Use of a GH receptor antagonist (GHRA) to explore the relationship between GH and IGF-I in adults with severe GH deficiency (GHD)

Objective : At diagnosis, approximately 50% of adults with severe GH deficiency (GHD) have an IGF-I within the reference range. It is unclear whether in such patients serum IGF-I levels are regulated by factors other than GH. Design and patients : We performed a double-blind, randomized, placebo-controlled, cross-over study to investigate the effect of the GH receptor antagonist - pegvisomant (20 mg daily for 14 days) on GH and IGF-I levels in three cohorts: patients with GHD and a normal IGF-I (NORMS); patients with GHD and a low IGF-I (LOWS) and healthy volunteers (CONS). Results : Pegvisomant decreased IGF-I in CONS and NORMS [158·5 (101-206) vs. 103 (77-125) μg/l, P <0·01; 124 (81-136) vs. 95 (51-113) μg/l, P <0·01 respectively], but not in LOWS [31 (<31-32) vs. 34·5 (<31-38) μg/l], and this was associated with an increase in mean 24 h GH in CONS [0·49 (0·12-0·89) to 1·38 (0·22-2·45) μg/l (P = 0·03)] and in NORMS [69 (0-320)% from 0·1 (<0·1-0·13) to 0·17 (0·11-0·42) μg/l (P = 0·03)], but not in the LOWS. The peak GH response to arginine was increased by pegvisomant in CONS and NORMS [6·1 (0·8-9) vs. 20·4 (13·1-28·8) μg/l, P = 0·03; 0·4 (0·1-0·5) vs. 0·5 (0·3-0·6) μg/l, respectively], but not in LOWS. Conclusions : These data indicate that patients with severe GHD with a normal IGF-I are able to increase GH secretion in response to a pegvisomant-induced fall in IGF-I, whereas those with low IGF-I levels are unable to increase GH secretion. Therefore circulating IGF-I appears to be GH-independent in GHD patients with a low IGF-I, but remains partially GH-dependant in GHD patients with a normal IGF-I. © 2009 Blackwell Publishing Ltd.