Continuation of growth hormone (GH) replacement in GH-Deficient patients during transition from childhood to adulthood: A two-year placebo-controlledstudy

Previous studies have demonstrated beneficial effects of GH replacement, in adults with GH deficiency (GHD), on body composition, physical fitness, an d quality of life. These studies, however, concern patients with adult-onse t GHD or childhood-onset (CO) patients enrolled several years after withdra wal of initial therapy. So far, the effects of continuation of GH-administr ation in patients with CO-GHD have not been examined. We studied a group of nineteen young adults (13 males + 6 females; 16-26 yr old; mean age, 20.2 +/- 0.65 yr) with CO-GHD, in a randomized, parallel, double-blind, placebo- controlled trial for 1 yr, followed by an open phase with GH for 1 yr. All patients received GH therapy at the start of study, and trial medication (G H/placebo) was given in a similar dose. Patients randomized to continued GH treatment exhibited no significant changes in any parameters tested, but i ntra- and interindividual variations in insulin-like growth factor (IGF)-I levels could suggest compliance problems. Discontinuation of GH for 1 yr re sulted in a decrease in serum IGF-I, from 422.0 +/- 56.8 to 147.8 +/- 33.4 mu g/L, in the placebo group (P = 0.003). After discontinuation of GH for 1 yr, an increase in total body fat (TBF, kg), measured by dual-energy x-ray absorptiometry scan, was seen [placebo: 22.7 +/- 2.7 to 26.5 +/- 2.5 (P = 0.01); GH:16.2 +/- 2.1 to 17.2 +/- 2.1 (not significant)]. Resumption of GH after placebo was followed by increments in serum IGF-I(mu g/L) [from 147. 8 +/- 33.4 to 452 +/- 76 (P = 0.001)] and IGF-binding protein 3, as well as in fasting glucose (mmol/L) [4.9 +/- 0.2 vs. 5.3 +/- 0.2 (P = 0.03)]. Afte r resumption of GH lean body mass (kg) increased [52.4 +/- 4.9 vs. 60.7 +/- 5.6 (P = 0.006)]. Likewise, resumption of GH therapy increased thigh muscl e volume and thigh muscle/fat ratio, as assessed by computed tomography [mu scle volume (cm(2)/10 mm): 118.2 +/- 11.7 vs. 130.0 +/- 10.9 (P = 0.002); m uscle/fat ratio: 1.33 +/- 0.24 us. 1.69 +/- 0.36 (P = 0.02)]. In conclusion, discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant and potentially unfavorable changes in IGF-I and body composition, both of which are rever sed after resumption of GH treatment. By contrast, continuation of GH thera py results in unaltered IGF-I and body composition. We recommend continuati on of GH therapy in these patients, to be undertaken in collaboration betwe en pediatricians and adult endocrinologists.