C49-20 Concurrent Immune Checkpoint Inhibitor-Induced Thyroiditis and Pneumonitis Progressing to Cardiomyopathy and ARDS: A Fatal Multi-Organ Immune-Related Adverse Event

Abstract Introduction Immune checkpoint inhibitors (ICIs) improve survival across cancers but can cause immune-related adverse events (irAEs). Thyroiditis and pneumonitis are recognized as irAEs; their simultaneous presentation with progression to cardiomyopathy and acute respiratory distress syndrome (ARDS) is rare and diagnostic. Early recognition of multi-organ involvement and prompt immunosuppression are critical. Case Presentation A 60-year-old man with metastatic esophageal adenocarcinoma on recent ICI therapy presented with acute hypoxemic respiratory failure and progressive confusion. On arrival, oxygen saturation was in the 70s and improved transiently with non-invasive ventilation. Initial laboratory results showed leukocytosis and metabolic acidosis in the venous blood gas. Broad-spectrum antibiotics were started for possible sepsis, while ARDS management began in the medical ICU. Chest imaging demonstrated diffuse bilateral opacities. The differential included severe infectious pneumonia versus ICI-related pneumonitis, given the temporal proximity to ICI exposure and compatible radiographic pattern. Lung-protective ventilation, deep sedation, neuromuscular blockade, and prone positioning were instituted. High-dose corticosteroids were initiated for suspected immune-mediated pneumonitis. Concurrently, clinical features suggested endocrine irAE: laboratory testing supported thyroiditis, and transthoracic echocardiography revealed new systolic dysfunction concerning stress or inflammatory cardiomyopathy. The evolving picture of pulmonary and endocrine irAEs with cardiac involvement raised concern for a fulminant multi-organ process amplifying hypoxemia and shock risk. Despite multiple prone cycles and aggressive immunosuppression, oxygenation and compliance failed to improve meaningfully. After multidisciplinary evaluation and goals-of-care discussions with the family, the patient was transitioned to comfort-directed management and expired. Discussion This case illustrates a rare, fatal triad of ICI-associated thyroiditis and pneumonitis with evolving cardiomyopathy culminating in refractory ARDS. Although either pneumonitis or thyroiditis alone is well described, their concurrent occurrence with cardiac dysfunction can blur clinical signals, delay diagnosis, and limit response to standard ARDS bundles. Main takeaways include maintaining a high index of suspicion for multi-organ irAEs in any ICI-exposed patient with rapid respiratory decline; obtaining early endocrine and cardiac assessment when pulmonary irAE is suspected; initiating high-dose corticosteroids promptly while pursuing infectious evaluation; and engaging multidisciplinary teams early (oncology, endocrinology, cardiology, and critical care). Reporting such cases may inform recognition patterns, escalation of thresholds, and selection/timing of second-line immunosuppression in steroid-refractory disease. This abstract is funded by: None