Thorén MC, Wivall-Helleryd I-L. Blum WF, Hall KE. Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency. Eur J Endocrinol 1994;131:33–40. ISSN 0804–4643
Insulin-like growth factor I (IGF-I) circulates bound to specific binding proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We administered recombinant IGF-I (40 μg/kg body wt, from Kabi Pharmacia) in a morning dose (08.00 h) for seven consecutive days to six patients (21–47 years) with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood sampling was performed on days 1 and 7, otherwise morning samples were drawn. The mean serum total IGF-I was maximal 3–4 h after the injection. A higher peak and basal value (p < 0.05) was observed on day 7 when compared to that observed on day 1. The concentrations were 237 vs 190 μg/l and 43 vs 22 μg/l. The mean free IGF-I increased concomitantly to 17 and 20 μg/l after 2–3 h on days 1 and 7. After 4 h, IGF-II was decreased (p <0.05) from 340 to 291 μg/l on day 1 and from 341 to 252 μg/l on day 7. The IGF-I area under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the patient with the highest IGFBP-3 level obtained IGF-I levels above 100 μg/l for 24 h. In spite of unchanged glucose levels, there was a modest suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were fasting. A small decline of mean potassium concentrations was found 2–6 h after the injection on day 1. During a week with daily injections, the morning serum IGF-I increased slightly in comparison to basal levels but no significant change in morning values of IGFBP-1, -2, -3, glucose and insulin were observed. Serum urea, creatinine, cholesterol and free fatty acid decreased significantly, indicating metabolic effects of IGF-I. Thus IGF-I has metabolic effects in doses not leading to hypoglycemia. To achieve a normal diurnal IGF-I level, recombinant IGF-I should be administered two or three times per 24 h in subjects with subnormal IGFBP-3 levels.
Marja Thorén, Department of Endocrinology and Diabetology, Karolinska Hospital, S-171 76 Stockholm, Sweden