A Triple Threat: Immune Checkpoint Inhibitor-Induced Diabetic Ketoacidosis, Myocarditis, and Adrenal Insufficiency in a Patient With Metastatic Melanoma

Immune checkpoint inhibitors (ICIs), such as ipilimumab and nivolumab, have revolutionized cancer therapy, particularly in advanced melanoma. By enhancing T-cell-mediated anti-tumor activity, these agents have significantly improved survival in metastatic disease. However, this immune activation can result in a range of immune-related adverse events (irAEs), which may affect virtually any organ system, sometimes with overlapping or atypical presentations. Endocrine irAEs, such as hypophysitis, thyroid dysfunction, and adrenalitis, are relatively well-described. Less commonly, ICIs can precipitate insulin-dependent diabetes mellitus or autoimmune myocarditis - both of which are rare but potentially life-threatening. These complications may present non-specifically, such as with fatigue or malaise, and are often under-recognized. This case highlights the importance of maintaining a high index of suspicion for multiple concurrent irAEs in patients on immunotherapy, even in the absence of overt clinical signs. Early recognition and prompt immunosuppressive therapy can significantly reduce morbidity and improve outcomes.