Hypophysitis: Evaluation and Management

Abstract

Hypophysitis is the acute or chronic inflammation of the pituitary gland. The spectrum of hypophysitis has expanded in recent years with the addition of two histologic subtypes and recognition as a complication of treatment with immune checkpoint inhibitors. Despite the increased number of published cases, the pathogenesis of hypophysitis is poorly understood, and treatment strategies are diverse and controversial. The diagnosis of hypophysitis generally requires histopathologic confirmation. The presentation and clinical course of hypophysitis varies. Hypophysitis can resolve spontaneously, relapse may occur, and some cases can be refractory to treatment.

High‐dose glucocorticoids for the treatment of ipilimumab‐induced hypophysitis is associated with reduced survival in patients with melanoma

“…[1][2][3][4][5] The incidence of hypophysitis after treatment with anticytotoxic T-lymphocyte antigen-4 (CTLA-4) therapy may approach 12%, although it is rare with agents targeting programmed cell death 1 (PD-1) and programmed death-ligand 1 (PD-L1). 9 Defects in the immune response are associated with primary and acquired resistance to CPIs. It is unclear whether higher doses of immunosuppressive medications affect patient outcomes in primary or CPI-associated hypophysitis, whether for endocrinologic endpoints or oncologic outcomes such as survival.…”

Primary Granulomatous Hypophysitis Presenting with Secondary Hypothyroidism

“…Central diabetes insipidus is also common. Our patient had complaints of sweating, insomnia, heat intolerance due to undetectable FSH and estradiol, and weight loss, fatigue, and presyncope from secondary adrenal insufficiency given her low morning cortisol (5,7). Radiographic imaging with MRI aids in diagnosis because it reveals the pituitary mass.…”

“…Mixed histology can be seen, however. Necrotizing hypophysitis has also been suggested as an additional variant, but only three cases have been reported in the literature (4,5).…”

“…It causes pituitary enlargement that mimics a macroadenoma (6). Secondary GH can be due to an infection, systemic inflammatory disorders such as sarcoidosis, Wegener granulomatosis, Crohn disease, Takayasu arteritis, Cogan syndrome, or a side effect of some medications, mostly in those receiving immunotherapy for metastatic melanoma with anti-CTLA4 and anti-PDi antibodies (3,5,8). Our patient's rheumatology evaluations, including DNA antibody, SSA/SSB antibodies, anti-Smith/RNP antibody, JO-1 antibody, anti-nuclear antibody, and rheumatoid factor, were within normal limits.…”

“…However long-term use of high-dose steroids is not desirable and can be detrimental to patients, given unwanted side effects. Other immunosuppressive agents such as methotrexate, azathioprine, rituximab, infliximab, cyclosporine, and mycophenolate mofetil have been utilized in a small number of patients with hypophysitis with some success (5,9).…”