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Endocrinological side-effects of immune checkpoint inhibitors

Torino, Francesco; Corsello, Salvatore M.; Salvatori, Roberto

doi: 10.1097/CCO.0000000000000293
SUPPORTIVE CARE: Edited by Jean A. Klastersky

Purpose of review Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance.

Recent findings Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent.

Summary In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

aDepartment of Systems Medicine, Chair of Medical Oncology, Tor Vergata University of Rome

bEndocrinology Unit, Catholic University of Sacred Heart, Rome, Italy

cDivision of Endocrinology and Metabolism and Pituitary Center, Johns Hopkins University, Baltimore, Maryland, USA

Correspondence to Roberto Salvatori, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University, 1830 East Monument Street, #333 Baltimore, MD 21287, USA. Tel: +1 410 955 3921; fax: +1 410 367 2042; e-mail:

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