gland; Thyroid Hormones

The obese gene product--leptin (LEP)--is a hormone released from adipose tissue implicated in the regulation of nutritional state and energy balance. The aim of this study was to assess the relationship between plasma LEP levels and nutritional state, secretion of hormones of the hypothalamic-pituitary axis, and personality traits in patients with anorexia nervosa (AN). The study was performed in 22 women with AN aged 19.45 +/- 0.92 yrs, mean BMI of 15.48 +/- 0.29 kg/m2, 14 healthy women with normal body weight (NW), aged 29.71 +/- 2.4 yrs, mean BMI of 21.22 +/- 0.43 kg/m2, and 19 obese women without metabolic disorders (OTY), aged 34.5 +/- 2.65 yrs, mean BMI of 37.47 +/- 2.06 kg/m2. Hormone levels were measured with RIA test kits. Psychological examination was carried out by means of Gough-Helibrun's and Catell's personality tests. Body mass index (BMI) and body composition, i.e. body fat mass (BF) and body fat percentage (%BF) were determined with a DEXA instrument (Lunar Co., WI, USA). Absolute plasma LEP levels and the LEP/%BF index were lowest in patients with AN whereas LEP/BF index did not differ among AN, NW, and OTY groups (Table 1). In all groups, LEP levels were positively correlated with BMI, BF, and %BF (Table 2). Plasma neuropeptide Y (NPY), beta-endorphin (B-EP), and galanin (GAL) levels in AN were significantly higher than in NW and OTY groups (Table 3). Plasma GAL levels were positively correlated with LEP/BF and LEP/%BF in AN patients only. Moreover in the AN group, serum/plasma levels of insulin (I), insulin-like growth hormone-1 (IGF-1), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), and free triiodothyronine (fT3) were significantly lower, and levels of cortisol (F) significantly higher than in NW and OTY groups (Table 4). Plasma LEP levels in AN patients were positively correlated with IRI, IGF-1, free thyroxine (fT4), and FSH levels, and negatively correlated with thyrotrophin (TSH) levels. Personality traits in patients with AN were significantly correlated with hormone levels (Tables 5 and 6), BMI and body fat content (Table 6).. 1) Leptin secretion from adipose tissue is not related to the nutritional state. 2) High levels of NPY, beta-EP, and GAL in AN confirm that starvation is deliberate in these patients. Low LEP levels in AN may lead to secondary amenorrhea and thyroid function disorders, as well as enhanced cortisol and growth hormone secretion of hypothalamic origin. A positive correlation between levels of LEP and IGF-1 and IRI may reflect mechanisms preserving adipose tissue and protecting from hypoglycemia and insulin resistance. A positive correlation between LEP and fT4 levels suggests a tendency to energy-sparing under conditions of low energy intake. Lack of correlation between LEP and F levels apparently reflects peripheral cortisol resistance in AN. 3) Both undernutrition and abnormal hormone secretion (LEP, F, fT3, IGF-1, LH, E2) are related to social self-withdrawal, defensive attitudes, low self-esteem and high level of self-supervision in AN.

Topics: Adipose Tissue; Adult; Amenorrhea; Anorexia Nervosa; Female; Human Growth Hormone; Humans; Hydrocortisone; Hypothalamus; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Metabolic Diseases; Nutritional Status; Starvation; Thyroid Diseases

We investigated the possible correlation between the leptin concentration and the Zn/Cu ratio in the plasma of women with thyroid disorder. Forty women with hypothyroidism (n = 20) or hypothyroidism (n = 20) and 20 euthyroid controls were recruited. The results showed that the women with thyroid disorder (hypothyroidism or hyperthyroidism) had higher plasma leptin concentrations than the normal controls (p < 0.05). Moreover, the plasma leptin concentration had no correlation with plasma thyroid hormone levels in the separate groups, nor among all the participants considered together. A strong correlation (p < 0.005) between leptin and adiposity was only observed in euthyroid women. Plasma values of Zn and Cu and the Zn/Cu ratio were not markedly different among women with altered thyroid status. However, a weak correlation (r = 0.28, p = 0.032) between leptin and the Zn/Cu ratio was found from the pooled data of all participants and retained after adjustment for adiposity. We suggest that there may exist an interaction between the plasma leptin level and thyroid hormone-induced abnormality for selected minerals.

Topics: Adult; Body Composition; Copper; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Thyroid Diseases; Zinc

To determine if serum leptin levels are affected by thyroid dysfunction, we measured its concentration in serum samples from 25 euthyroid controls and 25 subjects each with hypothyroidism and thyrotoxicosis collected over a 3-month period. Mean leptin levels in the euthyroid (24.1 +/- 8.3 microg/L), hypothyroid (22.7 +/- 7.0 microg/L) and thyrotoxic (23.3 +/- 4.3 microg/L) groups were not significantly different. Data were available to express leptin in terms of body mass index (BMI) in 11 euthyroid, and 6 untreated hypothyroid and thyrotoxic individuals. There was a significant positive correlation between BMI and leptin level (r = 0.60, p = .0002) for this subgroup, irrespective of their thyroid status. These data suggest that leptin levels are not affected by thyroid dysfunction.

