SUN-520 - Pembrolizumab-Induced Diabetes Mellitus: Early Recognition to Avoid Diabetic Ketoacidosis

Background
Pembrolizumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, enhances antitumor immunity by preventing PD-1 interaction with PD-L1 and PD-L2. It is FDA-approved for select malignancies, including triple-negative breast cancer (TNBC). Although pembrolizumab improves event-free survival, immune-related adverse events remain clinically significant. Immune checkpoint inhibitor–associated diabetes mellitus (ICI-DM) is a rare but serious complication with an incidence of 0.6–1.4%. Rapid T-cell–mediated pancreatic β-cell destruction leads to abrupt insulin deficiency. Most reported cases present with diabetic ketoacidosis (DKA), often requiring insulin infusion and intensive care. Routine glucose surveillance and early detection may allow intervention before severe metabolic decompensation.
Case
A 62-year-old woman with TNBC on her third cycle of pembrolizumab and no prior history of diabetes was referred to the emergency department after outpatient laboratory testing revealed glucose levels beyond glucometer range. She reported three days of polydipsia and polyuria without abdominal pain, nausea, vomiting, dyspnea, altered mental status, or steroid exposure. Laboratory testing revealed a serum glucose of 600 mg/dL, venous pH 7.32, an elevated beta-hydroxybutyrate (>4.5 mmol/L), and 3+ urine ketones, consistent with mild DKA in new-onset diabetes. Hemoglobin A1c was 8.7%, renal function was preserved, and the patient remained hemodynamically stable. Early endocrinology consultation led to prompt treatment with intravenous fluids and subcutaneous basal-bolus insulin. The hyperglycemia and ketosis resolved without requiring insulin infusion or progressing to severe acidosis. C-peptide was markedly suppressed (0.12 ng/mL), supporting acute β-cell failure. Further testing revealed severe hypothyroidism (TSH 69 mIU/L, free T4 0.29 ng/dL), suggesting a broader immune-mediated endocrinopathy. The patient was discharged on basal insulin and levothyroxine with close outpatient follow-up.
Conclusion
This case illustrates that ICI–DM with biochemical diabetic ketoacidosis can present with minimal symptoms. Routine surveillance with basic metabolic labs and early endocrine referral may allow interception before progression to severe DKA requiring insulin infusion or expensive ICU-level care. Given that a majority of reported ICI-DM cases present in DKA, maintaining a high index of suspicion and implementing proactive glucose monitoring during checkpoint inhibitor therapy are critical to preventing severe metabolic decompensation and enabling safer transition to outpatient management.

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