Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children
2012 (English)In: BMC Endocrine Disorders, ISSN 1472-6823, Vol. 12, 26- p.Article in journal (Refereed) Published
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 mu g/kg/day (n=87) and (b) fixed GH dose of 43 mu 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% Delta 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) mu g/kg/day for Delta left ventricular diastolic diameter (cm), 39(+/- 24.5) mu g/kg/day for Delta alkaline phosphatase (mu kat/L), 47(+/- 43.5) mu g/kg/day for Delta lean soft tissue (SDS), 48(+/- 35.7) mu g/kg/day for Delta insulin (mU/L), 51(+/- 47.6) mu g/kg/day for Delta height (SDS), and 57(+/- 52.7) mu g/kg/day for Delta insulin-like growth factor I (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no dose-response effect for Delta fat mass (SDS) or Delta 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.
Place, publisher, year, edition, pages
2012. Vol. 12, 26- p.
GH deficiency, GH sensitivity, GH responsiveness, Idiopathic short stature, GH dose-effect, Metabolic effects, Lipolysis
IdentifiersURN: urn:nbn:se:umu:diva-64969DOI: 10.1186/1472-6823-12-26ISI: 000313279200001OAI: oai:DiVA.org:umu-64969DiVA: diva2:608070