CONTINUOUS-INFUSION VERSUS DAILY INJECTIONS OF GROWTH-HORMONE (GH) FOR 4 WEEKS IN GH-DEFICIENT PATIENTS

Endogenous GH secretion is pulsatile. Animal studies indicate that GH administered in a pulsatile manner induces growth and insulinlike grow th factor I (IGF-I) generation more effectively than continuous admini stration. Short term human studies, however, have reported similar met abolic effects with constant and pulsatile GH delivery. This study was carried out to compare the metabolic effects of longer term continuou s infusion vs. daily injections of GH. Thirteen GH-deficient patients were studied in a cross-over design. The patients were randomized to r eceive GH as a continuous sc infusion by means of a portable pump for 1 month and as daily sc injections (at 1900 h) for another month. An a verage daily GH dosage (+/-SEM) of 3.15 +/- 0.27 IU was administered d uring both periods. Steady state 24-h profiles of GH, IGF-I, IGF-bindi ng proteins (IGFBPs), insulin, glucose, lipid intermediates, and other metabolites were monitored after each treatment period. At the end of each study period (at 0800 h), an oral glucose tolerance test was per formed. The mean (+/-SEM) integrated levels of serum GH (micrograms pe r L) were higher after GH injection [2.51 +/- 0.54 (injection) us. 1.7 7 +/- 0.35 (infusion); P < 0.02]. Continuous infusion induced higher n ighttime than daytime GH levels (P = 0.01), indicating a diurnal varia tion in the absorption or clearance of GH. Serum IGF-I levels (microgr ams per L were slightly higher (P < 0.05, by analysis of variance) alt er continuous GH infusion [312.5 +/- 50.2 (injection and 334.6 +/- 46. 6 (infusion)]. Similarly, constant GH delivery induced higher IGFBP-3 levels (P < 0.05, by analysis of variance). Serum IGFBP-1 levels were similar on the two occasions. Daily GH injections increased daytime in sulin levels (P < 0.05), whereas 24-h levels were similar (P = 0.14). The trend toward increased insulin levels after GH injections was also found during the oral glucose tolerance test (P = 0.07). Blood glucos e levels were identical on the two occasions. Nocturnal levels of none sterified fatty acids were higher (P < 0.05) after GH injection. We co nclude that continuous sc infusion of GH induced serum IGF-I and IGFBP -3 levels more effectively than daily sc injections. The constant appe arance of GH in the circulation did not impair glucose tolerance, but resulted in a less physiological diurnal pattern of nonesterified fatt y acids. Our data do not support the concept that a pulsatile GH patte rn is of critical physiological significance.