Autoimmune hypophysitis

Signs and symptoms

Autoimmune hypophysitis can cause shortages of one or more pituitary hormones. When the posterior pituitary is affected, central diabetes insipidus may result; damage to the anterior pituitary can lead to central adrenal insufficiency and central hypothyroidism. Symptoms vary based on which part of the gland is involved. Lymphocytic adenohypophysitis (LAH) targets anterior pituitary cells, sometimes producing no symptoms, or causing adrenal insufficiency, hypothyroidism, or hypogonadism depending on which cells are harmed.

Inflammation may block dopamine from the hypothalamus, raising prolactin levels and occasionally triggering milk production in older girls and women. Lymphocytic Infundibuloneurohypophysitis (LINH) affects the posterior pituitary, causing diabetes insipidus. Both types can also cause headache or bitemporal hemianopia due to mass effect. Common complaints include nausea, vomiting, fatigue, loss of libido, amenorrhea, and dizziness.

Autoimmune destruction typically takes 12 to 40 years to show symptoms, though isolated attacks from drug reactions or unknown causes may resolve after about a year of immune suppression. Faster progression is typical during or shortly after pregnancy, including after miscarriage or abortion.

Diagnosis

Diagnosing lymphocytic hypophysitis often requires ruling out other conditions first, and a tissue biopsy remains the only way to confirm it. While no specific autoantigen has been identified, doctors rely on symptoms of pituitary hormone deficiency, lab tests, and imaging to guide them. Hormone tests can be costly and tricky to interpret, as levels fluctuate throughout the day and with metabolic changes.

A blood test for antibodies to a 49,000 molecular weight pituitary protein may signal an immune process, but biopsy is still needed for certainty. A full workup for other autoimmune disorders should include a complete blood count, metabolic panel, C-reactive protein, erythrocyte sedimentation rate, antinuclear antibody, and lupus antibodies. Gadolinium-enhanced MRI is the preferred imaging method, mainly to distinguish this condition from a pituitary adenoma.

Treatment

For most patients, a course of glucocorticoids over several months will calm the inflammation. If symptoms return or steroids don't work, doctors may turn to immunosuppressants like methotrexate, azathioprine, or cyclosporine.

A combination of azathioprine and glucocorticoids has proven effective for recurrent cases. When high prolactin levels stem from pituitary inflammation, dopamine agonists like cabergoline or bromocriptine can be used. Surgery is reserved for those with vision issues, eye movement problems, significant compression, or when a tissue diagnosis is needed.

Epidemiology

A large-scale Swedish cadaver study indicated that perhaps as much as 5% of the population experiences some amount of autoimmune pituitary destruction, with perhaps half that many showing clinical manifestations. The prevalence of all types of hypophysitis is low, with an incidence of approximately 1 in 9 million, though this may be an underestimate, especially due to recent use of immune checkpoint inhibitors for cancer treatments. Although cases occur in children and the elderly, the mean age of diagnosis for men is 44.7 years and for women is 34 years.

Did You Know?

• Autoimmune attack of the pituitary gland was first discovered as a result of an autopsy in 1962.
• As magnetic resonance imaging became more available, diagnosis increased dramatically.