What is hypophysitis?

From the Guidelines

Hypophysitis should be managed with hormone replacement therapy and high-dose corticosteroids as needed, with a focus on addressing deficiencies and preventing long-term sequelae, as recommended by the most recent guidelines from the American Society of Clinical Oncology 1.

Key Considerations

• Diagnosis requires a combination of clinical evaluation, hormone level testing, and MRI imaging showing pituitary enlargement with possible enhancement after contrast administration.
• Treatment depends on the underlying cause and severity, with mild cases potentially managed with observation and moderate to severe cases requiring hormone replacement therapy.
• Hormone replacement therapy typically includes hydrocortisone 15-25 mg daily in divided doses, levothyroxine 1.6 mcg/kg/day, sex hormones, and desmopressin 0.1-0.2 mg twice daily for diabetes insipidus if present.
• High-dose corticosteroids (prednisone 40-60 mg daily with gradual taper) may be used for autoimmune hypophysitis, with the goal of reducing inflammation and preventing long-term damage.
• Surgical intervention through transsphenoidal approach is reserved for cases with significant mass effect causing visual impairment or when diagnosis is uncertain.

Management by Grade

• Grade 1: Asymptomatic or mild symptoms, consider holding ICPi until patient is stabilized on replacement hormones, endocrine consultation, and corticosteroid replacement for adrenal insufficiency.
• Grade 2: Moderate symptoms, consider holding ICPi until patient is stabilized on replacement hormones, endocrine consultation, and clinic evaluation to assess need for steroids and volume repletion.
• Grade 3-4: Severe symptoms, hold ICPi until patient is stabilized on replacement hormones, endocrine consultation, and hospitalize or make an ED referral for normal saline, IV stress dose steroids, and taper stress dose corticosteroids down to oral maintenance doses over 5-7 days.

Additional Considerations

• All patients need education on stress dosing for sick days, use of emergency injectables, when to seek medical attention for impending adrenal crisis, and a medical alert bracelet or necklace for adrenal insufficiency.
• Endocrine consultation should be part of planning before surgery or high-stress treatments.
• Using hydrocortisone allows for recreation of the diurnal rhythm of cortisol, and typically 2/3 of the dose is given in the morning and 1/3 in the early afternoon.
• DHEA replacement is controversial but deficiency can be tested and replacement considered in women with low libido and/or energy who are judged to be otherwise well replaced, as noted in 1.

From the Research

Definition and Classification of Hypophysitis

• Hypophysitis is a broad term used to describe conditions leading to inflammation of the pituitary gland and the pituitary stalk 2.
• It may develop as a primary condition or secondary to other diseases 2.
• Hypophysitis is classified based on aetiological, anatomical, and histological criteria 2, 3.

Clinical Symptoms and Diagnosis

• Clinical symptoms result from enlargement of the pituitary gland, hormonal deficiencies, diabetes insipidus, and hyperprolactinemia 2.
• Histopathological verification of tissue samples from a pituitary biopsy remains the gold standard in diagnosing hypophysitis, but it is rarely performed due to its invasiveness and risk 2.
• The diagnosis is based mainly on clinical presentation, laboratory tests, and imaging 2, 4.
• Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity 3.

Treatment and Management

• The basic therapy relies on hormonal replacement 2.
• High doses of steroids are the first-line treatment of symptoms caused by mass effect in sella and compression of surrounding structures 2, 5.
• In steroid-resistant patients or in cases of unacceptable side effects, treatment with other immunosuppressant drugs was administered with success 2, 3.
• Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy 3, 4.

Epidemiology and Subtypes

• The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in the medical community, improvements in imaging techniques, and a rise in the occurrence of certain forms of hypophysitis such as IgG4 hypophysitis and immune checkpoint inhibitor induced hypophysitis 6.
• Primary autoimmune hypophysitis has stood out as the most relevant type of hypophysitis, but with the advent of immunotherapy for the treatment of malignancies and identification of hypophysitis as an immune-related adverse event, hypophysitis has garnered increasing interest and recognition 4.
• Idiopathic hypophysitis was the most common etiology in a case series of seven patients with hypophysitis 5.