%0 Journal Article
%T Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children
%A Decker Ralph
%A Nygren Anders
%A Kristr£¿m Berit
%A Nierop Andreas FM
%J BMC Endocrine Disorders
%D 2012
%I BioMed Central
%R 10.1186/1472-6823-12-26
%X 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¨C100 ¦Ìg/kg/day (n=87) and (b) fixed GH dose of 43 ¦Ìg/kg/day (n=41). The individualized GH dose group was used for finding dose¨Cresponse effects, where the effective GH dose (ED 50%) required to achieve 50% ¦¤ 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(¡À24.4) ¦Ìg/kg/day for ¦¤ left ventricular diastolic diameter (cm), 39(¡À24.5) ¦Ìg/kg/day for ¦¤ alkaline phosphatase (¦Ìkat/L), 47(¡À43.5) ¦Ìg/kg/day for ¦¤ lean soft tissue (SDS), 48(¡À35.7) ¦Ìg/kg/day for ¦¤ insulin (mU/L), 51(¡À47.6) ¦Ìg/kg/day for ¦¤ height (SDS), and 57(¡À52.7) ¦Ìg/kg/day for ¦¤ insulin-like growth factor I (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no dose¨Cresponse effect for ¦¤ fat mass (SDS) or ¦¤ 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.
%K GH deficiency
%K GH sensitivity
%K GH responsiveness
%K Idiopathic short stature
%K GH dose-effect
%K Metabolic effects
%K Lipolysis
%U http://www.biomedcentral.com/1472-6823/12/26