Washington University/Barnes Jewish Hospital, Missouri
Disclosure(s): No relevant financial relationship(s) to disclose.
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering significant survival benefits across various malignancies. However, immune-related adverse events (irAEs), including endocrinopathies, can lead to significant morbidity and mortality. This case highlights the importance of early recognition and management of ICI-induced diabetes mellitus (ICI-DM), a rare but potentially life-threatening irAEin a patient receiving adjuvant nivolumab.
Description: A 76-year-old male with a past medical history of stage 2 chronic kidney disease, longstanding CLL (Rai stage 0), muscle-invasive urothelial carcinoma (MIUC) presented with confusion preceded by nausea, vomiting, diarrhea, polydipsia, polyuria, and weight loss.
Labs showed glucose 990 mg/dL, anion gap metabolic acidosis (pH 7.18, bicarbonate 7, anion gap 36), and β-hydroxybutyrate 10.8 mmol/L, consistent with diabetic ketoacidosis (DKA). Additional findings included Cr 1.86 mg/dL; baseline 1.1–1.2), K⁺ 6.9 mmol/L, WBC 19.9×10⁹/L, and lipase (918 U/L). A1C was 8.4% up from 5.6% five months prior. Imaging was unremarkable. He was resuscitated with intravenous fluids and started on insulin infusion, treated for hyperkalemia, empirically started on antibiotics, and admitted to the ICU.
C-peptide was low at .55, and GAD-65 antibodies were negative. ICI-DM was diagnosed. After resolution of DKA, he was transitioned to a basal-bolus insulin regimen. He was discharged on hospital day 3 after receiving diabetes education with endocrinology follow up. Immunotherapy was held after oncology discussion, with plans for surveillance imaging before reassessment.
Discussion: As immune checkpoint inhibitor (ICI) use expands, awareness of irAEs has grown. Endocrinopathies account for approximately 10–15% of irAEs, while ICI-DM is less common, with an incidence of 0.2–1.4%. Presentations are often fulminant, with diabetic ketoacidosis (DKA) as a frequent initial manifestation, making prompt recognition essential. Autoantibodies such as GAD65, IA-2, and ZnT8 are detected in only ~50% of cases. ICI-DM is typically irreversible, resistant to corticosteroids, and requires lifelong insulin. Notably, some studies suggest irAEs—including ICI-DM—may correlate with improved survival in ICI-treated patients and immunotherapy can be continued.
