Description

• Insufficient production of growth hormone (GH) in adults or children caused by problems arising in the pituitary gland and/or hypothalamus
• GH is produced by somatotroph cells of the anterior pituitary gland, which is stimulated by growth hormone–releasing hormone (GHRH) and inhibited by somatostatin from the hypothalamus.
• GH, also called somatotropin, is a polypeptide hormone that stimulates growth and cell reproduction.
• Hypopituitarism is a deficiency in at least one pituitary hormone, including GH.
• Panhypopituitarism is a deficiency in all the hormones produced in the pituitary gland.
• System(s) affected: endocrine, musculoskeletal, cardiovascular, psychological
• Synonym(s) and keywords: hypopituitarism; familial short stature; short height; growth pattern; pituitary dwarfism; acquired GHD; isolated GHD; congenital GHD; panhypopituitarism

Epidemiology

Incidence

• Most common cause of GHD in children is idiopathic.
• Most common cause of GHD in adults is a pituitary adenoma or treatment of the adenoma with surgery or radiotherapy:
  • 76% of patients with GHD had a pituitary tumor.
  • 13% had an extrapituitary tumor.
  • 8% idiopathic cause
  • 1% had sarcoidosis.
  • 0.5% had Sheehan syndrome.

Prevalence

• In children, isolated GHD is reported to affect 1 in 4,000.
• Adult-onset idiopathic GHD is extremely rare.

Etiology and Pathophysiology

• GHD is caused by a genetic or acquired absence or decline in production of GH.
• Hypothalamus secretes GHRH, which stimulates the pituitary to secrete GH.
• Somatostatin is secreted by the hypothalamus to inhibit GH secretion.
• When GH pulses are secreted into the blood, then insulin-like growth factor (IGF)-1 is released from the liver.
• GHD may result from disruption of the GH axis—in the higher brain, the hypothalamus, or the pituitary gland (1)[C].
• Congenital
  • Genetic (see “Genetics”)
  • Structural brain defects
    • Agenesis of corpus callosum
    • Septo-optic dysplasia
    • Empty sella syndrome
    • Encephalocele
    • Hydrocephalus
    • Arachnoid cyst
  • Associated midline facial defects
    • Single central incisor
    • Cleft lip/palate
• Acquired
  • Trauma
  • CNS infection
  • Tumors of hypothalamus or pituitary
    • Pituitary adenoma
    • Craniopharyngioma
    • Rathke cleft cyst
    • Glioma/astrocytoma
    • Germinoma
    • Metastatic tumor
  • Infiltrative/granulomatous disease
    • Sarcoidosis
    • Tuberculosis
    • Langerhans cell histiocytosis
    • Hypophysitis
  • Cranial irradiation
  • Idiopathic
  • Pituitary infarction
  • Surgical
  • Hemochromatosis (rare)

Genetics
A variety of congenital genetic causes of GHD:

• Transcription factor defects (POU1F1/PIT-1, PROP-1, LHX3/4, HESX-1, SOX-3, and PITX-2)
• GHRH-receptor gene defects
• GH secretagogue (GHS) receptor gene defects
• GH receptor/postreceptor defects
• Prader-Willi syndrome
• Deletion and mutation of GH-1

Commonly Associated Conditions

• Pituitary adenoma (particularly macroadenoma)
• Sarcoidosis
• Sheehan syndrome