Adrenal insufficiency induced by immune checkpoint inhibitors anticancer therapy

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and significantly improved the prognosis of patients with advanced tumors. ICIs are monoclonal antibodies that inhibit regulatory proteins, namely cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), Programmed Cell Death 1 (PD-1), and its Ligand (PD-L1). The blockage of the key regulatory signaling pathways allows cytotoxic T lymphocytes to reestablish an effective anticancer response. Despite significant clinical benefits, ICIs may electively provoke toxicity of the endocrine system, including adrenal insufficiency. Recognizing drug-induced adrenal cortex insufficiency may be challenging due to miser manifestations and non-specific clinical signs. Therefore, diagnosing adrenal dysfunction requires careful monitoring of cortisol and adrenocorticotropic hormone levels during ICIs therapy. This review presents up-to-date research on ICIs-induced adrenal insufficiency. Studies have shown that early detection of deviations from the norm increases the chances of survival of ICI-triggered autoimmune adrenalitis, the rare but potentially life-threatening complication of anticancer therapies.