FULMINANT DESTRUCTIVE PAINLESS THYROID-ITIS AFTER A SINGLE DOSE OF PEMBROLIZUMAB IN AN OBESE ELDERLY MAN LOADED WITH IODINE

Abstract: Destructive thyroiditis can occur following the use of Pembrolizumab or an iodine loading from iodinated contrast administration, and topical application of iodinated skin preparations. Immune checkpoint inhibitors (ICI), commonly used in cancer patients, are often accompanied by frequent CT scans with iodinated contrast or surgeries involving topical iodine-based preparations, such as povidone-iodine (Betadine). Additionally, ICI-induced overt hyperthyroidism has been associated more frequently with higher body mass index. However, the combined impact of these factors on thyroid dysfunction in a single patient has not been previously reported. We present the case of a 72-year-old obese male veteran with recurrent desmoplastic melanoma who developed rapidly progressive destructive thyroiditis following a single dose of Pembrolizumab. He received the therapy on day 0 and underwent repeated CT scans with iodinated contrast on days 8 and 35. Additionally, he had a recent excisional skin biopsy on his left forearm three days prior to Pembrolizumab administration (day -3). He developed overt hyperthyroidism on day 22 (TSH = 0.03 μU/mL, FT4 = 1.7 ng/dL) and peaked on day 29 post-ICI therapy (TSH = 0.01 μU/mL, FT4 = 3.6 ng/dL) . He remained hyperthyroid on day 51, then progressed to hypothyroidism by day 72 (TSH = 35.5 μU/mL, FT4 = 0.3 ng/dL), worsening further by day 99 (TSH = 97.4 μU/mL, FT4 = 0.1 ng/dL). The patient reported no thyroid pain and was initially reluctant to receive treatment. He maintained a normal heart rhythm, with a heart rate ranging from 67 to 103 bpm. Methimazole (10 mg/day) was administered for only two days (days 35 and 36), and levothyroxine replacement therapy was initiated on day 99. The patient received only one dose of Pembrolizumab throughout the course of his thyroiditis. ICI therapy was resumed on day 159 following a cycle of radiation therapy (administered from day 10 to day 72). A PET/CT scan performed on April 6, 2020, revealed progression of right facial melanoma. He passed away three months later. Abnormal thyroid function is associated with higher mortality and reduced life expectancy. Optimizing the metabolic state of cancer patients receiving ICIs may help reduce the incidence and severity of thyroid dysfunction, potentially improving overall survival and quality of life.