SUN-582 - A Rare Case of Pembrolizumab-Induced Diabetic Ketoacidosis without Prior Hyperglycemia

Background:
Immune checkpoint inhibitors (ICIs), including pembrolizumab, are increasingly used in the treatment of non–small cell lung cancer (NSCLC) and have improved survival outcomes. However, ICIs can cause rare immune-related adverse events, including new-onset diabetes mellitus and diabetic ketoacidosis. Recognition is critical in these cases given the potential for rapid clinical deterioration. Here, we will discuss a case on how pembrolizumab caused a rare adverse event.

Case Presentation:
83-year-old female with a medical history significant for stage 4 NSCLC diagnosed in 09/2024 on pembrolizumab since 01/2025, hypertension, syndrome of inappropriate anti-diuretic hormone (SIADH), and chronic obstructive pulmonary disease (COPD) presented to the emergency department with complaints of malaise, nausea, and vomiting of 1 week. She endorsed an inability to tolerate any oral intake of both solids and liquids, immediately having a bout of emesis afterward. She also endorsed worsening polyuria and polydipsia over the last few days, shortness of breath, and disorientation. On arrival to the ED, the patient was alert and oriented to person, place, and date. However, she appeared in significant distress, with labored respirations. Point-of-care labs revealed significantly elevated blood glucose at 790 mg/dl and a venous blood gas revealed significant acidosis of pH 6.85. Labs were notable for serum potassium of 6.3 mmol/L, bicarbonate level of 2.5 mmol/L, and an elevated anion gap of 26.5 mmol/L. A beta-hydroxybutyrate level measured 11.46 mmol/L and Hgb A1C measured 7.4%. The RVP and CXR were unremarkable. Based on this patient's clinical presentation, she was found to be in new-onset DKA and was admitted to the ICU for further management. In the interim, autoantibodies were checked, and GAD-65 antibody and Insulin Auto antibody were both within normal limits. Once stable, the patient was transitioned to subcutaneous insulin, received diabetes education, and was discharged after 12 days with a diagnosis of pembrolizumab-induced autoimmune diabetes.



Conclusion:
Immune checkpoint inhibitor-induced diabetes is a rare, potentially fatal immune-related adverse event that can occur in individuals without a prior history of diabetes. As immune checkpoint inhibitors block the Programmed Death-1 (PD-1) immune cell pathway, this leads to unregulated activity of T cells that can kill cancer cells, but also healthy cells. T cells can mistakenly attack insulin-producing beta cells of the pancreas. Hence, it will cause new onset diabetes presenting with a Type-1 diabetic picture. This case highlights the importance of patient education and early recognition of hyperglycemic symptoms in patients receiving ICIs to prevent severe metabolic complications and improve patient outcomes.

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