Secondary Adrenal Insufficiency and Multisystem Endocrinopathy Following Immune Checkpoint Inhibitor Therapy

ABSTRACT: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, including malignant melanoma. However, ICIs are associated with immune-related adverse events (irAEs), including hypophysitis, secondary adrenal insufficiency, thyroid disorders, and insulin-dependent diabetes. We present the case of a 60-year-old male with a history of autoimmune disorders, including primary hypothyroidism and giant-cell arteritis, who developed diabetes mellitus requiring insulin therapy after 6 weeks of treatment, eosinophilic asthma after 10 weeks, and who was admitted after 28 weeks of therapy with secondary adrenal insufficiency due to suspected ICI-associated isolated adrenocorticotrophic hormone (ACTH) deficiency. Pituitary magnetic resonance imaging showed no abnormalities. After several surgeries for melanoma and basal cell carcinoma, his current treatment includes hydrocortisone, levothyroxine, and insulin therapy. This case highlights the complexities in diagnosing and managing endocrinopathies associated with ICI therapy. As ICIs become more widely used, endocrine irAEs such as hypophysitis and isolated ACTH deficiency are expected to become increasingly common. A multidisciplinary approach is key to minimizing complications. While endocrine irAEs may require prompt hormone replacement, they rarely justify discontinuation of ICI therapy, whose benefits often outweigh the risks.