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


METHODS
This was a randomized, controlled, multicenter clinical trial.


METHODS
The intervention included GH treatment: 33 or 67 μg/kg · d plus untreated controls.


METHODS
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).


METHODS
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.


CONCLUSIONS
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.
Department of Clinical Science (B.K., E.L.), Pediatrics, Umeå University, SE-90185 Umeå, Sweden; Department of Women's and Children's Health (B.J.), Uppsala University, SE-75185 Uppsala, Sweden; and Göteborg Pediatric Growth Research Center (B.K., K.A.-W.), Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, SE-41685 Gothenburg, Sweden.
Berit
B
Kriström
Elena
E
Lundberg
Björn
B
Jonsson
Kerstin
K
Albertsson-Wikland
D000293:Adolescent; D000328:Adult; D001827:Body Height / Q000187:drug effects*; D002648:Child; D002657:Child Development / Q000187:drug effects*; D004392:Dwarfism / Q000097:blood / Q000188:drug therapy*; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D016896:Treatment Outcome
D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I