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- Title
Idiopathic short stature: will genetics influence the choice between GH and IGF-I therapy?
- Authors
Savage, Martin O.; Camacho-Hübner, Cecilia; David, Alessia; Metherell, Louise A.; Hwa, Vivian; Rosenfeld, Ron G.; Clark, Adrian J. L.
- 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 GHor IGF-I therapy inISS is reviewed. Many ISS patientshave lowIGFI, 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 awide variability of phenotype in patients carrying identical mutations. HeterozygousGHreceptor (GHR)mutationswere 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 GHor IGF-I therapy. Endocrine abnormalities have closer correlationswith phenotype and may thus be a better guide to therapeutic responsiveness.
- Subjects
SHORT stature; SOMATOMEDIN; SOMATOTROPIN; GENETIC mutation; PHENOTYPES; ENDOCRINE diseases; GROWTH disorders
- Publication
European Journal of Endocrinology, 2007, Vol 157, pS33
- ISSN
0804-4643
- Publication type
Article
- DOI
10.1530/EJE-07-0292