NESS - Associations Between Leptin Signaling and Hyperparathyroidism

Associations Between Leptin Signaling and Hyperparathyroidism
*Gloria R. Sue¹, *Don Hoang¹, *Nathalie Abitbol¹, *Alexander Y. Li¹, *Nicole Pizzoferrato¹, Julie A. Sosa², Sanziana A. Roman², *Andrew T. DeWan¹, *Niclas Broer¹, *Xiaopan Yao¹, *Fangyong Li¹, *Ma-Li Wong³, *Julio Licinio³, *Christine Simpson¹, *Deepak Narayan¹
¹Yale University, New Haven, CT;²Duke University, Durham, NC;³Australian National University, Canberra, Australia

Objectives: The leptin signaling pathway plays a role in mediating obesity-related diseases. Obesity is associated with hyperparathyroidism. We sought to identify relationships between leptin signaling and hyperparathyroidism.
Design: Prospective cohort study
Setting: Academic hospital
Patients: Consecutive sample of 132 patients presenting for surgical treatment of hyperparathyroidism
Interventions: N/a
Main outcome measures: Serum leptin, parathyroid size, demonstration of leptin in parathyroids
Results: Both leptin and leptin receptor were detected within the chief cells of the parathyroid glands by in-situ hybridization, immunohistochemistry, and quantitative real-time polymerase chain reaction. Addition of leptin to parathyroid explant resulted in an increase in PTH secretion. Additionally, following surgery, leptin levels decreased significantly in patients with parathyroid adenoma (P<0.001) and parathyroid hyperplasia (P=0.002). On bivariate analysis, several factors were associated with changes in serum leptin levels, including gender, age, and BMI. 5 distinct single nucleotide polymorphisms (SNPs) in the leptin receptor (LEPR) gene were sequenced from blood samples from the patient cohort. One SNP, rs1137101, was associated with the size of the total parathyroid resected during surgery under a recessive model of inheritance (P=0.040). When only obese patients were analyzed, an additional SNP rs1137100 was significantly associated with the total parathyroid resected (P=0.034). No significant associations were observed among non-obese subjects.
Conclusions: Leptin appears to act on the parathyroids to stimulate PTH secretion as well as be secreted from parathyroid tissue. Additionally, our clinical data suggest that the parathyroid gland plays a role in regulating leptin production. Two SNPs in the leptin receptor gene are associated with increased parathyroid gland size, suggesting a potential genetic link for the clinical associations between hyperparathyroidism and obesity.

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