Abnormalities of growth hormone action

Introduction 444 The growth hormone receptor and its signaling 444 Epidemiology of growth hormone insensitivity syndrome 446 Growth hormone insensitivity syndrome secondary to defects of its receptor 447 Growth hormone insensitivity secondary to defects in genes other than the growth hormone receptor 451 ‘Partial’ growth hormone insensitivity 453 Growth hormone insensitivity with normal levels of IGF-I: Defects beyond the IGF-I gene 454 Conclusion 455 Key learning points 455 References 455 Over the past 20 years, it has become recognized increasingly that poor growth may be caused not only by defects in growth hormone (GH) secretion, but also by defects in GH action, or GH insensitivity (GHI). The first description of GHI was by Laron and colleagues in 1966, who reported ‘three siblings with hypoglycemia and other clinical and laboratory signs of GH deficiency, but with abnormally high concentrations of immunoreactive serum GH’.1 The underlying cause of this condition, known as GHI syndrome (GHIS) or Laron syndrome, was not determined until 1989, however, when Godowski and co-workers cloned the human GH receptor gene and identified a partial GH gene deletion in three such patients.2 A wide range of GH receptor gene mutations and deletions have now been identified in GHIS subjects.