THE IGF-I/IGFBP-3 RATIO INCREASES DURING NORMAL AND PRECOCIOUS PUBERTY: AN INDEX OK FREE IGF-I?

Abstract

Serum IGF-I and IGFBP-3 are stimulated by the increase of pulsatile GH secretion and GH levels during puberty with a subsequent fall in adulthood. In children with chronic renal failure, changes in the IGF-I/IGFBP-3 ratio correlated to their growth retardation. However, the individual IGF-I/IGFBP-3 ratio has not previously been described in healthy children during puberty and in patients with central precocious puberty (CPP).Materials and methods: 926 healthy children (0-20 years) and 23 girls with CPP (2-9 years) before and afler 2 years of treatment with GnRH analogue and cyproterone acetate participated. Serum IGF-I and IGFBP-3 were analyzed with specific RIA's.Results: In healthy children serum IGF-I and IGFBP-3 increased significantly with age and pubertal maturation. When age and puberty was taken into account, no significant sex difference was detectable. The IGF-I/IGFBP-3 ratio increased with age and puberty from a prepubertal mean (+/−SD) of 0.065 (+/−0.025) to a maximum of 0.107 (+/−0.022) (p<0.0001) in Tanner stage IV. Compared to healthy children of the same age, girls with CPP had an increased IGF-I/BP-3 ratio of 0.095 (+/−0.026). After treatment IGF-I/IGFBP-3 ratio Standard Deviation Score (SDS) for CA decreased significantly, but did not normalize.Conclusion: The IGF-I/IGFBP-3 ratio increases in normal and precocious puberty concomitant with increased growth velocity. Gonadal suppression in CPP reduced height velocity which was reflected by a decrease in the IGF-I/IGFBP-3 ratio. Thus, we suggest that the individual IGF-I/IGFBP3 ratio may be an index of biologically active free IGF-I.