title: Growth hormone insensitivity: pathophysiology, diagnosis, clinical variation and future perspectives.
abstract: 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-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) deficiency and elevated GH secretion. In a heterogeneous 'European' cohort of GHIS patients, features varied from classical to moderate abnormalities of phenotype and endocrine disturbance. A study of facial features within this series showed that a mild subgroup existed with normal facies, mild short stature and 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 endocrinologically. GH sensitivity, measured by IGF-I and IGFBP-3 responses in the IGF-I generation test, may reveal abnormalities in ISS, although it is likely that the dose of recombinant human GH and frequency of sampling in the test need to be modified.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, and The Royal London School of Medicine and Dentistry, UK. m.o.savage@mds.qmw.ac.uk
authors.forename: M O
authors.initials: MO
authors.lastname: Savage
authors.forename: C P
authors.initials: CP
authors.lastname: Burren
authors.forename: J C
authors.initials: JC
authors.lastname: Blair
authors.forename: K A
authors.initials: KA
authors.lastname: Woods
authors.forename: L
authors.initials: L
authors.lastname: Metherell
authors.forename: A J
authors.initials: AJ
authors.lastname: Clark
authors.forename: C
authors.initials: C
authors.lastname: Camacho-Hübner
mesh_terms: D001827:Body Height / Q000502:physiology; D004351:Drug Resistance; D014644:Genetic Variation; D006130:Growth Disorders / Q000209:etiology; D019382:Human Growth Hormone / Q000502:physiology*; D006801:Humans; D013577:Syndrome
chemical_list: D019382:Human Growth Hormone