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Impact of Growth Hormone and Dehydroepiandrosterone on Protein Metabolism in Glucocorticoid-Treated Patients

Garvan Institute of Medical Research (M.G.B., G.J., D.J.C., K.K.Y.H.), Sydney, New South Wales 2010, Australia; Department of Endocrinology (M.G.B., D.J.C., K.K.Y.H.), St. Vincent’s Hospital, Sydney, New South Wales 2010, Australia; University of New South Wales (M.G.B., D.J.C., K.K.Y.H.), Sydney, New South Wales 2052, Australia; and Department of Diabetes and Endocrinology, Guy’s, King’s and St. Thomas’ School of Medicine, St. Thomas’ Hospital (A.M.U.), London SE1 7EH, United Kingdom

Address all correspondence and requests for reprints to: Professor Ken K. Y. Ho, Pituitary Research Unit, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail: k.ho{at}garvan.unsw.edu.au.

Context: Chronic pharmacological glucocorticoid (GC) use causes substantial morbidity from protein wasting. GH and androgens are anabolic agents that may potentially reverse GC-induced protein loss.

Objective: Our objective was to assess the effect of GH and dehydroepiandrosterone (DHEA) on protein metabolism in subjects on long-term GC therapy.

Design: This was an open, stepwise GH dose-finding study (study 1), followed by a randomized cross-over intervention study (study 2).

Setting: The studies were performed at a clinical research facility.

Patients and Intervention: In study 1, six subjects (age 69 ± 4 yr) treated with long-term (>6 months) GCs (prednisone dose 8.3 ± 0.8 mg/d) were studied before and after two sequential GH doses (0.8 and 1.6 mg/d) for 2 wk each. In study 2, 10 women (age 71 ± 3 yr) treated with long-term GCs (prednisone dose 5.4 ± 0.5 mg/d) were studied at baseline and after 2-wk treatment with GH 0.8 mg/d, DHEA 50 mg/d, or GH and DHEA (combination treatment).

Main Outcome Measure: Changes in whole body protein metabolism were assessed using a 3-h primed constant infusion of 1-[¹³C]leucine, from which rates of leucine appearance, leucine oxidation, and leucine incorporation into protein were estimated.

Results: In study 1, GH 0.8 and 1.6 mg/d significantly reduced leucine oxidation by 19% (P = 0.03) and 31% (P = 0.02), and increased leucine incorporation into protein by 10% (P = 0.13) and 19% (P = 0.04), respectively. The lower GH dose did not cause hyperglycemia, whereas GH 1.6 mg/d resulted in fasting hyperglycemia in two of six subjects. In study 2, DHEA did not significantly change leucine metabolism alone or when combined with GH. Blood glucose was not affected by DHEA.

Conclusion: GH, at a modest supraphysiological dose of 0.8 mg/d, induces protein anabolism in chronic GC users without causing diabetes. DHEA 50 mg/d does not enhance the effect of GH. GH may safely prevent or reverse protein loss induced by chronic GC therapy.