Hypophysitis Associated with Immune Checkpoint Inhibitors

Hypophysitis is a well-known adverse event associated with ICIs, particularly with anti-CTLA-4 agents like ipilimumab. Its incidence is highest in patients receiving combination ICIs therapy (eg, ipilimumab-nivolumab). IRH typically presents with nonspecific symptoms that can be easily overlooked or erroneously attributed to cancer itself or cancer-related comorbidities or treatments. Secondary adrenal insufficiency is the most significant endocrine alteration. It is typically isolated in patients receiving anti-PD-(L)1 therapy. Other hormonal deficiencies, including TSH and gonadotropin deficiencies are more frequent with anti-CTLA-4 therapy. In contrast, posterior pituitary involvement and AVP-D are rare, and should raise suspicion for an alternative diagnosis such as pituitary metastasis, warranting imaging studies. Mass effects symptoms and MRI findings are rare compared to primary autoimmune hypophysitis. Treatment is based on hormone replacement therapy with adrenal insufficiency generally requiring long-term glucocorticoid replacement therapy since recovery of HPA axis function is uncommon. High-dose glucocorticoids and ICIs discontinuation are generally not needed and reserved for patients with significant mass effect symptoms or severe adverse events.