Table 3.

Hypophysitis due to combination therapy.

	Nivolumab (Nivo)	Ipilimumab (Ipi)	Combination therapy*
Incidence rate	0.3%–1.1%[8–11]	3.8%–5.6%[8–11]	7.7%–10.5%[8–12] OR 2.2%–3.5%[8,12] (vs monotherapy)
MRI	No change[13]	Enlargement of pituitary[13]	Variable
Hormone deficiency	Isolated ACTH deficiency[14]	Multiple anterior pituitary hormone deficiency[15–17]	Variable
mechanism	Autoimmune response against corticotrophs by ectopic ACTH expression in tumors[16]	Binding to CTLA-4 and activated classical pathway[19]	Unknown

ACTH = adrenocorticotropic hormone; CTLA-4 = cytotoxic T-lymphocyte associated antigen-4, MRI = magnetic resonance imaging, OR = odds ratio.

^*Combination of two immune checkpoint inhibitors, e.g. PD-1/PD-L1 plus CTLA-4 inhibitors.