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Cytotoxic T-Lymphocyte-Associated Antigen-4 Blockage Can Induce Autoimmune Hypophysitis in Patients With Metastatic Melanoma and Renal Cancer

Blansfield, Joseph A; Beck, Kimberly E; Tran, Khoi; Yang, James C; Hughes, Marybeth S; Kammula, Udai S; Royal, Richard E; Topalian, Suzanne L; Haworth, Leah R; Levy, Catherine; Rosenberg, Steven A; Sherry, Richard M

doi: 10.1097/01.cji.0000178913.41256.06
Clinical Study

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4+CD25+ 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.

From the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Received for publication April 26, 2005; accepted July 11, 2005.

Reprints: Richard M. Sherry, Surgery Branch, National Cancer Institute, National Institutes of Health CRC, Room 3W-5942, 10 Center Drive, Bethesda, MD 20892-1201 (e-mail:

© 2005 Lippincott Williams & Wilkins, Inc.