Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4)
therapies represent a novel approach to
cancer treatment via disruption of immune tolerance to
antigens located on
tumor cells. Disruption of immune tolerance, however, may occur at a cost. A host of immune related adverse events (IRAEs) are associated with anti-CTLA-4
therapy.
Autoimmune hypophysitis has been reported in up to 17% of patients with
melanoma and
renal cell carcinoma treated with this
therapy. Familiarity with the spectrum of IRAEs connected to these
therapies is paramount for endocrinologists, oncologists and those involved in the care of these subjects. We review here key aspects of diagnosis and treatment of anti-CTLA-4 antibody
therapy resultant IRAEs. We describe the first two cases of
hypopituitarism in
prostate cancer subjects undergoing
experimental therapy with
ipilimumab. The clinical evidence strongly suggests that the
prostate cancer subjects developed
autoimmune hypophysitis as a consequence of anti-CTLA-4 treatment. High dose
glucocorticoid treatment resulted in markedly improved symptoms, and resolution of focal symptoms and
diabetes insipidus. One subject recovered pituitary-thyroid axis function after 9 months; however, both continue to require GC replacement. These cases highlight the importance of early screening and treatment for
hypopituitarism in all subjects undergoing treatment with anti-CTLA-4
therapy to prevent a potentially fatal outcome from secondary
adrenal insufficiency, a readily treatable disease. We recommend mandatory long term follow-up to monitor the development of other hormonal deficits.