Idiopathic short stature: Will genetics influence the choice between GH and IGF-I therapy?

Martin O. Savage, Cecilia Camacho-Hübner, Alessia David, Louise A. Metherell, Vivian Hwa, Ron G. Rosenfeld, Adrian J.L. Clark

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Background: Idiopathic short stature (ISS) includes a range of conditions. Some are caused by defects in the GH-IGF-I axis. ISS is an approved indication for GH therapy in the USA and a similar approval in Europe may be imminent. Genetic analysis for single-gene defects has made enormous contributions to understanding the physiology of growth regulation. Can this type of investigation help in predicting growth responses to GH or IGF-I therapy? Methods: The rationale for choice of GH or IGF-I therapy in ISS is reviewed. Many ISS patients have low IGF-I, but most can generate IGF-I levels in response to short-term GH administration. Some GH resistance seems to be present. Mutation analysis in several cohorts of GHIS and ISS patients is reviewed. Results: Low IGF-I levels suggest either unrecognised GH deficiency or GH resistance. In classical GHIS patients, there was a positive relationship between IGFBP-3 levels and height SDS. No relationship exists between mutations and phenotype. There is a wide variability of phenotype in patients carrying identical mutations. Heterozygous GH receptor (GHR) mutations were present in < 5% of ISS patients and their role in causing growth defects is questionable. Exceptions are dominant negative mutations that have been shown to disturb growth. Conclusions: Analysis for single-gene defects does not give sensitive predictions of phenotype and cannot predict responses to GH or IGF-I therapy. Endocrine abnormalities have closer correlations with phenotype and may thus be a better guide to therapeutic responsiveness.

Original languageEnglish (US)
Pages (from-to)S33-S37
JournalEuropean journal of endocrinology
Volume157
Issue numberSUPPL. 1
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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