Abstract
BackgroundResponsiveness 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.MethodsA 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 (GH67) given once (GH67x1; n = 30) or divided into two daily injection (GH33x2; n = 36), or to remain on a single 33 μg/kg/day dose (GH33x1; n = 38). The outcome measures were change and obtained mean on-treatment IGF-ISDS, IGFBP3SDS and IGF-I/IGFBP3 ratioSDS during prepuberty and puberty. These variables were assessed in relation to prepubertal, pubertal and total gain in heightSDS.ResultsMean prepubertal increases 1 year after GH start were: 2.1 IGF-ISDS, 0.6 IGFBP3SDS and 1.5 IGF-I/IGFBP3ratioSDS. A significant positive correlation was found between prepubertal ∆IGFs and both prepubertal and total gain in heightSDS. During puberty changes in IGFs were GH dose-dependent: mean pubertal level of IGF-ISDS was higher in GH67 vs GH33 (p = 0.031). First year pubertal ∆IGF-ISDS was significantly higher in the GH67vs GH33 group (0.5 vs −0.1, respectively, p = 0.007), as well as ∆IGF-ISDS to the pubertal mean level (0.2 vs −0.2, p = 0.028). In multivariate analyses, the prepubertal increase in ‘∆IGF-ISDS from GH start’ and the ‘GH dose-dependent pubertal ∆IGF-ISDS’ were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in heightSDS.Trial registrationTRN 88–177, not applicable 1988.ConclusionThe dose-dependent change in IGFs was related to a dose-dependent pubertal gain in heightSDS. 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 heightSDS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12902-015-0080-8) contains supplementary material, which is available to authorized users.
Highlights
Responsiveness to growth hormone (GH) treatment can be estimated by both growth and ΔIGF-I
The dose-dependent change in Insulin-like growth factors (IGFs) was related to a dose-dependent pubertal gain in heightSDS
In children with low GH secretion diagnosed with idiopathic isolated GH deficiency (GHD) (IIGHD), we have reported that GH dosing, mimicking the physiological pubertal increase in GH secretion, has a dose-dependent effect on the gain in heightSDS until adult height (AH)
Summary
Responsiveness to GH treatment can be estimated by both growth and ΔIGF-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. Two studies reported results for multiple variables (IGF-I, IGFBP3 and their molar ratio). These were non-randomized, 1-year clinical trials in prepubertal children with and without GH deficiency (GHD) [8, 9]. They both observed an increase in IGFs during GH treatment as a sign of high GH sensitivity and treatment compliance. The relevance of the variables IGF-I, IGFBP3 and the IGF-I/IGFBP3 ratio in relation to prepubertal, pubertal and total gain in height has not been previously reported in GH-treated children
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