Twelve children with extreme, non-growth hormone (GH)-deficient short stature were treated for six months with recombinant human insulin-like growth factor-I (rhIGF-I) 100 μg/kg subcutaneously twice daily and for six months with placebo (with a three-month washout period in between) in a randomized, double-blind fashion to evaluate the effect of rhIGF-I treatment on growth. Growth velocity was significantly greater during rhIGF-I compared to placebo(6.4 ± 0.5 vs. 4.0 ± 0.5 cm/yr, p = 0.004), while rate of bone maturation (ΔBA/ΔCA) was not significantly different (1.3 ± 0.3 on rhIGF-I vs. 0.8 ± 0.2 on placebo, p = 0.237).

To determine whether acute administration of rhIGF-I suppresses GH secretion, 13 children with extreme, non-GH-deficient short stature were given 100 μg/kg of rhIGF-I subcutaneously on one morning and placebo on another morning (randomized order, double-blind, with at least one day of washout between). Growth hormone was sampled every 30 minutes (starting immediately prior to rhIGF-I or placebo injection) for 24 hours on each treatment day, and growth hormone-binding protein (GHBP) and insulin-like growth factor binding protein 3 (IGFBP3) were measured every six hours. There was no significant difference in GHBP or IGFBP3 levels between rhIGF-I and placebo. Mean 24-hour growth hormone was significantly decreased with rhIGF-I administration compared to placebo (1.5 ± 0.2 vs. 2.1 ± 0.2 ng/dL, p = 0.02). Growth hormone peak frequency was not significantly different between the treatments, but peak amplitude was decreased in the rhIGF-I group (7.1± 0.9 vs. 14.7 ± 3.6 ng/dL, p = 0.06).

We conclude that rhIGF-I administration significantly increases growth velocity in children with non-GH-deficient short stature. In addition, acute administration of rhIGF-I decreases mean 24-hour growth hormone level and growth hormone peak amplitude without significantly altering the peak frequency.