Topics: Female; Humans; Hypothyroidism; Leptin; Male; Middle Aged; Proteins; Thyroid Diseases; Thyroid Function Tests; Thyrotoxicosis; Thyrotropin; Thyroxine

Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases maternal body fat and this additional energy is transferred to the offspring during lactation, since at weaning the dams had normal fat and the pups were obese. The higher fat and protein concentrations in the breast milk seemed to induce early overnutrition in the HF offspring. In addition to storing energy as fat, the HF offspring had a larger reserve of glycogen and hyperglycaemia that may have resulted from increased gluconeogenesis. Hyperleptinaemia may stimulate both adrenal medullary and thyroid

Topics: Adiponectin; Adiposity; Adrenal Gland Diseases; Animals; Diet, High-Fat; Epinephrine; Fatty Acids, Nonesterified; Female; Glucose; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Milk, Human; Norepinephrine; Obesity; Rats; Rats, Wistar; Thyroid Diseases; Thyroid Hormones; Weaning

Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.

Topics: Body Composition; Female; Humans; Leptin; Male; Thinness; Thyroid Diseases; Thyrotropin; Thyroxine

Topics: Animals; Humans; Leptin; Protein Binding; Rats; Thyroid Diseases

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.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Weight; Case-Control Studies; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Lipids; Middle Aged; Reference Values; Thyroid Diseases; Thyroid Hormones

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.

Topics: Adipose Tissue; Adult; Aged; Body Mass Index; Female; Humans; Leptin; Male; Middle Aged; Proteins; Sex Factors; Thyroid Diseases

To study interactions between leptin and the pituitary-thyroid axis, both in euthyroid and dysthyroid states.. We investigated the relationships of plasma leptin to levels of free thyroid hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30) and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were restudied during thyroxine replacement treatment.. Median [interquartile range] plasma leptin concentrations were highest in obese euthyroid subjects (31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels were higher in obese than in lean subjects (P < 0.00001). In obese subjects plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001) and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In untreated hyperthyroid, but not hypothyroid, patients plasma leptin concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of hypothyroidism with thyroxine resulted in a significant reduction in plasma leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P = 0.005), but BMI did not change significantly in the hypothyroid subjects being studied prospectively.. (i) In euthyroid subjects, plasma leptin and TSH levels correlate, and both are positively correlated with adiposity. (ii) Plasma leptin was significantly elevated in hypothyroid subjects, to levels similar to those seen in obese euthyroid subjects. (iii) Treatment of hypothyroidism resulted in a reduction in the raised plasma leptin levels. The data are consistent with the hypothesis that leptin and the pituitary-thyroid axis interact in the euthyroid state, and that hypothyroidism reversibly increases leptin concentrations.

Topics: Adult; Analysis of Variance; Body Mass Index; Female; Humans; Hyperthyroidism; Hypothyroidism; Leptin; Male; Middle Aged; Obesity; Pituitary Gland; Proteins; Thyroid Diseases; Thyroid Gland; Thyrotropin; Thyroxine; Triiodothyronine

Leptin is the protein product of the ob gene, secreted by adipocytes. It has been suggested that it may play an important role in regulating appetite and energy expenditure. The aim of this study was to evaluate a possible interaction of thyroid hormones with the leptin system. We studied 114 adult patients (65 females and 49 males): 36 were affected with primary hypothyroidism (PH), 38 with central hypothyroidism (CH) and 40 with thyrotoxicosis (TT). Patients with CH were studied both before and after 6 months of L-thyroxine replacement therapy. Body mass index (BMI; kg/m2), thyroid function and fasting serum leptin were assessed in all patients. Since BMI has been proved to be the major influencing variable of circulating leptin levels, data were expressed as standard deviation score (SDS) calculated from 393 male and 561 female controls matched for age and BMI. No difference in SDS was recorded between males and females whatever the levels of circulating thyroid hormones. In males, no significant difference was recorded among the SDSs of PH (-0.36 +/- 1.2), TT (-0.35 +/- 1.2) and CH (0.01 +/- 1.4) patients. Females with PH had an SDSs significantly lower than TT females (-0.77 +/- 1.0 vs -0.06 +/- 1.2; P < 0.02), while no significant differences between CH (-0.34 +/- 0.7) and TT females or between CH and PH females were observed. SDS in CH patients after 6 months of L-thyroxine therapy significantly varied only in females (0.25 +/- 1.4). In conclusion, circulating thyroid hormones do not appear to play any relevant role in leptin synthesis and secretion. However, as females with either overt hypo- or hyper-thyroidism or central hypothyroidism after L-thyroxine therapy show differences in their SDSs, a subtle interaction between sex steroids and thyroid status in modulating leptin secretion, at least in women, may occur.

Topics: Adult; Aged; Body Mass Index; Female; Humans; Hypothyroidism; Leptin; Male; Middle Aged; Proteins; Thyroid Diseases; Thyroid Hormones