Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency.
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 micrograms/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 micrograms/l and 43 vs 22 micrograms/l. The mean free IGF-I increased concomitantly to 17 and 20 micrograms/l after 2-3 h on days 1 and 7. After 4 h, IGF-II was decreased (p < 0.05) from 340 to 291 micrograms/l on day 1 and from 341 to 252 micrograms/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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Thorén
M C
MC
Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden.
Wivall-Helleryd
I L
IL
Blum
W F
WF
Hall
K E
KE
D000328:Adult; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013006:Growth Hormone / Q000172:deficiency*; D006801:Humans; D007018:Hypopituitarism / Q000150:complications; D007279:Injections, Subcutaneous; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone