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  • Title: IGF-1 and growth response to adult height in a randomized GH treatment trial in short non-GH-deficient children.
    Author: Kriström B, Lundberg E, Jonsson B, Albertsson-Wikland K, study group.
    Journal: J Clin Endocrinol Metab; 2014 Aug; 99(8):2917-24. PubMed ID: 24823461.
    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 (heightSDS) 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-GH-deficient 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-to-treat (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), IGFBP3SDS, 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 children on GH treatment could be explained by four variables: ΔIGF-1SDS (explaining 28%), bone age delay, birth length (the taller the better), and GH dose (the higher the better). The lower IGF-1SDS was at baseline, the higher was its increment during treatment. For both the AllPP- and the ISSPP-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, IGFBP3SDS, and their ratioSDS were compared concurrently.
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