Genetic causes and treatment of isolated growth hormone deficiency-an update

Nat Rev Endocrinol. 2010 Oct;6(10):562-76. doi: 10.1038/nrendo.2010.147.


Isolated growth hormone deficiency is the most common pituitary hormone deficiency and can result from congenital or acquired causes, although the majority of cases are idiopathic with no identifiable etiology. Known genes involved in the genetic etiology of isolated growth hormone deficiency include those that encode growth hormone (GH1), growth-hormone-releasing hormone receptor (GHRHR) and transcription factor SOX3. However, mutations are identified in a relatively small percentage of patients, which suggests that other, yet unidentified, genetic factors are involved. Among the known factors, heterozygous mutations in GH1 remain the most frequent cause of isolated growth hormone deficiency. The identification of mutations has clinical implications for the management of patients with this condition, as individuals with heterozygous GH1 mutations vary in phenotype and can, in some cases, develop additional pituitary hormone deficiencies. Lifelong follow-up of these patients is, therefore, recommended. Further studies in the genetic etiology of isolated growth hormone deficiency will help to elucidate mechanisms implicated in the control of growth and may influence future treatment options. Advances in pharmacogenomics will also optimize the treatment of isolated growth hormone deficiency and other conditions associated with short stature, for which recombinant human growth hormone is a licensed therapy.

Publication types

  • Review

MeSH terms

  • Dwarfism, Pituitary / genetics*
  • Human Growth Hormone / genetics*
  • Humans
  • Mutation
  • Receptors, Neuropeptide / genetics
  • Receptors, Pituitary Hormone-Regulating Hormone / genetics


  • Receptors, Neuropeptide
  • Receptors, Pituitary Hormone-Regulating Hormone
  • Human Growth Hormone
  • somatotropin releasing hormone receptor