Recombinant Human Growth Hormone for Idiopathic Short Stature: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

GAO Lan ¹ , XU Jing ² , YANG Fan ³ ,  KANG Deying ⁴

1. Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China;2. Xinjin Maternal and Child Health Hospital, Chengdu 611430, China;3. West China Second University Hospital, Sichuan University, Chengdu 610041, China;4. Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

KANG Deying, Email: deyingkang@126.com

Keywords：

Recombinant human growth hormone; Idiopathic short stature; Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20120233

Video：

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Objective 　To evaluate long-term effectiveness of recombinant human growth hormone (rhGH) for children with idiopathic short stature (ISS).
Methods 　The randomized controlled trials (RCTs) about rhGH in treating ISS published from 1985 to 2010 were searched in PubMed, ScienceDirect, EBSCOHost, EMbase, The Cochrane Library, CBM, CNKI and VIP. According to the Cochrane Handbook, two reviewers independently screened literature, extracted data, assessed methodological quality, and conducted meta-analysis using RevMan 5.0 software.
Results 　A total of 11 RCTs involving 607 ISS children were included. The results of meta-analysis showed that, compared with the blank/placebo control group after 1-year treatment, the rhGH group resulted in a significant increase in height standard deviation score (SDS) (MD=0.29, 95%CI 0.03 to 0.54, P=0.03), growth velocity (MD=2.68 cm/year, 95%CI 1.70 to 3.65, P lt;0.000 01), and adult SDS (MD=0.46, 95%CI 0.29 to 0.63, P lt;0.000 01).
Conclusion 　rhGH can effectively promote the growth of ISS children. But due to the limitation of quality and small sample size of the included studies, its effectiveness still needs to be further proved by more high quality RCTs.

Citation： GAO Lan,XU Jing,YANG Fan,KANG Deying. Recombinant Human Growth Hormone for Idiopathic Short Stature: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2012, 12(12): 1516-1521. doi: 10.7507/1672-2531.20120233 Copy

1.	刘戈力. 特发性身材矮小. 中国实用儿科杂志, 2005, 20(8): 453-455.
2.	Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version5.1.2[updated March 2011], The Cochrane Collaboration, 2011. [2011-06-10] Available from: http://www.cochrane-handbook.org.
3.	Abrams KR, Gillies CL, Lambert PC. Meta-analysis of heterogeneously reported trials assessing change from baseline. Statistics in Medicine, 2005, 24(24): 3823-3844.
4.	Leschek EW, Rose SR, Yanovski JA, et al. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab, 2004, 89(7): 3140-3148.
5.	van Gool SA, Kamp GA, Odink RJ, et al. High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height. Eur J Endocrinol, 2010, 162(4): 653-660.
6.	Soliman AT, Khadir MMA. Growth parameters and predictors of growth in short children with and without growth hormone (GH) deficiency treated with human GH: a randomized controlled study. J Trop Pediatr, 1996, 42(5): 281-286.
7.	Coutant R, Rouleau S, Despert F, et al. Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings. J Clin Endocrinol Metab, 2001, 86(10): 4649-4654.
8.	Zadik Z, Mira U, Landau H. Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone. Horm Res, 1992, 37(4-5): 150-155.
9.	Wit JM, Boersma B, de Muinck Keizer-Schrama SM, et al. Long-term results of growth hormone therapy in children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group. Clin Endocrinol (Oxf), 1995, 42(4): 365-372.
10.	Buchlis JG, Irizarry L, Crotzer BC, et al. Comparison of final heights of growth hormone-treated vs. untreated children with idiopathic growth failure. J Clin Endocrinol Metab, 1998, 83(4): 1075-1079.
11.	van Gool SA, Kamp GA, Visser-van Balen H, et al. Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty. J Clin Endocrinol Metab, 2007, 92(4): 1402-1408.
12.	Genentech Collaborative Study Group. Idiopathic short stature: results of a one-year controlled study of human growth hormone treatment. J Pediatr, 1989, 115(5 Pt 1): 713-719.
13.	Rekers-Mombarg LT, Kamp GA, Massa GG, et al. Influence of growth hormone treatment on pubertal timing and pubertal growth in children with idiopathic short stature. Dutch Growth Hormone Working Group. J Pediatr Endocrinol Metab, 1999, 12(5): 611-622.
14.	Kamp GA, Waelkens JJ, de Muinck Keizer-Schrama SM, et al. High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature. Arch Dis Child, 2002, 87(3): 215-220.
15.	马祖祥, 易著文, 吴小川, 等. 环磷酰胺在难治性肾病综合征治疗中的应用——30年文献Meta 分析. 中华儿科杂志, 2002, 40(345): 342-435.

1. 刘戈力. 特发性身材矮小. 中国实用儿科杂志, 2005, 20(8): 453-455.
2. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version5.1.2[updated March 2011], The Cochrane Collaboration, 2011. [2011-06-10] Available from: http://www.cochrane-handbook.org.
3. Abrams KR, Gillies CL, Lambert PC. Meta-analysis of heterogeneously reported trials assessing change from baseline. Statistics in Medicine, 2005, 24(24): 3823-3844.
4. Leschek EW, Rose SR, Yanovski JA, et al. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab, 2004, 89(7): 3140-3148.
5. van Gool SA, Kamp GA, Odink RJ, et al. High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height. Eur J Endocrinol, 2010, 162(4): 653-660.
6. Soliman AT, Khadir MMA. Growth parameters and predictors of growth in short children with and without growth hormone (GH) deficiency treated with human GH: a randomized controlled study. J Trop Pediatr, 1996, 42(5): 281-286.
7. Coutant R, Rouleau S, Despert F, et al. Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings. J Clin Endocrinol Metab, 2001, 86(10): 4649-4654.
8. Zadik Z, Mira U, Landau H. Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone. Horm Res, 1992, 37(4-5): 150-155.
9. Wit JM, Boersma B, de Muinck Keizer-Schrama SM, et al. Long-term results of growth hormone therapy in children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch Growth Hormone Working Group. Clin Endocrinol (Oxf), 1995, 42(4): 365-372.
10. Buchlis JG, Irizarry L, Crotzer BC, et al. Comparison of final heights of growth hormone-treated vs. untreated children with idiopathic growth failure. J Clin Endocrinol Metab, 1998, 83(4): 1075-1079.
11. van Gool SA, Kamp GA, Visser-van Balen H, et al. Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty. J Clin Endocrinol Metab, 2007, 92(4): 1402-1408.
12. Genentech Collaborative Study Group. Idiopathic short stature: results of a one-year controlled study of human growth hormone treatment. J Pediatr, 1989, 115(5 Pt 1): 713-719.
13. Rekers-Mombarg LT, Kamp GA, Massa GG, et al. Influence of growth hormone treatment on pubertal timing and pubertal growth in children with idiopathic short stature. Dutch Growth Hormone Working Group. J Pediatr Endocrinol Metab, 1999, 12(5): 611-622.
14. Kamp GA, Waelkens JJ, de Muinck Keizer-Schrama SM, et al. High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature. Arch Dis Child, 2002, 87(3): 215-220.
15. 马祖祥, 易著文, 吴小川, 等. 环磷酰胺在难治性肾病综合征治疗中的应用——30年文献Meta 分析. 中华儿科杂志, 2002, 40(345): 342-435.

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Recombinant Human Growth Hormone for Idiopathic Short Stature: A Systematic Review

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