ODP527 To Treat or Not to Treat Pembrolizumab-Induced Thyroiditis: Using Common Terminology Criteria for Adverse Events as a Decision-Making Aid

Abstract

Abstract Introduction Programmed cell death-1 (PD-1) checkpoint inhibitors are immunotherapeutic agents that are used to treat advanced malignancies including breast cancer. The adverse effects of these medications include thyroid and pituitary dysfunction and may be treated with glucocorticoids, which may cause steroid-induced effects such as hyperglycemia, osteoporosis, and adrenal suppression. The Common Terminology Criteria for Adverse Events (CTCAE) widely used by oncologists for management can support treatment decisions by endocrinologists in patients undergoing treatment with PD-1 checkpoint inhibitors. Case Description A 42-year-old female with stage IIIc high-grade triple negative left breast invasive ductal carcinoma was started on pembrolizumab immunotherapy (PD-1 inhibitor). Prior to starting treatment, the patient's thyroid function tests were normal: free T4 0.93 ng/dL (normal range [NR] 0.89-1.76 ng/dL) and thyroid-stimulating hormone (TSH) 1.42 uIU/mL (NR 0.55-4.78 uIU/mL). Two weeks later, she developed heat intolerance, diarrhea, weight loss, and dysphagia. At that time, thyroid tests were consistent with thyrotoxicosis with elevated total T3 644.6 ng/dL (NR 60-180 ng/dL) and totalT4 >12. 00 ng/dL with suppressed TSH 0. 01 uIU/mL. Despite negative TSH receptor antibody and thyroid-stimulating immunoglobulin, CT scan of the neck showed diffuse enlargement of the thyroid gland and thickening of the extraocular muscles. On physical examination she had mild exophthalmos. The etiology of thyrotoxicosis was initially thought to be Graves’ disease, but thyroiditis could not be ruled out. Treatment with methimazole and beta blockers was initiated. Three weeks after methimazole was started, her symptoms improved significantly, with repeat thyroid function tests: TSH 3.64 uIU/mL and free T4 1.29 ng/dL. Methimazole was held. Four weeks later, the second dose of pembrolizumab was administered. Later that day, repeat thyroid function tests showed high TSH 53.12 uIU/ml, and low T4 0.55 ng/dL with negative thyroid-stimulating immunoglobulin and thyroid peroxidase antibodies, consistent with thyroiditis. Endocrinology and Oncology teams discussed the CTCAE determining that the severity of thyroiditis was grade 2 (moderate symptoms, able to perform activities of daily living, TSH persistently above 10 uIU/L). Pembrolizumab was continued and hypothyroidism was treated with levothyroxine. Discussion CTCAE is used by oncologists to aid in treatment decisions in patients treated with PD-1 inhibitors. Endocrinologists should consider using the CTCAE grading (severity) scale for each adverse event. Adoption and utilization of the CTACE severity scale by endocrinologists may lead to a more standardized and systematic approach for treatment of thyroid disorders associated with PD-1 inhibitor immunotherapy Presentation: No date and time listed