A Rare Case of Immune Checkpoint Inhibitor-Induced Diabetic Ketoacidosis

Introduction/Background:

Immune checkpoint inhibitors (ICI) are being incorporated in treatment of various malignancies, activating T-cell responses against tumor cells, but occasionally triggering immune related adverse events (irAEs) by inadvertently attacking healthy tissue. Endocrinopathies due to ICI occur in 10% of patients, frequently manifesting as hypophysitis or thyroid dysfunction. ICI-induced diabetes is much rarer, with a 0.45% prevalence, as noted in a cohort study of 14,328 patients between 2010-2022 (1). Early detection is difficult due to nonspecific symptoms. This report details a case of ICI-induced diabetes and diabetic ketoacidosis (DKA) caused by ipilimumab and nivolumab therapy.

Description:

A 48-year-old female with metastatic ovarian clear cell carcinoma, receiving ipilimumab and nivolumab treatment for the past three months, presented with nausea, vomiting, anorexia, and polydipsia for a week. She had prior ICI-induced hypophysitis, requiring prolonged steroids. On admission she was alert and oriented, but lethargic. Vitals were notable for tachycardia and hypertension. Labs confirmed DKA with hyperglycemia of 492 (70-99 mg/dL), metabolic acidosis with pH 7.22 (7.35-7.45 units), bicarb 13 (21-32 mmol/L), anion gap 26 (7-19 mmol/L), and ketosis with beta-hydroxybutyrate >8 (0.0-0.3 mmol/L). C-peptide was 0.1 (0.8-3.9 ng/mL), indicating lack of insulin production. She received fluids, electrolyte repletion, and insulin drip before transitioning to basal-bolus insulin for ICI-induced diabetes. Post discharge, she is now followed by endocrinology and uses a continuous glucose monitor to guide insulin requirements. Her immunotherapy is temporarily held and may be discontinued given multiple irAEs.

Discussion:

This case highlights the insidious nature of ICI-induced diabetes. Unlike other irAEs treated with a steroid course, endocrine toxicities can require lifelong hormone replacement. It is important clinicians recognize these irreversible effects and counsel patients accordingly. Endocrinopathies typically emerge 14.5 weeks after ICI initiation but can occur within a week or years later. Cohort studies have shown that the incidence of ICI-induced diabetes is 124.8 per 100,000 person-years, a 7-fold increase compared to type I diabetes in ICI-naïve patients (1). Combination ICI therapy and preexisting type 2 diabetes further heighten the risk, making frequent screening and early endocrinology evaluation essential to prevent life-threatening presentations such as DKA.