Growth Hormone Deficiency



  • Growth hormone deficiency (GHD) is a rare cause of growth failure due to a lack of growth hormone action caused by a defect in GH synthesis (insufficient hormone) or release.
  • GHD can be associated with other pituitary hormone deficiencies.


  • Prevalence in the United States is approximately 1:4,000.
  • Males are more commonly diagnosed than females.
  • Two peak ages of diagnosis:
    • Infancy (<1 year of age) usually because of associated hypoglycemia
    • Childhood at >4 years of age, usually because of poor linear growth

Risk Factors


  • The majority of cases are either isolated GH deficiency with no clear genetic cause or occur as the result of nonspecific hypothalamic/pituitary damage from etiologies including infection, inflammation, tumors and their treatment (especially radiation therapy).
  • Neuromigrational defects such as septo-optic-dysplasia (SOD) are also associated with hypopituitarism. They can be associated with genetic causes (e.g., HESX1, SOX2, SOX3, and OTX2 mutations for SOD); however, most are usually sporadic, not associated with genetic conditions.
  • Autosomal recessive and autosomal dominant forms occur with mutations in the GH gene (GH1) and in the GH-releasing hormone receptor (GHRHR) gene.
  • X-linked forms also occur and can be associated with immunodeficiency (e.g., BTK).


GH has a number of anabolic actions, but its principal one is increasing linear growth. This occurs both from direct GH action on the growth plate and indirectly via stimulation of hepatic and growth plate insulin-like growth factor 1 (IGF-I).


  • Idiopathic: probably the commonest diagnosis but only made after exclusion of conditions causing GH deficiency that require further management
  • Congenital
    • Congenital malformation of the pituitary can be associated with the following:
      • Holoprosencephaly
      • Septo-optic dysplasia
      • Midline defects: cleft lip, cleft palate, central maxillary incisor
      • Ectopic posterior pituitary, small anterior pituitary, and/or hypoplastic infundibulum
    • Genetic mutations
      • Familial multiple anterior pituitary hormone deficiency (e.g., HESX1, SOX2, SOX3, LHX3, LHX4, GHRHR, POU1F1, PROP1)
      • GH1 gene mutations (Type Ia, Ib, II, III)
  • Acquired idiopathic
    • CNS tumors: craniopharyngioma, germinoma, medulloblastoma, glioma, pinealoma
    • Pituitary or hypothalamic irradiation
    • Trauma: child abuse or closed head injury
    • Surgical resection/damage of pituitary gland/stalk
    • Birth injury/perinatal insult
    • Infection: viral encephalitis, bacterial or fungal infection, tuberculosis
    • Vascular: pituitary infarction or aneurysm
    • Infiltration affecting pituitary gland or sella turcica: histiocytosis, sarcoidosis
    • Hypophysitis

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