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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 1 107-116
Copyright © 1998 by The Endocrine Society

Original Studies

The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults1

Ross C. Cuneo, Steve Judd, Jennifer D. Wallace, Don Perry-Keene, Henry Burger2, Sylvia Lim-Tio, Boyd Strauss, Jan Stockigt, Duncan Topliss, Frank Alford, L. Hew, Hans Bode, Ann Conway, David Handelsman, Stewart Dunn, Steve Boyages, N. Wah Cheung and David Hurley

Endocrine Unit, Flinders Medical Centre (S.J.), Adelaide; Metabolic Research Unit, University of Queensland, Princess Alexandra Hospital (R.C.C., J.D.W.) Brisbane; Endocrine Unit, Royal Brisbane Hospital (D.P-K.), Brisbane; Prince Henry’s Institute of Medical Research, and Body Composition Laboratory, Monash Medical Centre (H.B., S.L-T., B.S.), Melbourne; Ewen Downie Metabolic Unit, Alfred Hospital (J.S., D.T.), Melbourne; Endocrine Unit, St. Vincent’s Hospital (F.A., L.H.), Melbourne; Paediatric Endocrine Unit, Sydney Children’s Hospital (H.B.), Sydney; Andrology Unit, Royal Prince Alfred Hospital (A.C., D.H.), Sydney; Medical Psychology Unit, University of Sydney (S.D.), Sydney; Endocrine Unit, Westmead Hospital (S.B., N.W.C.), Sydney; and Department of Diabetes and Endocrinology, Royal Perth Hospital (D.H.), Perth, Australia

Address all correspondence and requests for reprints to: Ross C. Cuneo, University Department of Medicine, Princess Alexandra Hospital, Wooloongabba, Brisbane, 4102, Australia. E-mail: cuneo2{at}gpo.pa.uq.edu.au

GH treatment in adults with GH deficiency has numerous beneficial effects, but most studies have been small. We report the results of an Australian multicenter, randomized, double-blind, placebo-controlled 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. Patients 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 ± 1 yr (±SEM; range 17–67 yr) were recruited. Serum insulin-like growth factor-I (IGF-I) increased from a standard deviation score of -2.64 ± 0.27 (range -8.8 to +3.82; n = 78) to +1.08 ± 2.87 (range -7.21 to +6.42) 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 (±2 SD) pretreatment levels, respectively]. Fasting total cholesterol (P = 0.042) and low-density lipoprotein cholesterol (P = 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 = 0.002). Fat mass measured by DEXA (P < 0.001), skinfold thicknesses (P < 0.001), and waist/hip ratio (P = 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 reaction 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 = 0.016). Such symptoms were mild and resolved in 70% of patients despite continued treatment. 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-density 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.




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