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Growth hormone (GH) dose-dependent IGF-I response relates to pubertal height gain
Umea Univ, Inst Clin Sci Pediat, SE-90185 Umea, Sweden..
Umea Univ, Inst Clin Sci Pediat, SE-90185 Umea, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol Endocrinol, SE-40530 Gothenburg, Sweden..
2015 (English)In: BMC Endocrine Disorders, ISSN 1472-6823, E-ISSN 1472-6823, Vol. 15, 84Article in journal (Refereed) Published
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Abstract [en]

Background: Responsiveness to GH treatment can be estimated by both growth and Delta 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 mu g/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 mu g/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 mu g/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 Delta 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 GH67 vs GH(33) (p = 0.031). First year pubertal Delta IGF-I-SDS was significantly higher in the GH(67) vs GH33 group (0.5 vs -0.1, respectively, p = 0.007), as well as Delta IGF-I-SDS to the pubertal mean level (0.2 vs -0.2, p = 0.028). In multivariate analyses, the prepubertal increase in 'Delta IGF-I-SDS from GH start' and the 'GH dose-dependent pubertal Delta IGF-I-SDS' were the most important variables for explaining variation in prepubertal (21 %), pubertal (26 %) and total (28 %) gain in height(SDS). 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).

Place, publisher, year, edition, pages
2015. Vol. 15, 84
Keyword [en]
Gain in height, IGF-I increment, IGF-I level, IGFBP3, Ratio IGF-I/IGFBP3, GH dose-dependent pubertal IGF-I response
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-274443DOI: 10.1186/s12902-015-0080-8ISI: 000367051700001PubMedID: 26682747OAI: oai:DiVA.org:uu-274443DiVA: diva2:896480
Funder
Swedish Research Council, 7509
Available from: 2016-01-21 Created: 2016-01-21 Last updated: 2017-11-30Bibliographically approved

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