REPLACEMENT TREATMENT WITH BIOSYNTHETIC HUMAN GROWTH-HORMONE IN GROWTH HORMONE-DEFICIENT HYPOPITUITARY ADULTS

OBJECTIVES The physiological role of growth hormone in adult life has recently attracted increased interest. We have studied the clinical ef fects and the effects on body composition of prolonged replacement wit h biosynthetic human CH in,a large number of hypopituitary adults. DES lGN A randomized double blind placebo controlled trial for 6 months-fo llowed by an open trial of GH treatment for 12 months. GH daily dose w as 0.04 (0.02-0.05) IU/ kg s.c. PATIENTS Forty GH deficient hypopituit ary patients (19 M, 21 F; aged 19-67 years) on conventional replacemen t therapy were studied. MEASUREMENTS Serum insulin-like growth factor I(IGF-I), skinfold thickness, total body potassium, total body water ( TBW), exercise tolerance and muscle strength, and well-being. RESULTS During the 6-month double blind phase, two GH treated patients withdre w because of adverse events. Lean body mass (LBM) increased and percen tage body fat (%BF) decreased on GH but not on placebo (PF (LBM: (GH: from 48.5 +/- 9.6 to 49.6 +/- 9.5 kg; P: from 50.7 +/- 9.2 to 50.1 +/- 9.0 kg, P < 0.05 GH vs P) and %BF (GH: from 34.7 +/- 11.4 to 34.2 +/- 10.7; P: from 37.4 +/- 7.6 to 38.7 +/- 8.1, P < 0.05 GH vs P)). TBW i ncreased on GH (P < 0.01) but not on P. No change was observed in wais t-to-hip ratio or in muscle strength. During longer-term follow-up com bining the double blind and open phase components of the study, 34, 27 and 11 patients received GH for 6, 12 and 18 months respectively. Pat ients dropped out because of adverse events or lack of perceived benef it. Skinfold thicknesses decreased significantly at 6 and 12 months an d the waist circumference at 6 months. Waist-to-hip ratio decreased si gnificantly on GH at 12 months. LBM increased on GH treatment from 49. 6 +/- 9.1 to 51.6 +/- 9.4 kg (P < 0.0006), 51.9 +/- 8.9 kg (P < 0.07) and 53.1 +/- 10.5 kg (P < 0.0001) at 6, 12 and 18 months respectively. Percentage body fat decreased on GH from 37.2 +/- 10.7 to 34.7 +/- 10 .1 (P < 0.005), 35.1 +/- 12.8 (NS) and 34.5 +/- 8.6 (P < 0.04) at 6, 1 2 and 18 months respectively. TBW also increased at 6 and 12 months of GH treatment. Exercise time increased significantly at 6, 12 and 18 m onths of GH treatment. Muscle strength in selected: muscle, groups inc reased significantly at 6, 12 or 18 months of GH treatment. Randomizat ion resulted in the placebo group having a greater GHQ score, (higher morbidity) than the GH group before therapy. Over the controlled phase , GHQ scores improved:on placebo but not on GH and CPRS score was unch anged in either group. In the open phase, the GHQ score did not change on GH therapy but CPRS score improved at 6 and 12 months. CONCLUSIONS Growth hormone replacement therapy in adults for 6 months increased l ean body mass, total body water and exercise tolerance, and decreased body fat. Growth hormone replacement for longer than 6 months maintain s the advantageous effects seen in shorter-term studies and may have a dditional effects on body fat distribution, muscle strength and psycho logical wellbeing.