Prepubertal children with growth hormone deficiency treated for four years with growth hormone experience dose-dependent increase in height, but not in the rate of puberty initiation.

Background/aims: Limited data exist on long-term dose response to recombinant human growth hormone (rhGH) in prepubertal GH-deficient (GHD) children. The effect of low, intermediate, and high-dose rhGH (25, 50, and 100 μg/kg/day, respectively) on growth and puberty in children with GHD was investigated for 48 months.

Methods: A prospective, dose-response study in 111 patients (aged 3-16 years) evaluated growth velocity (cm/year), height standard deviation score (HSDS), corrected HSDS, bone age/chronologic age ratio, body mass index SDS, and the percentage starting puberty.

Results: Dose-related increases were observed in growth velocity (p < 0.001), HSDS (p < 0.001), and corrected HSDS (p < 0.001) from baseline to 48 months. Increases in the bone age/chronologic age ratio (p = 0.043) and body mass index SDS (p = 0.018) occurred up to 36 months at intermediate and high doses versus low-dose rhGH; increases at 48 months were not significant. No significant differences in growth were found between intermediate and high doses of rhGH. Percentages of rhGH-treated patients starting puberty at each dose were equivalent (p = 0.607).

Conclusions: rhGH, 50 and 100 μg/kg/day, induced greater growth than 25 μg/kg/day without altering the proportion of children starting puberty. The maximum approved dose for pubertal patients (100 μg/kg/day) is not required or recommended for prepubertal children with GHD.