title: Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
abstract: Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4CD25 T cells. In patients with advanced melanoma, our group reported that administration of anti-CTLA-4 antibody mediated objective cancer regression in 13% of patients. This study also established that the blockade of CTLA-4 was associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and a single case of hypophysitis. Since this initial report, 7 additional patients with anti-CTLA-4 antibody-induced autoimmune hypophysitis have been accumulated. The characteristics, clinical course, laboratory values, radiographic findings, and treatment of these 8 patients are the focus of this report.
authors.affiliation: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1201, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Blansfield
authors.forename: Kimberly E
authors.initials: KE
authors.lastname: Beck
authors.forename: Khoi
authors.initials: K
authors.lastname: Tran
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Richard E
authors.initials: RE
authors.lastname: Royal
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.forename: Leah R
authors.initials: LR
authors.lastname: Haworth
authors.forename: Catherine
authors.initials: C
authors.lastname: Levy
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy; D060908:CTLA-4 Antigen; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010902:Pituitary Gland / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human