IGF-1 and growth response to adult height in a randomized GH treatment trial in short non-GH-deficient children

Abstract

Context: GH treatment significantly increased adult height (AH) in a dose-dependent manner in short non-GH-deficient children in a randomized, controlled, clinical trial; the mean gain in height SD score (height SDS) was 1.3 (range 0-3), compared with 0.2 in the untreated group. Objective: The objective of the study was to analyze the relationship between IGF-1SDS, IGF binding protein-3 SDS (IGFBP3SDS), and their ratioSDS with a gain in the heightSDS until AH in non-GHdeficient short children. Design and Setting: This was a randomized, controlled, multicenter clinical trial. Intervention: The intervention included GH treatment: 33 or 67 μg/kg · d plus untreated controls. Subjects: One hundred fifty-one non-GH-deficient short children were included in the intent-totreat (ITT) population and 108 in the per-protocol (PP) population; 112 children in the ITT and 68 children in the PP populations had idiopathic short stature (ISS). Main Outcome Measures: Increments from baseline to on-treatment study mean IGF-1SDS (ΔIGF- 1SDS), IGFBP3 SDS, and IGF-1 to IGFBP3 ratioSDS were assessed in relationship to the gain in heightSDS. Results: Sixty-two percent of the variance in the gain in heightSDS in childrenonGHtreatment could be explained by four variables: ΔIGF-1SDS (explaining 28%), bone age delay, birth length (the taller the better), andGHdose (the higher the better). The lower IGF-1SDS was at baseline, the higher was its increment during treatment. For both the AllPP- and the ISS PP-treated groups, the attained IGF-1SDS study level did not correlate with height gain. Conclusion: In short non-GH-deficient children, the GH dose-related increment in IGF-1SDS from baseline to mean study level was the most important explanatory variable for long-term growth response from the peripubertal period until AH, when IGF-1SDS, IGFBP3 SDS, and their ratioSDS were compared concurrently. Copyright © 2014 by the Endocrine Society.