Fourth, onset time of major endocrine ADRs (ICI-DM, adrenal insufficiency, hypophysitis/hypopituitarism, and thyroid dysfunction) differed between different ICI therapies, typically within 12 weeks in anti-CTLA-4 monotherapy but diffusely ranging from 0 to 48 weeks in anti-PD-1 monotherapy. The gene discussed is CTLA4; the disease is Adrenal insufficiency.