2 WEEKS OF DAILY INJECTIONS AND CONTINUOUS-INFUSION OF RECOMBINANT HUMAN GROWTH-HORMONE (GH) IN GH-DEFICIENT ADULTS .1. EFFECTS ON INSULIN-LIKE GROWTH-FACTOR-I (IGF-I), GH AND IGF BINDING-PROTEINS, AND GLUCOSE-HOMEOSTASIS

Recombinant human growth hormone (GH) is routinely administered as dai ly subcutaneous injections to patients with GH deficiency (GHD). Howev er, in the hypophysectomized rat, pulsatile and continuous infusion of GH has been shown to differ in terms of the magnitude of effect on lo ngitudinal bone growth, serum insulin-like growth factor-I (IGF-I) con centrations, and hepatic metabolism. The aim of the present study was to compare the effects of daily injections and continuous infusion of GH in GHD adults on previously well documented GH dependent factors. R ecombinant human GH (0.25 U/kg/wk) was administered to nine men with G HD for 14 days in two different ways, ie, as a daily subcutaneous inje ction at 8 PM and as a continuous subcutaneous infusion, with 1 month of washout between treatments. Blood samples and tests were performed in the morning after an overnight fast before the start of GH treatmen t (day 0) and on day 2 and day 14 of treatment. An oral glucose tolera nce test (OGTT) was performed on day 0 and day 14. Daily injections an d continuous infusion of GH exerted similar effects in terms of body w eight and body composition. The two modes of administration resulted i n similar daily urinary GH excretion and similar serum GH concentratio ns in the morning. GH binding protein (GHBP) concentrations did not ch ange significantly during the various treatment periods. Serum IGF-I a nd IGF-I binding protein (IGFBP)-3 concentrations increased to a great er degree during continuous infusion of GH versus daily injections. Se rum IGFBP-I concentrations decreased to a similar degree during the tw o modes of administration. Serum concentrations of free triiodothyroni ne and total triiodothyronine (T-3) increased and free thyroxine (T-4) decreased to a similar degree, independent of the mode of administrat ion. However, total T-4 concentrations were unchanged during both mode s of treatment. Serum thyrotropin (TSH) concentrations decreased durin g continuous infusion, and there was a similar nonsignificant decrease during daily injections of GH. Fasting free fatty acid (FFA) levels i ncreased during treatment with one daily injection of GH, but there wa s no significant eff ect from continuous infusion. Results of measurem ents of fasting concentrations of blood glucose and oral glucose toler ance (OGT) indicated a more impaired glucose tolerance after daily inj ections of GH versus continuous infusion. In conclusion, continuous in fusion and daily injections of GH have similar effects on the variable s described, but the magnitude of the effects differs. Copyright (C) 1 996 by W.B. Saunders Company