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Cancer Treat Rev. 2017 Jul;58:70-76. doi: 10.1016/j.ctrv.2017.06.002. Epub 2017 Jun 22.

Endocrine-related adverse events associated with immune checkpoint blockade and expert insights on their management.

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Yale University School of Medicine and Yale Cancer Center, New Haven, CT, USA. Electronic address:
Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Yale School of Nursing, West Haven, CT, USA.
New York University, New York, NY, USA.
Fox Chase Cancer Center, Temple Health, Philadelphia, PA, USA.
University of New Mexico, Albuquerque, NM, USA.
Gustave Roussy and Paris-Sud University, Villejuif, France.


Agents that modulate immune checkpoint proteins, such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1), have become a mainstay in cancer treatment. The clinical benefit afforded by immune checkpoint inhibitors can be accompanied by immune-related adverse events (irAE) that affect the skin, gastrointestinal tract, liver, and endocrine system. The types of irAEs associated with immune checkpoint inhibitors are generally consistent across tumor types. Immune-related endocrine events can affect the pituitary, thyroid, and adrenal glands, as well as other downstream target organs. These events are unique when compared with other irAEs because the manifestations are often irreversible. Immune-related endocrine events are typically grade 1/2 in severity and often present with non-specific symptoms, making them difficult to diagnose. The mechanisms underlying immune-related target organ damage in select individuals remain mostly undefined. Management includes close patient monitoring, appropriate laboratory testing for endocrine function, replacement of hormones, and consultation with an endocrinologist when appropriate. An awareness of the symptoms and management of immune-related endocrine events may aid in the safe and appropriate use of immune checkpoint inhibitors in clinical practice.


Hypophysitis; Immune-related adverse events; Ipilimumab; Melanoma; Nivolumab; Thyroiditis

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