Elevated leptin concentrations in growth hormone-deficient hypopituitary adults

Abstract

Background: Hypopituitarism with growth hormone (GH) deficiency is associated with obesity characterized by central (abdominal) distribution of fat. Recent work has demonstrated that leptin, a product of obese gene, is raised in obesity.

Objective: To study circulating leptin levels in GH-deficient hypopituitary adults and to investigate its anthropometric, gender and metabolic relations.

Methods: After an overnight fast of 10-12 hours, anthropometric parameters and body composition were measured and blood was collected for the measurement of circulating leptin, glucose, intact insulin, proinsulin, IGF-I, total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol.

Subjects: Fifteen (7 men) GH-deficient hypopituitary adults (maximum stimulated serum GH to provocative testing < 6 mU/l) and 21 (10 men) normal control subjects matched for age, gender and body mass index (BMI).

Results: Fasting serum leptin was significantly higher in hypopituitary patients than controls (12.0 +/- 1.8 vs 8.0 +/- 1.5 micrograms/l, P = 0.04). The increase was more marked in obese (BMI > 26.0 kg/m2) patients compared with obese controls (15.3 +/- 2.0 vs 8.8 +/- 2.3 micrograms/l, P = 0.03) than in lean patients and controls. Obese control women and men had higher leptin levels than non-obese (women, 16.6 +/- 2.7 vs 8.6 +/- 0.6 micrograms/l, P = 0.03; men, 4.9 +/- 0.5 vs 2.9 +/- 0.6 micrograms/l, P = 0.035). Similar changes were observed for obese versus non-obese patients, although the changes did not reach statistical significance. Women in each group had significantly higher leptin concentrations than men (patients: 15.5 +/- 2.3 vs 7.3 +/- 1.4 micrograms/l, P = 0.009; controls: 12.6 +/- 2.4 vs 4.3 +/- 0.5 micrograms/l, P = 0.0001). These gender differences remained significant even when expressed in relation to BMI (patients: 0.57 +/- 0.09 vs 0.26 +/- 0.05 ng.m2/ml.kg, P = 0.009; controls: 0.43 +/- 0.05 vs 0.16 +/- 0.02 ng.m2/ml.kg, P = 0.0001). Serum leptin was positively associated with body mass index (P = 0.003), percentage body fat mass (P = 0.0001) and inversely related with age (P = 0.043). It demonstrated no relation with body weight, waist circumference, waist to hip ratio, fasting IGF-I, glucose, insulin, proinsulin, total cholesterol, triglycerides, HDL and LDL cholesterol in patients nor controls; 85% of variance in leptin was explained by a model including body mass index, gender, age and hypopituitarism.

Conclusions: Leptin concentrations are raised in GH-deficient hypopituitary adults to a greater extent than would be expected from the degree of obesity.