Growth hormone deficiency causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Causes

Congenital growth hormone deficiency:

Genetic causes

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 GH-1:

• The POU1F1 gene is responsible for pituitary-specific transcription of genes for GH, prolactin, thyrotropin, and the growth hormone releasing hormone (GHRH) receptor [11,12]. PROP1 mutations result in failure to activate POU1F1/Pit1 gene expression and probably cause pituitary hypoplasia and/or familial multiple pituitary hormone deficiencies.
• Deletions and mutations of GH1 are the gene encoding GH, located on chromosome 17. Gene deletions, frameshift mutations, and nonsense mutations of GH1 have been described as causes of familial GHD.

Structural causes 

It is associated with midline craniofacial anomalies causing agenesis of the hypothalamic-pituitary stalk.

GHD is highly likely to be permanent in these patients:

• Optic nerve hypoplasia
• Agenesis of corpus callosum
• Septo-optic dysplasia
• Empty sella syndrome
• Holoprosencephaly
• Encephalocele
• Hydrocephalus
• Arachnoid cyst
• Midline facial defects
• Single central incisor

Acquired growth hormone deficiency

• GHD following brain surgery and radiation therapy for brain tumors. Permanent GHD is highly likely to be permanent in infants or young children.
• Central nervous system infection
• Tumors of hypothalamus or pituitary
• Pituitary adenoma
• Craniopharyngioma
• Rathke’s cleft cyst
• Glioma/astrocytoma
• Germinoma
• Infiltrative/granulomatous disease:
• Langerhans cell histiocytosis
• Sarcoidosis
• Tuberculosis
• Hypophysitis
• Cranial irradiation
• Surgery of the pituitary or hypothalamus
• Infarction
• Spontaneous
• Sheehan’s syndrome
• Idiopathic

Laron syndrome

• Growth hormone insensitivity is a reduction in or absence of the biological effects of growth hormone despite normal or above normal production and secretion of GH.
• These disorders are characterized by growth failure and normal or increased circulating levels of GH, in contrast with GH deficiency. 

• It is the most common known cause of genetically-mediated GHI.
• is characterized by severe postnatal growth failure.
• It is caused by homozygous or compounds heterozygous mutations in the growth hormone (GH) receptor gene; a variety of mutations have been identified, most of which affect the extracellular GH-binding region of the receptor.
• reflected by IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels.
• Adult height does not correlate with genotype or with measures of height in family members.
• hyperlipidemia and episodes of hypoglycemia Data are conflicting on the risk of insulin resistance.