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

ABSTRACT:

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

SUBMITTER: Decker R 

PROVIDER: S-EPMC3583138 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature