Hypothalamic-pituitary-adrenal axis dysfunction induced by cancer therapy with immune checkpoint inhibitors

Objective: to summarize current data on immune checkpoint inhibitor-induced hypothalamic-pituitary-adrenal axis dysfunction, with an emphasis on hypophysitis and primary adrenal insufficiency.

Material and Methods. A review of publications on endocrine immune-related adverse events from anti-CTLA-4, anti-PD-1 and antiPD-L1 inhibitors was carried out from January 2015 to October 2025 using Pubmed, Cochrane library, Google Scholar, and Elibrary systems. Of the 876 studies found, 45 were used to write the systematic review.

Results. immune checkpoint inhibitor-induced hypothalamic-pituitary-adrenal axis dysfunction is a serious immune-related adverse event. It commonly presents as hypophysitis (particularly with anti-CTLA-4, causing pituitary deficiency) and primary adrenal insufficiency (risking fatal Addisonian crisis). Diagnosis is complicated by the nonspecific clinical presentation. Essential evaluation includes assessing symptoms, adrenocorticotropic hormone, cortisol, electrolyte levels, and hormones of other axes, as well as magnetic resonance imaging of the pituitary gland and computed tomography of the adrenal glands. in most cases, long-term, and sometimes lifelong, hormone replacement therapy is required.

Conclusion. Hypothalamic-pituitary-adrenal axis dysfunction associated with immune checkpoint inhibitor therapy remains underrecognized immune-related adverse event, requiring early recognition through clinician vigilance and screening algorithms to prevent adrenal crisis, improve quality of life and maintain cancer treatment efficacy. Multidisciplinary collaboration between oncologists and endocrinologists is particularly important in the care of these patients at all stages of treatment and follow-up.

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