- Pembrolizumab can induce abrupt type 1 diabetes causing diabetic ketoacidosis despite negative GAD, IA-2, and islet cell antibodies and undetectable C-peptide.
- Concurrent hyperthyroidism with positive thyroid peroxidase antibodies indicated autoimmune thyroiditis occurring alongside pembrolizumab induced diabetes.
- Baseline screening, ongoing endocrine monitoring, high clinical suspicion, patient education, and multidisciplinary care are essential to detect and manage immune-related adverse events early.
Cureus. 2026 Aug 24;18(8):e115106. doi: 10.7759/cureus.115106. eCollection 2026 Aug.
ABSTRACT
Pembrolizumab, a programmed cell death protein 1 (PD-1) immune checkpoint inhibitor, is commonly used in the treatment of squamous cell carcinoma, offering improved survival and tumor response. However, it can rarely lead to immune-related adverse events (irAEs), some of which may be significant. We report a 62-year-old male with squamous cell carcinoma of the lung, a 40-pack-year smoking history, prediabetes, and coronary artery disease, who presented with polydipsia, polyuria, and weakness. He was diagnosed with sudden-onset diabetic ketoacidosis. Laboratory workup revealed negative glutamic acid decarboxylase (GAD), IA-2, and islet cell antibodies, as well as an undetectable C-peptide level, consistent with immune checkpoint inhibitor-induced type 1 diabetes. Concurrently, the patient developed hyperthyroidism with positive thyroid peroxidase (TPO) antibodies, suggesting autoimmune thyroiditis. This case underscores the importance of baseline screening and ongoing monitoring for endocrine irAEs during immunotherapy. Clinicians should maintain a high index of suspicion, even in patients without prior autoimmune disorders. Early recognition, patient education, and coordinated multidisciplinary care are critical for reducing complications and improving outcomes.
PMID:42781218 | PMC:PMC13600691 | DOI:10.7759/cureus.115106
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