leptin and Hyperparathyroidism

Vitamin D deficiency and adipocytokines have been implicated in the etiology of aging-related diseases such as cancer, osteoporosis, and diseases of the cardiovascular system. The association between elevated parathyroid hormone (PTH) and low 25-hydroxyvitamin D (25-OH-VitD) in plasma is used to define vitamin D deficiency, yet their associated mechanistic pathways are unclear. Utilizing plasma samples from women in a previous intervention study, we measured plasma 25-OH-VitD, leptin, adiponectin, PTH, and lipid levels. We observed strong positive associations for leptin with PTH, gamma -tocopherol, and body mass index (BMI) and inverse associations with 25-OH-VitD and adiponectin. Although commonly accepted that vitamin D deficiency causes hyperparathyroidism, we observed this association primarily in individuals with elevated leptin levels, suggesting that leptin may be an important modifier of this effect consistent with 25-OH-VitD-mediated inhibition of leptin. Leptin was highly correlated with the BMI/25-OH-VitD ratio (r = 0.80; P < 0.0001), consistent with a model in which BMI (adiposity) and 25-OH-VitD are the primary determinants of circulating leptin and PTH levels. This model may explain the failure of some studies to observe elevated PTH in vitamin D deficient adolescents and provides important insight into epidemiological studies exploring the associations of these individual biomarkers with chronic disease risk and mortality.

Topics: Adiponectin; Adult; Body Mass Index; Carotenoids; Diet; Female; Fruit; Humans; Hyperparathyroidism; Leptin; Lipids; Parathyroid Hormone; Regression Analysis; Risk Factors; Vegetables; Vitamin D; Vitamin D Deficiency

We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms.. The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones.. From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays.. Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline.. Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

Topics: Adenoma; Animals; Cells, Cultured; Humans; Hyperparathyroidism; Hyperplasia; Immunohistochemistry; Leptin; Mice, Knockout; Microscopy, Confocal; Microscopy, Fluorescence; Microscopy, Immunoelectron; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Prospective Studies; Receptors, Leptin; RNA, Messenger

The role of leptin in mediating calcium-related metabolic processes is not well understood.. We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism.. Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively).. Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.

Topics: Adult; Aged; Aged, 80 and over; Female; Genotype; Humans; Hyperparathyroidism; Leptin; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroidectomy; Polymorphism, Single Nucleotide; Prospective Studies; Receptors, Leptin; Signal Transduction; Young Adult

Topics: Female; Humans; Hyperparathyroidism; Leptin; Male; Polymorphism, Single Nucleotide; Receptors, Leptin; Signal Transduction

Primary hyperparathyroidism (PHPT) is considered a state of insulin resistance. However, it is unclear whether the state of insulin resistance and adverse levels of adipocytokines are reversed in PHPT patients who have undergone curative parathyroidectomy.. Ten consecutive patients with PHPT were studied at baseline and three months after curative parathyroid surgery in this prospective interventional study. Fasting blood calcium, intact parathyroid hormone (PTH), glucose, insulin, adiponectin and leptin concentrations were measured. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA- IR) and insulin sensitivity, by the quantitative insulin sensitivity check index (QUICKI).. Four out of the ten patients were male. The mean age of the patients was 32.40 +/- 11.42 years, and the mean body mass index was 23.70 +/- 5.19 kg/m2. The HOMA-IR value was found to be higher, while the QUICKI value was significantly lower before surgery in patients with PHPT compared to the published reference ranges. Serum leptin concentrations were higher in patients with PHPT than in normal healthy individuals; however, there was no difference in the adiponectin concentrations. There was no statistical difference in the mean values of fasting plasma glucose, plasma insulin, leptin, adiponectin, as well as the HOMA-IR and QUICKI estimates three months postoperatively, as compared to the preoperative measures.. Peripheral insulin resistance/sensitivity and the concentrations of leptin and adiponectin did not change three months after curative parathyroidectomy.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Body Mass Index; Calcium; Female; Glucose; Humans; Hyperparathyroidism; Insulin; Insulin Resistance; Leptin; Male; Parathyroid Hormone; Parathyroidectomy

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.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; Blood Pressure; Body Mass Index; Calcium; Cardiovascular Diseases; Cholesterol; Female; Heart Rate; Humans; Hyperparathyroidism; Leptin; Magnesium; Male; Metabolic Syndrome; Middle Aged; Parathyroid Hormone; Phosphorus; Uric Acid