MON-452 Thyroid Dysfunction and Myxedema Coma with Pembrolizumab: A Call for Enhanced Monitoring

Abstract Disclosure: M. Yabe: None. Y. Ng: None. S. Savithri Nandeesha: None. H. Khalid: None. J. Giunta: None. R.J. Silver: None. D.C. Rafii: None. The use of immune checkpoint inhibitors (ICIs) such as Pembrolizumab has revolutionized cancer treatment, offering significant benefits for patients with various malignancies. However, the immunomodulatory effects of these therapies can result in a range of immune-related adverse events, including thyroid dysfunction. Pembrolizumab, along with other ICIs targeting PD-1 or PD-L1, has been well-documented to cause both hypo- and hyperthyroidism, with hypothyroidism being the more common manifestation. These thyroid dysfunctions can develop at any point during treatment, often presenting with subtle symptoms such as fatigue, weight gain, and cold intolerance, or in more severe cases, life-threatening conditions such as myxedema coma. An 88-year-old male with a history of recently diagnosed stage IIIc acral lentiginous melanoma of the right plantar foot was admitted for progressive neurological symptoms, including slurred speech and obtundation. The patient had started his first cycle of Pembrolizumab four months prior and was due for his fifth cycle. A stroke workup, including MRI, excluded acute intracranial pathology. Laboratory findings revealed elevated serum thyrotropin (43.5 uIU/mL) and undetectably low free thyroxine levels. Despite aggressive intravenous thyroid hormone and steroid replacement, the patient developed persistent bradycardia (down to 30 bpm) and hypothermia (33.1°C), requiring intensive care with forced-air warming blanket, dopamine infusion, and permanent pacemaker placement. Ultimately, the patient’s thyroid function normalized, and his neurological symptoms improved, allowing for discharge to acute rehabilitation with endocrinology follow-up. Despite the established association between Pembrolizumab and thyroid dysfunction, there is currently no universally agreed-upon guideline on how frequently thyroid function should be monitored in patients undergoing ICI therapy. Existing recommendations suggest monitoring thyroid function at baseline and periodically during treatment, but the optimal frequency remains unclear. This uncertainty poses a significant challenge in clinical practice, as the onset of thyroid dysfunction can be insidious, and delays in detection and treatment may lead to severe outcomes. This case emphasizes the importance of close and frequent monitoring of thyroid function in patients receiving ICIs. Furthermore, there is a pressing need for a larger, multi-center study to establish evidence-based guidelines for thyroid function monitoring in this patient population. Such guidelines would help clinicians detect thyroid dysfunction early, enabling timely interventions and improving patient safety during immunotherapy. Presentation: Monday, July 14, 2025