MON-408 Severe Hypothyroidism with Impending Myxedema Coma after Pembrolizumab Therapy

Abstract Disclosure: F.N. Connor-Recio: None. O. Rivera-Zayas: None. J. Colón Castellano: None. Immune checkpoint inhibitors (ICIs) have been proven effective in the treatment of many malignancies by harnessing the immune system. However, a wide spectrum of immune-related adverse effects (irAEs) has been reported, including endocrinopathies most commonly thyroid disorders. Pembrolizumab, a humanized monoclonal IgG4 kappa isotype antibody against PD-1, can disrupt the engagement of PD-1 with its ligands and impede inhibitory signals in T cells, with resultant tumor recognition by cytotoxic T cells. Thyroid disorders may occur even after the first therapeutic dose of ICI therapy, with the median time onset of 6-10 weeks after initiation but as early as 7 days. These pose challenges in both diagnostic and treatment. This is the case of a 72 y/o male with history of hypertension, atrial fibrillation on apixaban and amiodarone, chronic obstructive pulmonary disease GOLD 2A, hyperlipidemia, chronic kidney disease stage 2, seizures, oropharyngeal dysphagia, and stage IV lung squamous cell carcinoma with metastasis to the brain that failed to conventional therapy and was started on pembrolizumab 6 weeks ago. The patient came to our emergency department due to acute shortness of breath and lightheadedness, associated with hoarseness for the past 2 months. Vital signs with mild hypothermia of 35.10 C, blood pressure of 153/113, pulse 87bpm, and hypoxemia. Physical exam with diffuse bilateral expiratory wheezes. Pertinent laboratories remarkable for elevated TSH at 109.8 uIU/mL (normal range: 0.46-4.98 uIU/mL), low free T4 0.101 ng/dL (normal range: 0.71-1.85 ng/dL) and euvolemic hypotonic hyponatremia. Thyroid ultrasound remarkable for atrophic changes, and a hypoechoic irregular nodule at level 3 of the right side of the neck felt to represent metastatic lymphadenopathy. Patient was admitted to ICU with diagnostic impression of severe hypothyroidism with impending myxedema coma suspected secondary to pembrolizumab and chronic amiodarone use. Patient was initially managed with IV bolus of hydrocortisone 100 mg and then started on IV levothyroxine (100 mcg once then 50 mcg daily) and Hydrocortisone IV drip for 3 days. Patient was then transferred to ward once respiratory failure resolved to continue TSH and free T4 monitoring. Subsequent TSH values decreased from 109.8 to 65.7 uIU/mL and free T4 levels increased from 0.101 to 0.469 ng/dL and levothyroxine 125 mcg PO daily was started. Patient was later discharged to follow up with endocrinology service as outpatient. The occurrence of anti-PD-1–induced thyroid irAEs is high, although the underlying mechanism is not completely understood. Therefore, it is important to monitor thyroid function test closely in patients receiving these therapies for prompt recognition and treatment. Presentation: Monday, July 14, 2025