hypophysitis

Last edited 11/2019

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement (1,2,3)

• pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or
  
  
• secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies)

Caturegli et al. reviewed the disease, showed that lymphocytic hypophysitis is classified into three forms, lymphocytic adenohypophysitis (LAH), lymphocytic infundibulo-neurohypophysitis (LINH), and lymphocytic panhypophysitis (LPH) (2)

• adenohypophysitis mainly affects the anterior pituitary
• infundibulo-neurohypophysitis involves the posterior pituitary and stalk
• panhypophysitis may be heterogeneous, and the pathogenesis includes local inflammation from the anterior pituitary, posterior pituitary, or pathological conditions of hypothalamic-pituitary region such as Rathke's cyst, craniopharyngioma, or germinoma

Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis (1,4)

Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement (4)

Clinical features:

• hypophysitis-related symptoms are:
  • headache, disturbances in visual acuity and the visual field, and hypopituitarism due to inflammation and compression of surrounding tissues by the enlarged pituitary
    • adrenocorticotropic hormone (ACTH) secretion is impaired first in most cases of hypophysitis (3)
    • increased prolactin (PRL) levels are observed, resulting in decreased luteinizing hormone/follicle stimulating hormone
    • hypogonadism also occurs by damage of gonadotrophs due to inflammation

Immunological insights:

• anti-Rabphilin antibody has been proposed to be a biomarker for lymphocytic infundibulo-neurohypophysitis

• immunological disorders such as anti-Pit-1 antibody syndrome are similar to the pathogenesis of lymphocytic hypophysitis - congenital combined TSH, GH, and PRL deficiency due to a Pit-1 gene mutation is a well-known cause of short stature

• immune checkpoint blockade such ipilimumab has been shown to induce anti-CTLA-4-related hypophysitis

Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy

• glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice (4)

Reference:

• Lin HH et al. In situ activation of pituitary-infiltrating T lymphocytes in autoimmune hypophysitis. Sci Rep 2017; 7: 43492.
• Caturegli P et al. Autoimmune hypophysitis. Endocr Rev 2005; 26: 599-614.
• Hashimoto K, Takao T, Makino S: Lymphocytic adenohypophysitis and lymphocytic infundibuloneurohypophysitis. Endocr J 1997; 44: 1-10.
• Joshi MN et al.MECHANISMS IN ENDOCRINOLOGY: Hypophysitis: diagnosis and treatment. Eur J Endocrinol. 2018 Sep;179(3):R151-R163