Effects of recombinant human growth hormone on basal metabolic rate in adults with pituitary deficiency

Abstract

The effect of recombinant human growth hormone (rhGH) on basal metabolic rate (BMR) was studied in a placebo-controlled, double-blind, crossover trial. Ten patients with a history of complete pituitary insufficiency were randomized for 26 weeks in each period. Three patients were excluded due to withdrawal, fever, and claustrophobia, respectively. All patients had received adrenal, thyroid, and gonadal substitution therapy for at least 1 year before the study. The dose of rhGH was 0.25 to 0.5 U/kg/wk, administered subcutaneously once a day in the evening. BMR was determined by indirect calorimetry in a computerized ventilated open-hood system. Body composition was examined using four different methods—computed tomography (CT), tritium dilution, 40K determinations, and total body nitrogen (TBN) measured with neutron activation. The body composition data have previously been reported. Fat-free mass (FFM) increased and body fat (BF) decreased during the first 6 weeks of rhGH treatment, but no further changes in body composition occurred between 6 and 26 weeks. Baseline BMRs in GH-deficient (GHD) patients were in the lower part of the reference range, but BMR and the ratio between BMR and FFM (BMR/FFM) were not significantly lower than in a carefully selected control group. BMR increased between 0 and 6 weeks (mean ± SD: from 6.68 ± 1.55 to 7.75 ± 1.35 MJ/24 h, P < .001) and then remained unchanged between 6 and 26 weeks. The increase in BMR was closely related to the increase in FFM ( r = .91, P < .01). However, the increase in BMR was not solely related to changes in FFM, since there was a significant increase in BMR/FFM at 6 weeks that was maintained at 26 weeks. Pearson correlation analysis also revealed a close association between the increase in BMR after 6 weeks of rhGH treatment and increases in a number of metabolic variables, including total 3,5,3′-triiodothyronine ([T 3] r = .84, P < 0.05), procollagen III peptide ([pIIIp] r = .85, P < .05), and free fatty acids ([FFA] r = .95, P < .01). Therefore, the increase in BMR after rhGH treatment is not simply a reflection of altered body composition, but may also involve other mechanisms including lipolysis, increased thyroxine (T 4) deiodination resulting in increased circulating T 3 concentrations, and/or increased protein synthesis as demonstrated by increased circulating pIIIp levels.