Isolated Adrenocorticotropic Hormone (ACTH) Deficiency as an Immune-Related Adverse Event Following Combination Immune Checkpoint Inhibitor Therapy

Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare condition characterized by the sole impairment of ACTH secretion among the various hormones produced by the pituitary gland. This leads to secondary hypoadrenocorticism, manifesting symptoms such as fatigue, anorexia, weight loss, and altered consciousness. Recently isolated ACTH deficiency has emerged as an immune-related adverse event (irAE) associated with immune checkpoint inhibitors (ICIs). In this report, we detail a case of isolated ACTH deficiency as a result of irAE. A 65-year-old man received nivolumab and ipilimumab combination therapy for esophageal cancer and approximately six weeks later, presented fatigue and anorexia, and was shown hyponatremia and hyperkalemia on blood test, and was diagnosed as isolated ACTH deficiency. Retrospective examination indicated an increase in eosinophils and a slight decrease in sodium levels shortly before thyrotoxicosis was diagnosed. These findings suggest the possibility of mild hypoadrenocorticism, potentially due to decreased ACTH secretion, existing prior to the recognition of adrenal insufficiency symptoms. Healthcare providers should maintain a heightened vigilance for eosinophilia and electrolyte imbalances during the administration of ICIs. The detection of even subtle abnormalities in these parameters should prompt immediate consultation with an endocrinologist.