Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal childrenReport as inadecuate

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BMC Endocrine Disorders

, 12:26

First Online: 01 November 2012Received: 13 June 2012Accepted: 11 October 2012


BackgroundIn 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 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.

ResultsDifferent 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.

ConclusionsDose-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.

KeywordsGH deficiency GH sensitivity, GH responsiveness Idiopathic short stature GH dose-effect Metabolic effects Lipolysis AbbreviationsALPAlkaline phosphatase

ANOVAAnalysis of variance

Apo A-IIApolipoprotein A-II

BMCBone mineral content

BMDBone mineral density


ED 50%Effective dose 50%

DBPDiastolic blood pressure

DXADual-energy X-ray absorptiometry

DPX-LProper name of the Lunar pencil beam scanner

GHGrowth hormone

GHDGrowth hormone deficiency

GP-GRCGöteborg Pediatric Growth Research Center

HbA1cGlycosylated haemoglobin

HDLHigh-density lipoprotein

HOMAHomeostasis model assessment of insulin resistance calculated as fasting serum insulin* fasting plasma glucose-22.5

IGF-IInsulin-like growth factor I

ISSIdiopathic short stature

IVSdInterventricular septal thickness in diastole

LDLLow-density lipoprotein

LpaLipoprotein a

LSTLean soft tissue

LVDdLeft ventricular diameter in diastole

LVMLeft ventricular mass

LVPWdLeft ventricular posterior wall in diastole

SBPSystolic blood pressure

SDSStandard deviation score.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6823-12-26 contains supplementary material, which is available to authorized users.

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