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Licensed Unlicensed Requires Authentication Published by De Gruyter January 18, 2017

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

Lucia Schena, Cristina Meazza, Sara Pagani, Valeria Paganelli, Elena Bozzola, Carmine Tinelli, Fabio Buzi and Mauro Bozzola

Abstract

Background:

In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.

Methods:

We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.

Results:

During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).

Conclusions:

In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.


Corresponding author: Mauro Bozzola, Professor, Dipartimento di Medicina Interna e Terapia Medica, Unità di Pediatria e Adolescentologia, Università degli Studi di Pavia, Fondazione IRCCS San Matteo, Piazzale C. Golgi 19, 27100 Pavia, Italy, Phone: +39 0382 501270, Fax: +39 0382 502876

Acknowledgments

The authors are grateful to Susan West for revising the English of the paper.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Lee MM. Idiopathic short stature. N Engl J Med 2014;354: 2576–82.10.1056/NEJMcp060828Search in Google Scholar

2. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 2008;93:4210–7.10.1210/jc.2008-0509Search in Google Scholar

3. Topor LS, Feldman HA, Bauchner H, Cohen LE. Variation in methods of predicting adult height for children with idiopathic short stature. Pediatrics 2010;126:938–44.10.1542/peds.2009-3649Search in Google Scholar

4. McCaughey ES, Mulligan J, Voss LD, Betts PR. Randomised trial of growth hormone in short normal girls. Lancet 1998;351:940–4.10.1016/S0140-6736(05)60604-6Search in Google Scholar

5. Leschek EW, Rose SR, Yanovski JA, Troendle JF, Quigley CA, et al. Growth Hormone Collaborative Group. 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;89:3140–8.10.1210/jc.2003-031457Search in Google Scholar

6. Albertsson-Wikland K, Aronson AS, Gustafsson J, Hagenäs L, Ivarsson SA, et al. Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency. J Clin Endocrinol Metab 2008;93:4342–50.10.1210/jc.2008-0707Search in Google Scholar

7. Wit JM, Boersma B, de Muinck Keizer-Schrama SM, Nienhuis HE, Oostdijk W, 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;42:365–72.10.1111/j.1365-2265.1995.tb02644.xSearch in Google Scholar

8. Kawai M, Momoi T, Yorifuji T, Yamanaka C, Sasaki H, et al. Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency. J Pediatr 1997;130:205–9.10.1016/S0022-3476(97)70344-5Search in Google Scholar

9. Travaglino P, Buzi F, Meazza C, Pagani S, Tinelli C, et al. Response to long-term growth hormone therapy in short children with reduced GH bioactivity. Horm Res 2006;66:189–94.10.1159/000094483Search in Google Scholar

10. Pagani S, Meazza C, Laarej K, Cantoni F, Bozzola M. Efficacy of long-term growth hormone (GH) therapy in short children with reduced GH biological activity. J Endocrinol Invest 2011;34: 366–9.10.1007/BF03347461Search in Google Scholar

11. Elmlinger MW, Kühnel W, Weber MM, Ranke MB. Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3). Clin Chem Lab Med 2004;42:654–64.10.1515/CCLM.2004.112Search in Google Scholar

12. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab 2000;85:3990–3.10.1210/jc.85.11.3990Search in Google Scholar

13. Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 1976;51:170–9.10.1136/adc.51.3.170Search in Google Scholar

14. Nota AIFA 39, Gazzetta Ufficiale della Repubblica Italiana del 16/01/2001.Search in Google Scholar

15. Hindmarsh PC, Brook CG. Effect of growth hormone on short normal children. Br Med J 1987;295:573–7.10.1136/bmj.295.6598.573Search in Google Scholar

16. 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;37:150–5.10.1159/000182300Search in Google Scholar

17. Bang P, Ahmed SF, Argente J, Backeljauw P, Bettendorf M, et al. Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol (Oxf) 2012;77:169–81.10.1111/j.1365-2265.2012.04420.xSearch in Google Scholar

18. Ocaranza P, Gaete X, Román R, Morales F, Íñiguez G, et al. Phosphotyrosine phosphatases in GH-stimulated skin fibroblasts from children with idiopathic short stature. J Pediatr Endocrinol Metab 2013;26:833–840.10.1515/jpem-2013-0044Search in Google Scholar

19. Pagani S, Petkovic V, Messini B, Meazza C, Bozzola E, et al. Heterozygous GHR gene mutation in a child with idiopathic short stature. J Pediatr Endocrinol Metab 2014;27:329–34.10.1515/jpem-2013-0359Search in Google Scholar

20. Buchlis JG, Irizarry L, Crotzer BC, Shine BJ, Allen L, et al. Comparison of final heights of growth hormone-treated vs. untreated children with idiopathic growth failure. J Clin Endocrinol Metab 1998;83:1075–9.10.1210/jcem.83.4.4703Search in Google Scholar

21. Hintz RL, Attie KM, Baptista J, Roche A. Effect of growth hormone treatment on adult height of children with idiopathic short stature. Genentech Collaborative Group. N Engl J Med 1999;340:502–7.10.1056/NEJM199902183400702Search in Google Scholar

22. López-Siguero JP, García-Garcia E, Carralero I, Martínez-Aedo MJ. Adult height in children with idiopathic short stature treated with growth hormone. J Pediatr Endocrinol Metab 2000;13:1595–602.10.1515/JPEM.2000.13.9.1595Search in Google Scholar

23. Jeong HR, Shim YS, Lee HS, Hwang JS. The effect of growth hormone treatment on height in children with idiopathic short stature. J Pediatr Endocrinol Metab 2014;27:629–33.10.1515/jpem-2013-0461Search in Google Scholar

24. Wit JM, Rekers-Mombarg LT, Dutch Growth Hormone Advisory Group. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab 2002;87:604–11.10.1210/jcem.87.2.8225Search in Google Scholar

25. Hindmarsh PC, Brook CG. Final height of short normal children treated with growth hormone. Lancet 1996;348:13–6.10.1016/S0140-6736(96)01038-0Search in Google Scholar

Received: 2016-7-25
Accepted: 2016-11-28
Published Online: 2017-1-18
Published in Print: 2017-2-1

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