• Generalized condition caused by deficiency of anterior pituitary hormones: adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin. Less commonly, the posterior pituitary gland’s hormones can be affected: vasopressin (AVP) (antidiuretic hormone [ADH]) and oxytocin (1)[A].
  • Generally, the order that hormone deficiencies develop is predictable, with decreased secretion of hormones least essential for life (GH, LH, and FSH) occurring earlier and more frequently than TSH and ACTH.
  • System(s) affected: cardiovascular, endocrine/metabolic, gastrointestinal, musculoskeletal, nervous, reproductive, skin/exocrine
  • Synonym(s): empty sella syndrome; Simmonds syndrome; panhypopituitarism; Sheehan syndrome (postpartum); pituitary apoplexy



  • 40 new cases per million per year
  • Adults and children. In children, it may cause short stature and pubertal delay.
  • Predominant sex: male = female


  • 46/100,000
  • 61% due to pituitary tumors, 9% parapituitary lesions, 19% other causes, 11% idiopathic

Etiology and Pathophysiology

  • Childhood
    • Genetic disorders
    • Perinatal asphyxia
    • Developmental disorders/pituitary hypoplasia, aplasia
    • Craniopharyngioma, other tumors
    • Cranial irradiation
    • Head trauma
  • Adult
    • Pituitary tumors: most common etiology; other intrasellar or parasellar tumors: meningiomas, gliomas, metastases, craniopharyngiomas, chordomas, ependymomas, suprasellar dysgerminomas, infundibulomas, astrocytomas, hamartomas
    • Surgery on pituitary or adjacent structures, cranial irradiation
    • Vascular: internal carotid artery aneurysm, subarachnoid hemorrhage, pituitary infarction, apoplexy, postpartum hemorrhage with hypotension (Sheehan syndrome)
    • Head trauma
    • Infection: abscess, hypophysitis, meningitis, encephalitis, tuberculosis, pneumocystic pneumonia, histoplasmosis, toxoplasmosis, aspergillosis, cytomegalovirus
    • Infiltrative conditions: hemochromatosis, granulomatous disease, histiocytosis X, sarcoidosis
    • Hypothalamic disease (secondary hypopituitarism)
    • Autoimmune disease: lymphocytic hypophysitis
    • Pituitary hemorrhage (apoplexy)
    • Empty sella


  • Pituitary and hypothalamic hormone transcription factor defects cause the following congenital hormone deficiencies:
    • AVP, diabetes insipidus
    • DAX-1, congenital adrenal hypoplasia, hypogonadotropic hypogonadism
    • GnRH-R and GPR54, loss-of-function mutations
    • HESX-1, associated with septo-optic dysplasia
    • KAL1 and FGFR1, Kallmann syndrome
    • PROP1, LHX3, LHX4, combined pituitary hormone deficiency
    • POMC, ACTH deficiency, obesity, red hair
    • POU1F1 (Pit-1), combined pituitary hormone deficiency
    • SF1, adrenal failure, 46,XY gonadal dysgenesis
    • OTX2, orthodenticle family located on chromosome 14q23.1
    • PITX2, associated with Rieger syndrome, which is characterized by anomalies of the anterior chamber of the eye in association with mental retardation, dental hypoplasia, and GHD
  • Genetic defects in pituitary hormone receptors
    • ACTH receptor defects: congenital insensitivity to ACTH
    • GH receptor defects: Laron dwarfism
    • LH/FSH receptor mutations
    • TSH receptor loss-of-function mutation

Risk Factors

  • Pituitary or parapituitary tumors
  • Pregnancy and delivery
  • Head trauma
  • Pituitary or cranial radiation
  • Pituitary surgery
  • Vascular aneurysms and cerebrovascular accidents
  • Lymphocytic hypophysitis
  • Infiltrative diseases
  • Infections

General Prevention

Prevention of head trauma, experienced neurosurgeon, early detection of pituitary tumors, improved obstetric care (2)[B]

Commonly Associated Conditions

  • Diabetes insipidus
  • Kallmann syndrome
  • Delayed puberty with growth delay

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