This systematic review delineates the distinct clinical, radiological, and therapeutic profiles of immune checkpoint inhibitor (ICPi)-associated hypophysitis across CTLA-4 inhibitor monotherapy, PD-1/PD-L1 inhibitor monotherapy, and combination ICPi regimens.CTLA-4 inhibitors, particularly ipilimumab, are linked to earlier onset and multifaceted hypopituitarism with more frequent MRI abnormalities, while PD-1/PD-L1 inhibitors typically cause delayed, isolated ACTH deficiency with variable imaging findings. The gene discussed is CD274; the disease is hypopituitarism.