EFFECTS OF RECOMBINANT HUMAN GROWTH-HORMONE (GH) ON BONE AND INTERMEDIARY METABOLISM IN PATIENTS RECEIVING CHRONIC GLUCOCORTICOID TREATMENTWITH SUPPRESSED ENDOGENOUS GH RESPONSE TO GH-RELEASING HORMONE

Glucocorticoids, when administered over prolonged periods of time, cau se protein wasting, osteoporosis, elevation of total cholesterol, and carbohydrate intolerance. Human GH is a potent anabolic agent known to stimulate protein synthesis and osteoblast activity. Chronic hypercor tisolemia is associated with impaired GH secretion. The aim of our stu dy was to evaluate the effects of short term administration of human r ecombinant GH on bone and fuel metabolism in patients receiving chroni c glucocorticoid treatment and with suppressed GHRH-stimulated GH peak s (<10 mu g/L). We studied nine nonobese adult patients more than 70 y r of age (seven females and two males; age range, 41-68 yr; body mass index, 26 +/- 1.3 kg/m(2)) undergoing long term glucocorticoid therapy for nonendocrine diseases. After a 3-day stabilization period in the hospital, several parameters were evaluated in all patients: 1) protei n, 2) bone, 3) lipid, 4) carbohydrate metabolism, and 5) immune system function under baseline conditions. At 1800 h on the fifth day of hos pitalization, the patients began treatment with a daily sc injection o f 0.1 IU/kg (0.037 mg/kg) recombinant human GH (Humatrope, Eli Lilly C o.) for 7 days. GH administration caused a significant increase in nit rogen balance (from -0.12 +/- 0.04 to -0.03 +/- 0.02 g/kg.day; P < 0.0 5), osteocalcin, carboxy-terminal propeptide of type I procollagen, an d carboxyterminal telopeptide of type I collagen with respect to basal levels. After GH administration, total, high density lipoprotein, and low density lipoprotein cholesterol levels were significantly lowered , and serum triglyceride levels were increased in all patients. Normal blood glucose levels during GH administration were observed in our pa tients concomitantly with a slight increase in insulin secretion. Afte r GH treatment, the T-helper/T-suppressor cell ratio significantly inc reased with respect to basal levels (2.5 +/- 0.4 vs. 2.2 +/- 0.3; P < 0.05). Our data suggest that in patients receiving chronic glucocortic oid treatment, GH administration may significantly antagonize several side-effects of long term glucocorticoid administration, such as prote in wasting, osteoporosis, and hyperlipidemia.