Diagnosis and Treatment of Hypophysitis

Diagnostic Criteria

The diagnosis of hypophysitis requires a combination of pituitary hormonal deficiencies (especially TSH or ACTH), characteristic findings on magnetic resonance imaging, and exclusion of other sellar pathologies, as recommended by the American College of Endocrinology 1
The presence of at least one pituitary hormonal deficiency (deficiency of TSH or ACTH required) combined with abnormality on magnetic resonance imaging, or at least two pituitary hormonal deficiencies (deficiency of TSH or ACTH required) in the presence of headache and other symptoms, is necessary for a confirmatory diagnosis, according to the Endocrine Society 1

Visual disturbances due to mass effect are a common presenting symptom, as reported by the Annals of Oncology 2
Diabetes insipidus is a less common symptom, occurring in approximately 7% of cases, as noted by the American College of Endocrinology 1

Initial hormonal evaluation should include cortisol, ACTH, TSH, T4, LH, FSH, estradiol (in premenopausal women), testosterone (in men), IGF-1, and prolactin, as recommended by the Annals of Oncology 2
Cortisol levels should be obtained at 9 AM (or randomly if the patient is unstable and treatment cannot be delayed), as suggested by the Annals of Oncology 2

The management of hypophysitis is based on physiological hormone replacement as the cornerstone, not high-dose steroids, which are only used for severe neurological symptoms due to mass effect, as stated by the American College of Endocrinology 3
Hydrocortisone 20/10 mg should be initiated if the morning cortisol level is low, and cortisol replacement should always be started at least 1 week before initiating T4 to prevent adrenal crisis, as recommended by the Annals of Oncology 2 and the American College of Endocrinology 3
Levothyroxine 50-100 mcg/day should be initiated after ensuring adequate cortisol replacement, and TSH and free T4 should be monitored every 1-2 weeks initially, as suggested by the Annals of Oncology 2

Surgery should be limited to specific cases, such as severe compressive symptoms and/or progressive deterioration, or lack of response to medical treatment with progressive visual deterioration, as noted by the World of Neurosurgery 4
The standard transnasal approach is the preferred surgical route, as recommended by the World of Neurosurgery 4

Rituximab is the most commonly used immunosuppressant, with a successful response in approximately two-thirds of patients, as reported by the World of Neurosurgery 4
Other immunosuppressive therapies, such as azathioprine, methotrexate, cyclosporine A, and mycophenolate, may be considered when glucocorticoids and/or surgery fail, as noted by the World of Neurosurgery 4

All patients with adrenal insufficiency should obtain and wear a medical alert bracelet, receive education on "sick day" rules, and have a prescription for emergency steroid use, as recommended by the American College of Endocrinology 3

The incidence of hypophysitis is higher with combination anti-PD(L)1/anti-CTLA-4 therapy (9-10%), followed by anti-CTLA-4 (2-6%) and anti-PD-1 (1%) therapy, as reported by the Annals of Oncology 2
Lymphocytic hypophysitis primarily affects pregnant women and is the most common histological subtype, as noted by the World of Neurosurgery 4
IgG4-related hypophysitis occurs frequently in men and is associated with systemic IgG4 disease, as reported by the World of Neurosurgery 4

Headache is reported in roughly 85 % of individuals with lymphocytic hypophysitis, making its absence a strong negative predictor for this condition. 5

The majority of patients at diagnosis show pituitary MRI abnormalities (e.g., gland enlargement, stalk thickening, suprasellar convexity, heterogeneous enhancement). Diagnosis requires either ≥ 1 pituitary hormone deficiency + MRI abnormality, or ≥ 2 hormone deficiencies. 5