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Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children
Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands.
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2012 (English)In: BMC Endocrine Disorders, ISSN 1472-6823, Vol. 12, 26- p.Article in journal (Refereed) Published
Abstract [en]

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 mu g/kg/day (n=87) and (b) fixed GH dose of 43 mu g/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% Delta 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) mu g/kg/day for Delta left ventricular diastolic diameter (cm), 39(+/- 24.5) mu g/kg/day for Delta alkaline phosphatase (mu kat/L), 47(+/- 43.5) mu g/kg/day for Delta lean soft tissue (SDS), 48(+/- 35.7) mu g/kg/day for Delta insulin (mU/L), 51(+/- 47.6) mu g/kg/day for Delta height (SDS), and 57(+/- 52.7) mu g/kg/day for Delta insulin-like growth factor I (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no dose-response effect for Delta fat mass (SDS) or Delta 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.

Place, publisher, year, edition, pages
2012. Vol. 12, 26- p.
Keyword [en]
GH deficiency, GH sensitivity, GH responsiveness, Idiopathic short stature, GH dose-effect, Metabolic effects, Lipolysis
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URN: urn:nbn:se:umu:diva-64969DOI: 10.1186/1472-6823-12-26ISI: 000313279200001OAI: diva2:608070
Available from: 2013-02-26 Created: 2013-02-04 Last updated: 2013-02-26Bibliographically approved

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