Growth hormone replacement therapy improves body composition and increasesbone metabolism in elderly patients with pituitary disease

Although a specific GH deficiency (GHD) syndrome in the adult and the respo nse to GH replacement therapy are well recognized, there are few data avail able on the effect of GH replacement therapy in elderly GH-deficient patien ts. We studied the effect of GH therapy on body composition and bone minera l density measured by dual energy x-ray absorptiometry, markers for bone me tabolism, insulin-like growth factors (IGFs), and IGF-binding proteins (IGF BPs) in 31 patients (6 women and 25 men; aged 60-79 yr; mean, 68 yr) with m ultiple pituitary hormone deficiencies. The GH response to arginine or insu lin was below 3 mug/L (9 mU/L) in all subjects. They were randomized to GH (Humatrope, Eli Lilly & Co.) or placebo for 6 months, followed by 12 months of open treatment. The dose was 0.05 IU/kg.week for 1 month, and after tha t it was 0.1 IU/kg.week divided into daily sc injections (0.75-1.25 IU/day) . There were no changes in any of the measured variables during placebo treat ment. GH treatment normalized serum IGF-I in a majority of the patients and increased IGFBP-3 and -5 as well as IGFBP-4 and IGF-II to values within no rmal range. Lean body mass was increased, and the increase at 6 and 12 mont hs correlated with the increase in IGF-I (r = 0.46; P = 0.010 and r = 0.54, respectively; P = 0.003). GH treatment caused a modest, but highly signifi cant, reduction of total body fat. Mean bone mineral density was not differ ent from that in healthy subjects of the same age and did not change during the observation period. Markers for bone formation (bone-specific alkaline phosphatase activity, osteocalcin, and procollagen I carboxyl-terminal pep tide in serum) increased within the normal range, and levels were sustained throughout the study. The bone resorption marker (pyridinoline in urine) w as significantly elevated for 12 months. Side-effects were mild, mostly att ributed to fluid retention. In two patients with normal glucose tolerance a t the start of the study, pathological glucose tolerance occurred in one pa tient and was impaired in one. In conclusion, elderly patients with GHD respond to replacement therapy in a similar manner as younger subjects, with an improvement in body compositi on and an increase in markers for bone metabolism. Side-effects are few, an d elderly GHD patients can be offered treatment. As long-term risks are unk nown, GH doses should be titrated to keep IGF-I within the age-related phys iological range.