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Wednesday 09 January 2008

Impact of growth hormone and dehydroepiandrosterone on protein metabolism in glucocorticoid-treated patients.

By: Burt MG, Johannsson G, Umpleby AM, Chisholm DJ, Ho KK.

J Clin Endocrinol Metab 2008 Jan;(): [Epub ahead of print]

Context: Chronic pharmacological glucocorticoid (GC) use causes substantial morbidity from protein wasting. Growth hormone (GH) and androgens are anabolic agents that may potentially reverse GC-induced protein loss. Objective: To assess the effect of GH and dehydroepiandrosterone (DHEA) on protein metabolism in subjects on long-term GC therapy. Design: An open, stepwise GH dose-finding study (Study 1) followed by a randomized crossover intervention study (Study 2). Setting: A clinical research facility. Patients and intervention: In Study 1, 6 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 (0.8mg/d and 1.6mg/d) for two weeks 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 two weeks 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-[(13)C] leucine, from which rates of leucine appearance (leucine Ra), leucine oxidation (Lox) and leucine incorporation into protein (LIP) were estimated. Results: In Study 1, GH 0.8 mg/d and 1.6 mg/d significantly reduced Lox by 19% (p=0.03) and 31% (p=0.02) and increased LIP by 10% (p=0.13) and 19% (p=0.04) respectively. The lower GH dose did not cause hyperglycaemia, whereas GH 1.6 mg/d resulted in fasting hyperglycemia in two of 6 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 supraphysiologic 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.

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