SAT-516 A Severe Case of Pembrolizumab-Induced Thyroiditis

Abstract

Pembrolizumab, a programmed death 1 (PD-1) inhibitor used for advanced malignancies, can be associated with thyroid dysfunction.1-2 Specifically, thyroiditis occurs in nearly 2.3% of individuals.2 The hyperthyroid phase is typically non-severe, requiring only beta blockers. Our case illustrates that conservative therapies may be ineffective in pembrolizumab-induced severe thyroiditis.A 54-year-old woman with metastatic non-small cell lung cancer with normal baseline TSH received pembrolizumab. She was hospitalized nearly 30 days later with nausea, vomiting and tachycardia. Labs showed TSH <0.02 mcIU/mL (normal 0.3-4.7), free T4 >7 ng/dL (normal 0.8-1.7) and free T3 2105 pg/dL (normal 222-383). TSH receptor antibody was undetectable; hyperthyroidism was attributed to pembrolizumab. Metoprolol was initiated. She was re-hospitalized three days later with persistent symptoms and inability to tolerate orals. Labs again showed severe hyperthyroidism and TPO antibody 201 IU/mL (normal ≤ 20). Burch-Wartofsky score was 25. Given her symptom severity, propylthiouracil, hydrocortisone, and propranolol were initiated to reduce peripheral T4 to T3 conversion. A cortisol of 5 mcg/dL (collected 9:47AM) further supported the use of hydrocortisone. Following a normal Cosyntropin stimulation test, hydrocortisone was discontinued. Her symptoms improved but hypothyroidism developed 68 days after pembrolizumab initiation. Propylthiouracil was discontinued; levothyroxine was started. Her TFTs ultimately normalized.Beta blockers are the mainstay of treatment of the hyperthyroid phase of PD-1 inhibitor-related thyroiditis, though case reports have described use of glucocorticoids, anti-thyroid drugs and iodine.2 -4 In our patient, severe thyrotoxicosis was not responsive to beta blockers. Consideration of additional therapies is reasonable in these cases.