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, Ronald (Ron) Rosenfeld, Adrian J L Clark

Research output: Contribution to journalArticle

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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)
JournalEuropean Journal of Endocrinology
Volume157
Issue numberSUPPL. 1
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Insulin-Like Growth Factor I
Mutation
Phenotype
Inborn Genetic Diseases
Growth
Therapeutics
Insulin-Like Growth Factor Binding Protein 3

ASJC Scopus subject areas

  • Endocrinology

Cite this

Savage, M. O., Camacho-Hübner, C., David, A., Metherell, L. A., Hwa, V., Rosenfeld, R. R., & Clark, A. J. L. (2007). Idiopathic short stature: Will genetics influence the choice between GH and IGF-I therapy? European Journal of Endocrinology, 157(SUPPL. 1). https://doi.org/10.1530/EJE-07-0292

Idiopathic short stature : Will genetics influence the choice between GH and IGF-I therapy? / Savage, Martin O.; Camacho-Hübner, Cecilia; David, Alessia; Metherell, Louise A.; Hwa, Vivian; Rosenfeld, Ronald (Ron); Clark, Adrian J L.

In: European Journal of Endocrinology, Vol. 157, No. SUPPL. 1, 08.2007.

Research output: Contribution to journalArticle

Savage, MO, Camacho-Hübner, C, David, A, Metherell, LA, Hwa, V, Rosenfeld, RR & Clark, AJL 2007, 'Idiopathic short stature: Will genetics influence the choice between GH and IGF-I therapy?', European Journal of Endocrinology, vol. 157, no. SUPPL. 1. https://doi.org/10.1530/EJE-07-0292
Savage MO, Camacho-Hübner C, David A, Metherell LA, Hwa V, Rosenfeld RR et al. Idiopathic short stature: Will genetics influence the choice between GH and IGF-I therapy? European Journal of Endocrinology. 2007 Aug;157(SUPPL. 1). https://doi.org/10.1530/EJE-07-0292
Savage, Martin O. ; Camacho-Hübner, Cecilia ; David, Alessia ; Metherell, Louise A. ; Hwa, Vivian ; Rosenfeld, Ronald (Ron) ; Clark, Adrian J L. / Idiopathic short stature : Will genetics influence the choice between GH and IGF-I therapy?. In: European Journal of Endocrinology. 2007 ; Vol. 157, No. SUPPL. 1.
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