Hypophysitis Induced by Monoclonal Antibodies to Cytotoxic T Lymphocyte Antigen 4: Challenges from a New Cause of a Rare Disease

Abstract

Learning Objectives: After completing this course, the reader will be able to: Identify symptoms of hypophysitis as an infrequent immune related side effect of ipilimumab and other anti-CTLA-4 monoclonal antibodies.Select the appropriate diagnostic and therapeutic work-up for patients suspected of having anti-CTLA-4 monoclonal-induced hypophysitis. CME This article is available for continuing medical education credit at CME.TheOncologist.com Specific human monoclonal antibodies antagonize cytotoxic T-lymphocyte antigen 4 (anti–CTLA-4 mAbs), a negative regulator of the immune system, inducing unrestrained T-cell activation. In patients with advanced or metastatic melanoma, one of these agents, ipilimumab, produced considerable disease control rates and, for the first time, a clear improvement in overall survival outcomes. However, accumulating clinical experience with anti–CTLA-4 mAbs identified a novel syndrome of autoimmune and autoinflammatory side effects, designated as “immune-related adverse events,” including mainly rash, colitis, and hepatitis. Autoimmune hypophysitis has emerged as a distinctive side effect induced by anti–CTLA-4 mAbs. This condition may be life threatening because of adrenal insufficiency if not promptly recognized, but it may easily be diagnosed and treated if clinically suspected. Hypopituitarism caused by these agents is rarely reversible and prolonged or life-long substitutive hormonal treatment is often required. The precise mechanism of injury to the pituitary triggered by anti–CTLA-4 mAbs is yet to be fully elucidated.