title: Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children.
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.
  
  
  OBJECTIVE
  There are different dose-dependent thresholds for metabolic effects in response to GH treatment.
  
  
  METHODS
  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.
authors.affiliation: Göteborg Pediatric Growth Research Centre (GP-GRC), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. Ralph.Decker@vgregion.se.
authors.forename: Ralph
authors.initials: R
authors.lastname: Decker
authors.forename: Anders
authors.initials: A
authors.lastname: Nygren
authors.forename: Berit
authors.initials: B
authors.lastname: Kriström
authors.forename: Andreas Fm
authors.initials: AF
authors.lastname: Nierop
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Albertsson-Wikland
authors.forename: Jovanna
authors.initials: J
authors.lastname: Dahlgren