Insulin-like growth factor-I and IGF binding protein-3 remain high after GnRH analogue therapy in girls with central precocious puberty

Objective. IGF-I rises in normal adolescence and in central precocious puberty (CPP), secondary to a rise in sex steroids and GH. The aim of this study was to examine changes in serum IGF-I and its major binding protein IGFBP-3 after pharmacological arrest of puberty. Patients and Measurements. Ten girls diagnosed for CPP were evaluated before and during the first 3 months of GnRH analogue (GnRHa) therapy aimed at suppression of the gonadal axis. Serum IGF-I was measured by immunoradiometric assay (IRMA) and IGFBP-3 by both IRMA and Western ligand blotting (WLB). Results. Serum IGF-I was markedly higher in patients with CPP as compared with age matched controls (48.8 ± 6.5 vs 23.1 ± 4.9 nmol/l, P < 0.01). While GnRHa therapy caused serum oestradiol levels to return to prepubertal levels in all 10 patients, serum IGF-I levels decreased only minimally after 1, 2 or 3 months of therapy (43.2 ± 5.6, 42.3 ± 6.4 and 44.1 ± 7.2 nmol/l respectively). Serum IGFBP-3 levels as determined using IRMA were also higher in CPP compared with age matched controls (4.70 ± 0.37 vs 3.71 ± 0.42 mg/l, P < 0.01). These differences were also evident when measured by WLB. GnRHa therapy caused a small and insignificant decrease in serum IGFBP-3 levels after 1, 2 or 3 months of therapy (4.57 ± 0.33, 4.48 ± 0.4 and 4.42 ± 0.3 mg/l respectively). Conclusions. The lack of suppression of both IGF-I and IGFBP-3, despite therapy which halts puberty and slows growth velocity, suggests that steroids may be involved in the induction of changes in the GH/IGF-I axis but not in their subsequent maintenance.