The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults

Publisher Website
Google Scholar
Abstract
GH treatment in adults with GH deficiency has numerous bene- ficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-con- trolled trial of the effects of recombinant human GH treatment in adults with GH deficiency. GH deficiency was defined as a peak serum GH of ,5 mU/liter in response to insulin-induced hypoglycemia. Pa- tients were randomly assigned to receive either GH (0.125 U/kg per week for 1 month and 0.25 U/kg per week for 5 months) or placebo. After 6 months, all patients received GH. The primary end points were biochemical responses, body composition, quality of life, and safety. One hundred sixty-six patients (72 females and 91 males) with a mean age of 40 6 1y r ( 6SEM; range 17- 67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard devi- ation score of 22.64 6 0.27 (range 28.8 to 13.82; n 5 78) to 11.08 6 2.87 (range 27.21 to 16.42) at 6 months in the GH/GH group; 38% of the whole group were above the age-specific reference range following treatment (17.6% and 68.9% with subnormal (,2 SD) or normal (62 SD) pretreatment levels, respectively). Fasting total cholesterol (P 5 0.042) and low-density lipoprotein cholesterol (P 5 0.006) decreased over the first 6 months. Fat-free mass increased in the first 6 months whether measured by bioelectrical impedance (P , 0.001) or dual energy x-ray absorptiometry (DEXA; P , 0.001). Total-body water increased in the first 6 months whether measured by bioelectrical impedance (P , 0.001) or deuterium dilution (P 5 0.002). Fat mass measured by DEXA (P , 0.001), skinfold thicknesses (P , 0.001), and waist/hip ratio (P 5 0.001) decreased in the first 6 months. Most changes in body composition were complete by 3 months of treatment and maintained to 12 months. Whole-body bone mineral density (BMD) (by DEXA) was unaffected by GH treatment. Self-reported quality of life was considered good before treatment, and beneficial treatment effects were observed for energy, pain, and emotional re- action as assessed by the Nottingham Health Profile. In the initial 6 months, adverse effects were reported by 84% of patients in the GH and 75% in the placebo group, with more symptoms relating to fluid retention in the GH group (48% vs. 30%; P 5 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treat- ment. Resting blood pressure did not change over the initial 6 months. In summary, GH treatment in adults with GH deficiency resulted in 1) prominent increases in serum IGF-I at the doses employed, in some cases to supraphysiological levels; 2) modest decreases in total- and low-den- sity lipoprotein cholesterol, together with substantial reductions in total- body and truncal fat mass consistent with an improved cardiovascular risk profile; 3) substantial increases in lean tissue mass; and 4) modest improvements in perceived quality of life. The excessive IGF-I response and side-effect profile suggest that lower doses of GH may be required for prolonged GH treatment in adults with severe GH deficiency. (J Clin Endocrinol Metab 83: 107-116, 1998)

This publication has 0 references indexed in Scilit: