Dose-Dependent Effect of Growth Hormone on Final Height in Children with Short Stature without Growth Hormone Deficiency

Context: The effect of GH therapy in short non-GH-deficient children, especially those with idiopathic short stature (ISS), has not been clearly established owing to the lack of controlled trials continuing until final height (FH). Objective: The aim of the study was to investigate the effect on growth to FH of two GH doses given to short children, mainly with ISS, compared with untreated controls. Design and Setting: A randomized, controlled, long-term multicenter trial was conducted in Sweden. Intervention: Two doses of GH (Genotropin) were administered, 33 or 67 mu g/kg.d; control subjects were untreated. Subjects: A total of 177 subjects with short stature were enrolled. Of these, 151 were included in the intent to treat (All(ITT)) population, and 108 in the per protocol (All(PP)) population. Analysis of ISS subjects included 126 children in the ITT (ISSITT) population and 68 subjects in the PP (ISSPP) population. Main Outcome Measures: We measured FH SD score (SDS), difference in SDS to midparenteral height (diff MPHSDS), and gain in height(SDS). Results: After 5.9 +/- 1.1 yr on GH therapy, the FHSDS in the All(PP) population treated with GH vs. controls was -1.5 +/- 0.81 (33 mu g/kg.d, -1.7 +/- 0.70; and 67 mu g/kg.d, -1.4 +/- 0.86; P = 0.032), vs. -2.4 +/- 0.85 (P < 0.001); the diff MPHSDS was -0.2 +/- 1.0 vs. -1.0 +/- 0.74 (P < 0.001); and the gain in height(SDS) was 1.3 +/- 0.78 vs. 0.2 +/- 0.69 (P < 0.001). GH therapy was safe and had no impact on time to onset of puberty. A dose-response relationship identified after 1 yr remained to FH for all growth outcome variables in all four populations. Conclusion: GH treatment significantly increased FH in ISS children in a dose- dependent manner, with a mean gain of 1.3 SDS (8 cm) and a broad range of response from no gain to 3 SDS compared to a mean gain of 0.2 SDS in the untreated controls. (J Clin Endocrinol Metab 93: 4342-4350, 2008)