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 < 001). These differences were also when measured by WLB. evident 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.