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Background  Responsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height.    Methods  A multicentre, randomized, clinical trial (TRN88-177) in 104 children (90 boys), who had received GH 33 μg/kg/day during at least 1 prepubertal year. They were followed from GH start to adult height (mean, 7.5 years; range, 4.6–10.7). At onset of puberty, children were randomized into three groups, to receive 67 μg/kg/day (GH 67 ) given once (GH 67x1 ;  n  = 30) or divided into two daily injection (GH 33x2 ;  n  = 36), or to remain on a single 33 μg/kg/day dose (GH 33x1 ;  n  = 38). The outcome measures were change and obtained mean on-treatment IGF-I SDS , IGFBP3 SDS  and IGF-I/IGFBP3 ratio SDS  during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in height SDS .    Results  Mean prepubertal increases 1 year after GH start were: 2.1 IGF-I SDS , 0.6 IGFBP3 SDS  and 1.5 IGF-I/IGFBP3ratio SDS . A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in height SDS . During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-I SDS  was higher in GH 67  vs GH 33  ( p  = 0.031). First year pubertal ∆IGF-I SDS  was significantly higher in the GH 67 vs GH 33  group (0.5 vs −0.1, respectively,  p  = 0.007), as well as ∆IGF-I SDS  to the pubertal mean level (0.2 vs −0.2,  p  = 0.028). In multivariate analyses, the prepubertal increase in ‘∆IGF-I SDS  from GH start’ and the ‘GH dose-dependent pubertal ∆IGF-I SDS ’ were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in height SDS .    Trial registration  TRN 88–177, not applicable 1988.    Conclusion  The dose-dependent change in IGFs was related to a dose-dependent pubertal gain in height SDS . The attempt to mimic normal physiology by giving a higher GH dose during puberty was associated with both an increase in IGF-I and a dose-dependent gain in height SDS .    Electronic supplementary material  The online version of this article (doi:10.1186/s12902-015-0080-8) contains supplementary material, which is available to authorized users.

Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain