Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

Abstract

OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH deficiency. DESIGN: Stimulation with GHRH. (1 μg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH+ARG was evaluated in a second session. SUBJECTS: Forty-five patients with simple obesity (OB 11 male and 34 female, age 40.5±1.8 y, BMI 38.8±1.1 kg/m²), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6±2.4 y, 24.7±0.7 kg/m²) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8±1.0 y, 21.6±0.3 kg/m²) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at −60 and 0 min, and than every 15 min up to +120 min. Basal IGF–I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF–I levels in OB were lower (P<0.005) than those in NS but higher (P<0.005) than those in GHD. Mean peak GH response to GHRH+ARG in OB was clearly lower than that in NS (P<0.005) and higher (P<0.005) than that in GHD. Sixty–percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 μg/l) while 4% OB and only 53% GHD with GH responses lower than 3 μg/l, the limit under which GH replacement therapy of severe deficiency is allowed. Good intraindividual reproducibility of the GH response to GHRH+arginine test was present in all groups (OB: r=0.78, P<0.0001; GHD: r=0.57, P<0.003; NS: r=0.74, P<0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH deficiency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH+arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH deficiency.