Effect of Growth Hormone Treatment on Adult Height in Peripubertal Children with Idiopathic Short Stature: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

GH is often used to treat children with idiopathic short stature despite the lack of definitive, long-term studies of efficacy. We performed a randomized, double-blind, placebo-controlled trial to determine the effect of GH on adult height in peripubertal children. Subjects (n = 68; 53 males and 15 females), 9-16 yr old, with marked, idiopathic short stature [height or predicted height < or = -2.5 sd score (SDS)] received either GH (0.074 mg/kg) or placebo sc three times per week until they were near adult height. At study termination, adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr. Adult height was greater in the GH-treated group (-1.81 +/- 0.11 SDS, least squares mean +/- sem) than in the placebo-treated group (-2.32 +/- 0.17 SDS) by 0.51 SDS (3.7 cm; P < 0.02; 95% confidence interval, 0.10-0.92 SDS). A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS. Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS (0.52 SDS; 3.8 cm; P < 0.001; 95% confidence interval, 0.22-0.82 SDS) and no important dropout bias. In conclusion, GH treatment increases adult height in peripubertal children with marked idiopathic short stature.

Can we increase adolescent growth?

“…Other studies have addressed similar questions and have obtained quite similar results (33,34). Altogether, these results demonstrate that GH given alone can increase the pubertal growth spurt in short adolescents.…”

The Effect of Growth Hormone Treatment on Adult Height of Children With Idiopathic Short Stature: A Systematic Review and Meta-Analyses

“…Twenty studies related to the effect of treatment with growth hormone on the adult height of children with ISS with a total sample size of 1,517 were included in the meta-analysis ( Fig. 1 and Table 1 [10,11,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] When results of studies were combined using random effects model, SMD for treatment start height was -1.64 (95% CI: -2.01 to -1.28) which is equal to 5% (their height was higher than 5% of participants) (Fig. 3).…”

Pharmacogenomics and pharmacoproteomics in the evaluation and management of short stature

“…Secondary IGFD has thus been associated with a variety of genetic, developmental defects in pituitary development and GH secretion, while primary IGFD has been observed with molecular defects involving the GH receptor (GHR), the GHR signaling cascade, and the IGF-I gene itself. Since studies suggest that at least 25% of children labeled as ISS have low serum IGF-I, despite apparently normal GH secretion, these rare genetic causes of primary IGFD, at least in their classical form, are likely to account for only a small percentage of patients identified as primary IGFD (2,3,5,6). A further explanation for such cases is necessary, and possibilities include: i) heterozygosity for specific mutations affecting the GH-IGF axis, accompanied by inadequate compensation at the level of GH production or IGF-I gene transcription and production; ii) polymorphisms of known genes of the GH-IGF axis, affecting their transcription or translation; iii) defects involving genes as yet unidentified; or iv) combinations of the factors listed above.…”