Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study.
Previous studies have demonstrated beneficial effects of GH replacement, in adults with GH deficiency (GHD), on body composition, physical fitness, and quality of life. These studies, however, concern patients with adult-onset GHD or childhood-onset (CO) patients enrolled several years after withdrawal of initial therapy. So far, the effects of continuation of GH-administration 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 (GH/placebo) was given in a similar dose. Patients randomized to continued GH treatment exhibited no significant changes in any parameters tested, but intra- and interindividual variations in insulin-like growth factor (IGF)-I levels could suggest compliance problems. Discontinuation of GH for 1 yr resulted in a decrease in serum IGF-I, from 422.0 +/- 56.8 to 147.8 +/- 33.4 microg/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 (microg/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)]. After 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 muscle volume and thigh muscle/fat ratio, as assessed by computed tomography [muscle volume (cm2/10 mm): 118.2 +/- 11.7 vs. 130.0 +/- 10.9 (P = 0.002); muscle/fat ratio: 1.33 +/- 0.24 vs. 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 reversed after resumption of GH treatment. By contrast, continuation of GH therapy results in unaltered IGF-I and body composition. We recommend continuation of GH therapy in these patients, to be undertaken in collaboration between pediatricians and adult endocrinologists.
Vahl
N
N
Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Denmark. nvahl@dadlnet.dk
Juul
A
A
Jørgensen
J O
JO
Orskov
H
H
Skakkebaek
N E
NE
Christiansen
J S
JS
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D001835:Body Weight; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000503:physiopathology; D010809:Physical Fitness; D010919:Placebos; D011788:Quality of Life; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D019382:Human Growth Hormone; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D008074:Lipoproteins; D010919:Placebos; D014280:Triglycerides