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Decker R, Nygren A, Kriström B, et al. Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children. BMC Endocr Disord. 2012;12:26doi: 10.1186/1472-6823-12-26.
Decker, R., Nygren, A., Kriström, B., Nierop, A. F., Gustafsson, J., Albertsson-Wikland, K., & Dahlgren, J. (2012). Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children. BMC endocrine disorders, 1226. https://doi.org/10.1186/1472-6823-12-26
Decker, Ralph, et al. "Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children." BMC endocrine disorders vol. 12 (2012): 26. doi: https://doi.org/10.1186/1472-6823-12-26
Decker R, Nygren A, Kriström B, Nierop AF, Gustafsson J, Albertsson-Wikland K, Dahlgren J. Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children. BMC Endocr Disord. 2012 Nov 01;12:26. doi: 10.1186/1472-6823-12-26. PMID: 23116291; PMCID: PMC3583138.
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BMC Endocr Disord. 2012 Nov 01;12:26. doi: 10.1186/1472-6823-12-26.

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

BMC endocrine disorders

Ralph Decker, Anders Nygren, Berit Kriström, Andreas Fm Nierop, Jan Gustafsson, Kerstin Albertsson-Wikland, Jovanna Dahlgren

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. [email protected].

PMID: 23116291 PMCID: PMC3583138 DOI: 10.1186/1472-6823-12-26

Abstract

BACKGROUND: 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.

METHOD: 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.

RESULTS: 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.

CONCLUSIONS: 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.

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