title: Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4: challenges from a new cause of a rare disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Torino
authors.forename: Agnese
authors.initials: A
authors.lastname: Barnabei
authors.forename: Liana
authors.initials: L
authors.lastname: De Vecchis
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.forename: Salvatore M
authors.initials: SM
authors.lastname: Corsello
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology; D010900:Pituitary Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D035583:Rare Diseases / Q000139:chemically induced* / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab