Open Access Research article

Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children

Ralph Decker1*, Anders Nygren1, Berit Kriström2, Andreas FM Nierop3, Jan Gustafsson4, Kerstin Albertsson-Wikland1 and Jovanna Dahlgren1

Author Affiliations

1 Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

2 Institute of Clinical Sciences, Department of Pediatrics, Umeå University, Umeå, Sweden

3 Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands

4 Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

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BMC Endocrine Disorders 2012, 12:26  doi:10.1186/1472-6823-12-26

Published: 1 November 2012



In addition to stimulating linear growth in children, growth hormone (GH) influences metabolism and body composition. These effects should be considered when individualizing GH treatment as dose-dependent changes in metabolic markers have been reported. Hypothesis: There are different dose-dependent thresholds for metabolic effects in response to GH treatment.


A randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2-year catch-up growth period, with two treatment regimens (a) individualized GH dose including six different dose groups ranging from 17–100 μg/kg/day (n=87) and (b) fixed GH dose of 43 μg/kg/day (n=41). The individualized GH dose group was used for finding dose–response effects, where the effective GH dose (ED 50%) required to achieve 50% Δ effect was calculated with piecewise linear regressions.


Different thresholds for the GH dose were found for the metabolic effects. The GH dose to achieve half of a given effect (ED 50%, with 90% confidence interval) was calculated as 33(±24.4) μg/kg/day for Δ left ventricular diastolic diameter (cm), 39(±24.5) μg/kg/day for Δ alkaline phosphatase (μkat/L), 47(±43.5) μg/kg/day for Δ lean soft tissue (SDS), 48(±35.7) μg/kg/day for Δ insulin (mU/L), 51(±47.6) μg/kg/day for Δ height (SDS), and 57(±52.7) μg/kg/day for Δ insulin-like growth factor I (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no dose–response effect for Δ fat mass (SDS) or Δ leptin ng/ml in the dose range studied. None of the metabolic effects presented here were related to the dose selection procedure in the trial.


Dose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive. The level of insulin was more responsive than that of IGF-I, with the threshold effect for height in the interval between.

GH deficiency; GH sensitivity, GH responsiveness; Idiopathic short stature; GH dose-effect; Metabolic effects; Lipolysis