Long-term effects of insulin-like growth factor (IGF)-I treatment on serum IGFs and IGF binding proteins in adolescent patients with growth hormone receptor deficiency

Objective. The aim of this investigation was to study the effect of relatively high dose IGF-I therapy given for several months, on serum levels of IGF-I, IGF-II and IGFBP-3, and on IGF-I pharmacokinetics in patients with growth hormone insensitivity due to GH receptor dysfunction. Design and patients. Two adolescent subjects from Ecuador were treated with recombinant IGF-I at a dosage of 120 μg/kg s.c. twice daily, in combination with a GnRH analogue for 8 months. Measurements. Serum was sampled at baseline and at 3-8 months, for determination of IGF-I, IGF-II and IGFBP-3 by radioimmunoassay, and for evaluation of IGFBPs and IGFBP-3 protease activity by Western ligand blot and protease assay, respectively. Results. Peak serum IGF-I levels ranged from 272 to 492 μg/l. Mean serum IGF-II levels were decreased concurrently with the increase in IGF-I. Serum IGFBP-3 levels failed to rise with prolonged IGF-I treatment. There was no apparent change in the half-life of IGF-I during the treatment period. Conclusions. IGF administration does not increase serum levels of IGFBP-3 or significantly alter IGF-I pharmacokinetics.