Case Presentation: A 56-year-old male with stage IV small cell lung cancer and liver metastasis presented with abdominal pain, nausea, vomiting, shaking, increased thirst, urinary frequency, and palpitations. He had recently completed cycle 3 of carboplatin, etoposide, and atezolizumab. On exam, he was afebrile, pulse 124, BP 132/80. Labs revealed WBC 15.3 (post-Neulasta), lactate 4, glucose 560, anion gap 31, CO2 13. Urinalysis was positive for 4+ glucose and 4+ ketones. Infectious workup was negative. Thyroid studies showed TSH < 0.01, free T4 >7.8, T3 13.5, thyroid peroxidase autoantibodies 75, and negative thyroid-stimulating immunoglobulin. A1c was 7.4, C-peptide 0.16. Imaging, including chest X-ray and CT abdomen/pelvis, was unremarkable. He was admitted to the ICU for new-onset diabetic ketoacidosis (DKA), treated with IV fluids and insulin drip, and transitioned to basal-bolus insulin. Endocrinology was consulted. He was also started on methimazole for new-onset hyperthyroidism and discharged with new insulin requirements.
Discussion: This case demonstrates that immune checkpoint inhibitors (ICIs), such as atezolizumab (PD-L1 inhibitor), can induce new-onset autoimmune diabetes mellitus and hyperthyroidism as immune-related adverse events (irAEs). The patient developed both DKA, due to insulin-deficient diabetes, and thyrotoxicosis, due to hyperthyroidism, after several cycles of ICI-based therapy for metastatic small cell lung cancer.ICI-induced diabetes mellitus is rare, occurring in about 1% of patients, and typically presents as DKA with hyperglycemia, elevated anion gap, and low C-peptide, reflecting beta-cell destruction. Onset is usually within 2-4 months of starting therapy, and most patients require lifelong insulin. Endocrine irAEs, such as hyperthyroidism, are more common, affecting 2-3% of patients. ICI-induced hyperthyroidism may be transient and often progresses to hypothyroidism.Recognition of these endocrinopathies is critical, as they can present with life-threatening complications and may occur simultaneously. The clinical presentation can mimic classic autoimmune endocrine disease, but the timing in relation to ICI therapy is a key diagnostic clue. Prompt diagnosis and management are essential to prevent morbidity and mortality. Multidisciplinary care involving endocrinology and oncology is recommended for optimal management and to support ongoing cancer therapy when possible.
Conclusions: This case highlights the need for vigilance in recognizing and promptly managing ICI-induced endocrine toxicities, such as DKA and thyrotoxicosis. Early diagnosis and multidisciplinary intervention can significantly improve outcomes for patients receiving immunotherapy.