Empty Sella Syndrome



  • Normally, the pituitary gland sits in a small skull compartment at the base of the brain known as the sella turcica (Latin for “Turkish saddle”).
  • In empty sella syndrome (ESS), there is herniation of the suprasellar subarachnoid space into the sella turcica, which acts as a mass, resulting in compression of the pituitary gland. In effect, the pituitary gland appears flattened.
  • Synonym(s): intrasellar arachnoidocele
  • In ESS, the empty sella is not actually “empty”; it only appears to be on imaging. It actually contains the pituitary gland, pituitary stalk, arachnoid, CSF, and sometimes the optic system and 3rd ventricle.
  • Primary empty sella (PES)
    • Characterized by a congenital defect of the sellar diaphragm, either a tear or complete absence of the diaphragm, allowing herniation of CSF-filled arachnoid into the sella
    • The exact role that the defect plays is not currently known. Whether its presence alone is adequate to cause PES, is a predisposing factor, or is part of a larger and undiagnosed disease process has yet to be resolved.
    • Although there exists research claiming deficiencies of one or more pituitary hormones in PES (1), the evidence is inconsistent, raising the question of whether or not an “ESS” truly exists. Associated with the following:
      • Female sex
      • Obesity
      • Multiparity
      • Intracranial hypertension in 50% of cases
  • Secondary empty sella (SES)
    • Results from physical destruction of the pituitary gland either from iatrogenic or noniatrogenic causes
  • SES is more likely than PES to produce loss of pituitary functions, with consequent infertility and fatigue. In children:
    • Is much less common and usually less likely to be benign than in adults
    • Visual disturbances are seen more frequently than in adults.
    • More likely to result in pituitary insufficiency than in adults



  • ESS
    • Is seen in 5.5–35% of autopsies
    • Occurs at any age, in either sex. Women are generally affected more often than men with a ratio of 5:1 (PES) and increasing incidence with age.
    • Most commonly found in obese, multiparous women with hypertension
  • PES
    • Clinically evident endocrine disturbance is rare in PES; however, some studies report abnormal pituitary function tests in as high as 30–50% of patients who were studied.
    • Most common reported abnormalities are as follows:
      • Growth hormone (GH) deficiency
      • Hyperprolactinemia

Etiology and Pathophysiology

Several proposed mechanisms

  • PES
    • Incomplete formation of the sellar diaphragm overlying the pituitary. With pulsatile CSF flow and greater leakage into the sella, intrasellar pressure increases. As a result, the pituitary gland becomes compressed or appears to become compressed due to sellar expansion.
    • Obesity tends to cause a hypercapnic state, which causes increased CSF pressure. This may lead to sellar expansion.
    • Enlargement and subsequent involution of the pituitary gland during pregnancy has been proposed to contribute to ESS in multiparity.
  • SES
    • Iatrogenic causes include intracranial surgeries (especially transsphenoidal) and radiation treatment. Noniatrogenic causes include hemorrhage, infection, trauma, autoimmune conditions, or infarction of adenoma.

ESS is not typically inherited.

Risk Factors

  • History of intracranial surgery or brain radiation
  • Traumatic brain injury
  • Autoimmune disease
  • Infection (meningitis and encephalitis)
  • History of Sheehan syndrome (postpartum hypopituitarism), more common in multiple pregnancies
  • Obesity, severe GH deficiency (2)
  • History of pseudotumor cerebri

Commonly Associated Conditions

  • Benign intracranial hypertension (BIH)
  • Obesity
  • Pseudotumor cerebri
  • Hypertension
  • Diabetes mellitus
  • Autoimmune hypophysitis: There have been case reports where it was noted that patients would eventually develop ESS after autoimmune hypophysitis (3).
  • Early menopause (nearly 10% of females with ESS)
  • Sheehan syndrome
  • Rare lysosomal storage disease (Fabry disease) (4) and Erdheim-Chester syndrome
  • Multiple pregnancies

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