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Article Abstract

Background/objective: Thyroid immune-related adverse events (irAEs) are a common occurrence with the use of anti-programmed cell death-1 agents such as pembrolizumab. Anti-programmed cell death-1-induced thyroid storm in the absence of autoimmune thyroid disease is a rare but potentially fatal complication. This report aims to highlight the varied spectrum of thyroid irAEs, emphasize the importance of early detection, and discuss the challenges involved in diagnosing and managing these conditions.

Case Report: A 50-year-old African American woman with type 2 diabetes mellitus, hypertension, and stage IIIc triple-negative breast cancer receiving neoadjuvant chemotherapy and pembrolizumab presented with severe thyrotoxicosis. Her Burch-Wartofsky score was >45, indicating thyroid storm. Thyroid antibodies were negative. She was treated with propylthiouracil, hydrocortisone, and beta-blockers, later transitioning to methimazole. She progressed to hypothyroidism and requiring long-term levothyroxine replacement. Eight months later, her thyroid function normalized, and she continued her cancer treatment with pembrolizumab, remaining asymptomatic and under regular follow-up.

Discussion: Awareness of the spectrum of thyroid irAEs is crucial because they can range from subclinical disease to more severe manifestations such as thyroid storm, even in the absence of autoimmune thyroid disease. Early detection and management of these conditions can significantly improve patient outcomes and ensure the safe continuation of immunotherapy treatments.

Conclusion: Pembrolizumab precipitated thyroiditis culminating in thyroid storm, as evidenced by the temporal relationship with therapy and development of severe thyrotoxicosis followed by hypothyroidism and the lack of thyroid autoantibodies. Clinicians should remain vigilant regarding the potential for thyroid storm in patients undergoing pembrolizumab treatment.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12332487PMC
http://dx.doi.org/10.1016/j.aed.2025.04.008DOI Listing

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