TY - JOUR
T1 - Hypophysitis induced by monoclonal antibodies to cytotoxic T lymphocyte antigen 4
T2 - Challenges from a new cause of a rare disease
AU - Torino, Francesco
AU - Barnabei, Agnese
AU - de Vecchis, Liana
AU - Salvatori, Roberto
AU - Corsello, Salvatore M.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Anti-CTLA-4 monoclonal antibodies
KW - Hypophysitis
KW - Ipilimumab
KW - Tremelimumab
UR - http://www.scopus.com/inward/record.url?scp=84860135451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860135451&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2011-0404
DO - 10.1634/theoncologist.2011-0404
M3 - Article
C2 - 22477725
AN - SCOPUS:84860135451
SN - 1083-7159
VL - 17
SP - 525
EP - 535
JO - Oncologist
JF - Oncologist
IS - 4
ER -