Growth hormone deficiency causes

Causes of growth hormone deficiency could be congenital or acquired. Congenital causes can be genetic or structural. The genetic causes are due to genetic mutations in POU1F1, PROP-1, and GH-1 genes while the structural causes include optic nerve hypoplasia, agenesis of corpus callosum, septo-optic dysplasia, empty sella syndrome, and holoprosencephaly. Acquired causes of growth hormone deficiency include brain surgery and radiation therapy for brain tumors, central nervous system infection, craniopharyngioma, and pituitary adenoma.

It is usually recognized by the presence of affected relatives and confirmed by molecular testing for the causative genes, which include POU1F1, PROP-1, and GH1:

• The POU1F1 gene is responsible for pituitary-specific transcription of genes for GH, prolactin, thyrotropin, and the growth hormone-releasing hormone (GHRH) receptor.^[1]
• PROP1 mutations result in failure to activate POU1F1/Pit1 gene expression and probably cause pituitary hypoplasia and familial multiple pituitary hormone deficiencies.^[2]
• Gene deletions, frameshift mutations, and nonsense mutations of GH1 which codes for GH, have been described as causes of familial GHD.^[3][4]

• GHD is highly likely to be permanent in these patients
• It is associated with midline craniofacial anomalies causing agenesis of the hypothalamic-pituitary stalk:^[5]
  • Optic nerve hypoplasia
  • Midline facial defects
  • Agenesis of corpus callosum
  • Arachnoid cyst
  • Holoprosencephaly
  • Septo-optic dysplasia
  • Encephalocele
  • Empty Sella syndrome
  • Hydrocephalus

• GHD following brain surgery and radiation therapy for brain tumors. Permanent GHD is highly likely to be permanent in infants or young children^[6]
• Central nervous system infection^[5]
• Pituitary adenoma^[7]
• Craniopharyngioma
• Rathke’s cleft cyst
• Glioma/astrocytoma
• Germinoma
• Infiltrative/granulomatous disease:^[8]
  • Langerhans cell histiocytosis
  • Sarcoidosis^[9]
  • Tuberculosis
  • Hypophysitis^[10]
• Surgery of the pituitary or hypothalamus^[11]
• Sheehan’s syndrome^[12]
• Idiopathic

• This is the most common known cause of genetically-mediated growth hormone insensitivity (GHI).^[13]
• Growth hormone insensitivity is an absence of the effects of growth hormone despite a normal production of GH.
• Laron syndrome is characterized by growth failure and normal levels of GH.
• It is caused by mutations in the growth hormone receptor gene which affects the GH-binding of the receptor.
• Its severity correlates to IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels.

Haleigh Williams, B.S. Template:WS