Abstract
Disclosure: Y. Prystupa: None.
Introduction: Immune checkpoint inhibitors (ICIs), including durvalumab, have markedly advanced cancer therapy but are increasingly associated with immune-related adverse events (irAEs), particularly those involving the endocrine system. While thyroid dysfunction is the most common endocrine irAE, occurring in up to 20% of patients, new-onset type 1 diabetes mellitus (T1DM)—known as checkpoint inhibitor-induced diabetes (CPI-DM)—is much rarer, affecting ∼ 1% of ICI recipients. The concurrent development of multiple endocrine irAEs is especially rare and can impact patient outcomes, quality of life, and long-term disease management. Most reported cases of CPI-DM involve PD-1 inhibitors such as pembrolizumab or nivolumab. This case contributes to the growing literature by describing a patient who developed both new-onset autoimmune diabetes and exacerbation of preexisting hypothyroidism during treatment with durvalumab—a PD-L1 inhibitor less commonly associated with this combination of toxicities. Clinical Case A 64-year-old male with metastatic squamous cell carcinoma of the lung, post-chemoradiation and undergoing treatment with durvalumab, presented with fatigue, lethargy, and anorexia. Laboratory evaluation revealed severe hyperglycemia, with an HbA1c of 12.1% (normal range: 4.0-5.6%). Further testing showed positive glutamic acid decarboxylase (GAD65) antibodies (12.7 IU/mL; normal <5.0 IU/mL), confirming autoimmune diabetes. Thyroid function tests showed markedly elevated TSH (49.10 mIU/L; normal range: 0.27-4.20) and low free T4 (0.20 ng/dL; normal range: 0.80-1.70), consistent with significant hypothyroidism. The patient had no personal or family history of diabetes, and his hypothyroidism had been well-controlled on levothyroxine prior to ICI initiation. Together, these findings led to a diagnosis of CPI-DM and exacerbation of preexisting hypothyroidism, approximately four months after initiating durvalumab. The patient was started on subcutaneous insulin, and his levothyroxine dose was increased. He remains insulin dependent. Conclusion This case underscores the potential for durvalumab to trigger simultaneous, severe, and potentially irreversible endocrine complications, such as CPI-DM and exacerbation of hypothyroidism. Given the rarity and clinical burden of these toxicities, clinicians should maintain a high index of suspicion and routinely monitor glucose and thyroid function in all patients receiving ICIs, regardless of prior endocrine history. The unpredictable onset and severity of these irAEs highlight the need for further research into predictive biomarkers, underlying mechanisms, and standardized screening and surveillance strategies. As more cases are recognized, this report contributes to the growing understanding of the timing, spectrum, and clinical impact of ICI-associated endocrine toxicities.
Presentation: Sunday, July 13, 2025