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Different thresholds of tissue-specific dose-responses to growth... » Isaúde
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BMC Endocrine Disorders
2012-11-02 02:22:15

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

Descrição: 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.MethodA 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.

Identificador: doi:10.1186/1472-6823-12-26
Volume: 0
Página: 2 a


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