Growth hormone insensitivity: Pathophysiology, diagnosis, clinical variation and future perspectives

The study of genetic growth hormone (GH) insensitivity is an evolving field . GH insensitivity syndrome (GHIS), otherwise known as Laron syndrome, is a heterogeneous disorder. Biochemical features consist of severe insulin-lik e growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) deficiency an d elevated GH secretion. In a heterogeneous 'European' cohort of GHIS patie nts, features varied from classical to moderate abnormalities of phenotype and endocrine disturbance. A study of facial features within this series sh owed that a mild subgroup existed with normal facies, mild short stature an d moderate biochemical abnormalities. Overlap with idiopathic short stature (ISS) exists, with heterozygous mutations of the GH receptor demonstrated to cause impaired growth. This 'partial' GHIS has not yet been defined endo crinologically. GH sensitivity, measured by IGR and IGFBP-3 responses in th e IGF-I generation test, may reveal abnormalities in ISS, although it is li kely that the dose of recombinant human GH and frequency of sampling in the test need to be modified. Copyright (C) 2001 S. Karger AG, Basel.