Lymphocytic (Autoimmune) Hypophysitis

Description

• A rare autoimmune disease that occurs when the pituitary gland is infiltrated with lymphocytes and plasma cells, leading to impaired hormonal secretion
• Patients present with varying degrees of pituitary hormonal impairment or enlargement.
• Cause is usually unknown.
• The most common form affects the anterior pituitary and causes hypopituitarism.
• Less commonly affects the infundibulum or posterior pituitary, causing diabetes insipidus and hyperprolactinemia

Epidemiology

• Predominantly seen in women: female > male (5:1)
• Strong association with pregnancy, most frequently occurring in the gestational or postpartum period, but cases outside of pregnancy are increasingly seen
• Females tend to present at a younger age (35 years) than do males (45 years).

Incidence

• Annual incidence estimated at 1 case per 9 million
• Increasingly becoming more recognized
• Thought to be underestimated because of the following:
  • Frequency of case reports are increasing.
  • Undiagnosed cases due to indolent disease

Prevalence

• Uncommon
• Found in <1% of all surgical pituitary samples

Etiology and Pathophysiology

• Most commonly caused by an autoimmune infiltration that includes an admixture of T and B lymphocytes with plasma cells
  • Causes extrasellar pituitary enlargement
  • CD8 T cells mediate the attack on pituitary cells.
  • Antipituitary antibodies are considered markers of the T-cell mediation and are detectable in serum.
  • It is unknown if antipituitary antibodies play a pathogenic role.
• Can also be caused by an inflammatory process
  • Initially leads to symptoms consistent with a pituitary mass effect (similar to pituitary adenoma)
  • Followed by fibrosis and shrinkage, causing differing degrees of hypopituitarism
  • Extension of the inflammatory process into the posterior pituitary and up into the neurohypophysis leads to diabetes insipidus, which is more common in males.
  • With complete progression, panhypopituitarism occurs with an empty sella turcica.
• Autoimmune
• Inflammatory

Genetics

• Patients often have family history of autoimmunity.
• HLA DR4 allele, HLA DR5 allele (DR4 > DR5)
• Recent association found with HLA DQ8 and DR53 alleles as well
• Can be associated with antibody to PIT1 (POU1F1)

Risk Factors

• Female gender
• Pregnancy
• Pregnant type 1 diabetics are at even higher risk.
• Personal or family history of autoimmune disease
• May be associated with viral infections, particularly meningoencephalitis
• CTLA-4 antibody cancer treatment (e.g., ipilimumab or tremelimumab)

General Prevention

None

Commonly Associated Conditions

• Aseptic meningitis: unknown if simple association or causal
• Other autoimmune polyendocrinopathies are the following:
  • Hashimoto thyroiditis; Graves disease is most common.
  • Addison disease, type 1 diabetes mellitus, central diabetes insipidus, chronic atrophic gastritis, polyglandular autoimmune disease type 1 and type 3, systemic lupus erythematosus, Sjögren syndrome, autoimmune hepatitis, pernicious anemia, and primary biliary cirrhosis