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

BMC Endocrine Disorders

Jovanna Dahlgren¹  Kerstin Albertsson-Wikland¹  Jan Gustafsson³  Andreas FM Nierop⁴  Berit Kriström²  Anders Nygren¹  Ralph Decker¹ 

[1] Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;Institute of Clinical Sciences, Department of Pediatrics, Umeå University, Umeå, Sweden;Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden;Muvara bv, Multivariate Analysis of Research Data, Leiderdorp, Netherlands

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

Others  :  1086112
DOI  :  10.1186/1472-6823-12-26

 received in 2012-06-13, accepted in 2012-10-11,  发布年份 2012

【 摘 要 】

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 nodose–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.

【 授权许可】

   
2012 Decker et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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Figure 3.

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