-Review-

Immune Checkpoint Inhibitors and Associated Pituitary Dysfunctions: A Mini-Review

Izumi Fukuda

Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan

Immune checkpoint inhibitors (ICIs) are widely used for various types of advanced cancers. Currently, three types of ICIs are clinically available, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and antibodies targeting the programmed cell death protein-1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1). Although ICIs have improved the survival rates of several types of cancers, they induce immune-related adverse events (irAE) by their enhancement of immune responses. The pituitary gland is one of the common targets of irAE. In general, different clinical presentations of autoimmune pituitary dysfunctions are observed between anti-CTLA-4 and anti-PD-1/anti-PD-L1 antibodies, with anti-CTLA-4 inducing hypophysitis with multiple pituitary hormone deficiencies and targeting the PD-1/PD-L1 axis inducing isolated adrenocorticotropic hormone deficiency.
This review describes the current understanding of the pathophysiology, clinical manifestation, and management of hypophysitis caused by ICIs.

J Nippon Med Sch 2023; 90: 149-156

Keywords
hypophysis, isolated ACTH deficiency, immune checkpoint inhibitors

Correspondence to
Izumi Fukuda, MD, PhD, Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
i-fukuda@nms.ac.jp

Received, November 6, 2022
Accepted, December 28, 2022