Introduction:
Hypophysitis caused by
immune checkpoint inhibitors (ICIs) has risen to the medical attention during the past decade. ICIs are
monoclonal antibodies that block the interaction between molecules that normally inhibit the function of effector T cells, ultimately increasing their ability to destroy
cancer cells but also causing immune-related adverse events, such as
hypophysitis.
Ipilimumab, a CTLA-4 blocker, was the first ICI approved from the Food and Drug Administration for advanced
melanoma patients in 2011. Several additional ICIs targeting CTLA-4, PD-1, or PD-L1 are now used in many clinical trials, making it important for physicians to recognize and treat
hypophysitis adequately.Areas covered: This review will provide insights into the mechanisms of pituitary toxicity, highlight the complexity of clinical phenotypes of ICI
hypophysitis, and offer practical recommendations.Expert opinion: ICI
hypophysitis differs in many respects from primary
hypophysitis, and also according to the type of ICI that caused it. Its pathogenesis remains unknown, although the expression of CTLA-4 and PD-1 on pituitary cells could play a role. The diagnosis is mainly clinical since there are no specific serological markers and MRI findings are subtle. The treatment is based on long-term
hormone replacement and does not typically require discontinuation of
immunotherapy.