Figure 5 – Proposed pathogenesis of anti-CTLA-4 antibody-induced hypophysitis. The CTLA-4 antibody binds to pituitary CTLA-4 antigen, inducing complement activation and infiltration with macrophages and other inflammatory cells, leading to phagocytosis and enhanced antigen presentation. Subsequently, autoimmune type IV hypersensitivity reactions start, with infiltration of the anterior pituitary by autoreactive T lymphocytes that eventually leads to pituitary cytotoxicity and inflammation. Moreover, patients with anti-CTLA-4 antibody-induced hypophysitis develop pituitary antibodies that predominantly recognize TSH- FSH- and ACTH-secreting cells.