The term growth hormone insensitivity describes a group of disorders, both inherited and acquired, in which there are clinical and endocrine features of insulin-like growth factor I (IGF-I) deficiency and resistance to exogenous human growth hormone, associated with growth hormone secretion that would not be considered abnormally low.1 2 In childhood, the principal result of growth hormone insensitivity is the failure of postnatal growth, leading, if untreated, to adult short stature. This group of disorders classified as growth hormone insensitivity however is becoming larger and more heterogeneous, as diagnostic methods improve and molecular analysis is applied to a wider range of patients with short stature.

The original description of growth hormone insensitivity3was of a genetic dysmorphic syndrome (Laron syndrome) characterised by extreme short stature, spontaneous hypoglycaemia, abnormal craniofacial development, microphallus in boys, and final adult height of 120–130 cm (less than −5 SDS (standard deviation score)). Several series of patients, mostly originating in consanguineous populations of Middle Eastern origin, have since been described.4-7Biochemical features in this classic form of growth hormone insensitivity consist of raised growth hormone secretion contrasting with low concentrations of serum IGF-I and IGF binding protein 3 (IGFBP-3).1 8 The primary defect in Laron syndrome was demonstrated to be at the level of the growth hormone receptor (GHR), with failure of growth hormone binding to hepatocytes,9and lack of a mitogenic response to growth hormone in T lymphocytes …