Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Viewpoint
  • Published:

Which children with idiopathic short stature should receive growth hormone therapy?

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 118–119 (2008)Cite this article

To answer this question is a difficult task—the parameters necessary for precise evaluation of children with idiopathic short stature (ISS) are not yet clearly established. Before proposing which children with ISS should receive growth hormone (GH) therapy, therefore, I will discuss the possible etiology of ISS, and the efficacy and safety of the proposed treatment regimen.

Defining ISS is apparently simple: this definition includes a group of children who are short for unknown reasons. One must consider, however, that only a subset of children with ISS will be bona fide patients. Some children are short simply because their parents are short (i.e. hereditary or familial short stature). In other cases, no cause can be found, even after extensive investigation, and some clinicians consider such children normal. In addition, the height of some children described as 'short' might actually fall within the normal distribution (albeit at the low end), which suggests they too are without disease. For other children, however, the situation is not so simple. Stature is a complex trait linked to a large number of growth-modulatory genes. A genetic defect could, therefore, explain the short stature of some individuals. In the largest study published to date, Rappold et al.1 screened children with ISS for a mutation in the short stature homeobox (SHOX) gene and demonstrated that SHOX mutation accounts for 2.5% of all cases of ISS. Although the authors screened only a single gene, the results of this study confirm that an anomaly of one growth-regulatory gene is present in a population with short stature of unknown cause.1 Finally, the ambiguity inherent in the term 'ISS' is illustrated by Shanske et al., who reported on a “unique deletion in exon 5 of SHOX gene in a patient with idiopathic short stature”.2 If a cause is identified then, by definition, the term 'idiopathic' is no longer appropriate.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Rappold G et al. (2002) Deletions of the homeobox gene SHOX (short stature homeobox) are an important cause of growth failure in children with short stature. J Clin Endocrinol Metab 87: 1402–1406

    Article  CAS  PubMed  Google Scholar 

  2. Shanske AL et al. (2007) Unique deletion in exon 5 of SHOX gene in a patient with idiopathic short stature. Horm Res 67: 61–66

    CAS  PubMed  Google Scholar 

  3. Hintz RL et al. (1999) Effect of growth hormone treatment on adult height of children with idiopathic short stature. Genentech Collaborative Group. N Engl J Med 340: 502–507

    Article  CAS  PubMed  Google Scholar 

  4. Kemp SF et al. (2005) Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature. J Clin Endocrinol Metab 90: 5247–5253

    Article  CAS  PubMed  Google Scholar 

  5. Leschek EW et al. (2004) 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 89: 3140–3148

    Article  CAS  PubMed  Google Scholar 

  6. van Dijk M et al. (2007) Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (SGA) and untreated short SGA controls. J Clin Endocrinol Metab 92: 160–165

    Article  CAS  PubMed  Google Scholar 

  7. Ross JL et al. (2004) Psychological adaptation in children with idiopathic short stature treated with growth hormone or placebo. J Clin Endocrinol Metab 89: 4873–4878

    Article  CAS  PubMed  Google Scholar 

  8. Dickinson HO et al. (2007) Self-reported quality of life of 8–12-year-old children with cerebral palsy: a cross sectional European study. Lancet 369: 2171–2178

    Article  PubMed  Google Scholar 

  9. Ranke MB et al. (2007) Age at growth hormone therapy start and first-year responsiveness to growth hormone are major determinants of height outcome in idiopathic short stature. Horm Res 68: 53–62

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Hopital Necker Enfants Malades, 149 rue de Sevres, Paris 75015, France paul.czernichow@nck.aphp.fr

Authors and Affiliations

  1. P Czernichow is a Professor of Paediatrics and a Consultant in Endocrinology and Diabetes, Hopital Necker Enfants Malades, Paris, France.,

    Paul Czernichow

Authors
  1. Paul Czernichow
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

Dr Czernichow is a consultant for Ipsen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Czernichow, P. Which children with idiopathic short stature should receive growth hormone therapy?. Nat Rev Endocrinol 4, 118–119 (2008). https://doi.org/10.1038/ncpendmet0700

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncpendmet0700

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing