Hypophysitis: Presenting Characteristics and Outcomes of 146 Patients

Introduction: Hypophysitis, inflammation of the pituitary gland of unclear etiologies that often mimics the clinical and radiographic features of sellar mass lesions, requires unique attention and management.

Methods: Patients diagnosed with hypophysitis at Partners Healthcare hospitals from 1984–2015 were retrospectively reviewed for patient characteristics, presenting symptoms, radiography, pathology, treatment, and outcomes; as approved by the PHS IRB.

Results: Retrospective review identified 146 patients, diagnosed at a median age of 50.3 years (range 8.4–90.1), of which 56% were male. 51% of cases developed in association with anti-CTLA-4 (ipilimumab or tremelimumab) and/or anti-PD-1 (pembrolizumab or nivolumab) therapy for metastatic cancer (melanoma comprised 90%) a median of 70 days after initiating therapy (range 14–1080). 9% of patients had a previously diagnosed autoimmune disorder and 11% of female patients presented in association with pregnancy. 72% of cases presented with symptoms of sellar perturbance, including headache (50%), diabetes insipidus (17%), dysmenorrhea/amenorrhea (14%), and visual field deficits (9%). Common hypothalamic-pituitary-axis laboratory abnormalities at presentations included low cortisol (37%), low prolactin (35%), and low TSH (19%).

Incidental discovery was most often due to brain imaging for metastatic cancer. On MRI, the lesions spanned a median of 0.9 cm (range 0.2–2.3) and were often associated with sellar expansion (81%), infundibular thickening (48%), and pituitary midline shift (15%). There was concern for pituitary adenoma or other sellar tumor on imaging in up to 36% of cases, which underwent surgery (65% underwent biopsy-only). Pathology revealed lymphocytic (79%), granulomatous (11%), xanthogranulomatous (8%), and plasmacytic IgG4-related (2%) hypophysitis. 90% of cases were treated with high-dose steroids, including prednisone (70%, median 5 mg po daily) and hydrocortisone (30%, median 25 mg po daily).

Median follow-up time was 25 mos (range: 2–221). 73% of patients experienced complete symptomatic resolution by last follow-up, and 93% experienced at least partial improvement. Complete resolution of endocrinologic laboratory abnormalities was observed in 63% of cases. Complete radiographic resolution was observed in 76% of patients, with at least partial improvement in 93%. Treatment with steroids and checkpoint inhibitor therapy-associated hypophysitis were associated with improved rates of radiographic resolution. Hypophysitis with underlying autoimmune disorders demonstrated more limited improvement. Recurrence of hypophysitis occurred in 5% of cases, and 12% of those that underwent surgery.

Conclusions: Hypophysitis is a rare inflammatory condition of the pituitary gland of unclear etiology, notably associated with new checkpoint inhibitor therapies for cancer, autoimmune disorders, and pregnancy. Our radiographic, pathologic, and management findings are in line with those of previously published series. High-dose corticosteroids provide durable symptomatic and radiographic improvement.