THE EFFECTS OF HUMAN GROWTH-HORMONE (GH) ADMINISTRATION IN GH-DEFICIENT ADULTS - A 20-DAY METABOLIC WARD STUDY

The early effects of human GH administration in GH-deficient (GHD) adu lts on protein, electrolyte homeostasis, and body composition were inv estigated in a metabolic ward study. Four patients were studied. In ad dition to a constant caloric and nitrogen (N)-sufficient diet, the pat ients received GH for 15 days in dosages of 12.5-25 mu g/kg.day, with a maximum of 1.48 mg (4 IU)/day. GH replacement therapy was well toler ated by all patients. There was a slowly increasing effect on IGF-I le vels, which reached a maximum after 8-12 days. The lowered IGFBP-3 lev els normalized quicker, reaching maximum circulating concentrations 3 days after the start of GH treatment. Insulin concentrations maximally increased after 5 days, after which they leveled off. Insulin-like gr owth factor-binding protein-1 levels were maximally suppressed after 2 days of treatment. N balance became positive in all patients (mean, 2.8 +/- 0.2 g/day). Maximal N retention occurred after 2-5 days of GH administration, after which adaptation occurred. This degree of N rete ntion represents a formation of 20 g muscle/day, which would mean an i ncrease of 3.6 kg muscle over a period of 6 months of GH replacement t herapy. A rapidly occurring positive sodium balance was observed withi n 24-72 h. Maximal sodium retention amounted to 61 mmol/day. It slowly decreased spontaneously over the subsequent 12 days. In parallel, rap id changes in bioelectrical impedance analysis (BIA) were observed. Th ere was a close parallel between the net cumulative sodium retention a nd the decrease in BIA in these patients during the first 15 days of G H therapy. This suggests that the calculation of body composition comp artments on the basis of BIA measurements during the initial phase of GH replacement does not represent actual changes in fat mass. This was substantiated with measurements of body composition using dual energy x-ray absorptiometry. In conclusion, measurements of early metabolic changes in GHD adults during the first 15 days after the start of GH r eplacement indicate that IGF-I values reach maximal levels only after 8-12 days, that the measurements of changes in IGFBP-1 and IGFBP-3 lev els probably do not contribute to a determination of the optimal GH re placement dose, that maximal N-retaining effects occur within 2-5 days , after which adaptation occurs, that massive sodium retention occurs during this period, which spontaneously levels off, and that cumulativ e sodium retention closely correlates during this period with changes in BIA. This suggests that measurements of body composition in patient s with GHD by BIA should be interpreted with caution.