Lymphocytic hypophysitis

Lymphocytic hypophysitis is a rare autoimmune disease characterised by inflammation of the pituitary gland and sometimes the pituitary stalk. It can occur in association with other autoimmune disorders, including immunoglobulin G4 (IgG4) disorders. It is often misdiagnosed as a pituitary adenoma. The typical presentation is headache and hypopituitarism, particularly diabetes insipidus and adrenocorticotrophic hormone (ACTH) deficiency (which can occur in isolation). Visual disturbance can also occur.

Lymphocytic hypophysitis is more common in pregnant women and the early postpartum period, although it can occur in women at any time, as well as men and children.

Immune checkpoint inhibitors (eg ipilimumab, tremelimumab, pembrolizumab, nivolumab, pidilizumab), which are used in cancer immunotherapy, can cause an autoimmune hypophysitis. Patients receiving immune checkpoint inhibitor therapy who present with headache, fatigue and hyponatraemia should be investigated for autoimmune hypophysitis with full biochemical assessment of pituitary function and pituitary magnetic resonance imaging (MRI).

Urgently refer any patient with suspected lymphocytic hypophysitis to an endocrinologist.

Evidence to guide the management of lymphocytic hypophysitis is limited. Management involves replacement for pituitary hormone deficiencies (see Hypopituitarism), and treatment for pressure effects (eg severe headache, optic chiasm compression or other cranial nerve palsies). Spontaneous resolution of pituitary enlargement and improved pituitary function have been reported in some patients receiving hormone replacement and symptomatic management only.

Treatment with high-dose glucocorticoids can reduce the inflammatory process. It is important to measure IgG4 concentration before starting glucocorticoid therapy. Relapse following initially successful glucocorticoid treatment can be treated with a repeat course. An alternative immunosuppressant drug, such as azathioprine, can be used instead of the repeat course of glucocorticoid treatment, or in combination with the repeat course. Stereotactic radiotherapy can also be beneficial following relapse or unsuccessful glucocorticoid therapy.

Surgery is indicated for patients with ongoing evidence of optic chiasm compression, or for histological confirmation of the diagnosis in patients with an unresponsive lesion.