LAUSR

Abstract BACKGROUND: The anti-PD1 monoclonal antibody nivolumab, approved for treatment of several cancers, is associated with ~ 3% rate of hyperthyroidism. Most cases are due to destructive thyroiditis. Stimulating antibodies against the TSH receptor (TSH-R) have not been reported in nivolumab-associated thyroiditis. CLINICAL CASE: A 68-year old man developed hyperthyroidism several months after completion of nivolumab for renal carcinoma. Thyroid function tests were normal prior to nivolumab. Only 4 doses of nivolumab were given over 2 months due to poor tumor response. During this time the patient’s TSH declined minimally (baseline 1.06 uIU/mL, subsequent values 0.35-0.51uIU/mL, normal 0.6-3.3 uIU/mL) and Free T4 remained within or close to the normal reference range. The patient had no symptoms or signs of hyperthyroidism. One month after the final dose of nivolumab, TSH increased slightly to 4.3 uIU/mL. However, 3 weeks later, TSH became suppressed and Free T4 rose to 4.92 ng/dL (0.71-1.4). The patient was asymptomatic. Exam was unremarkable except brisk deep tendon reflexes. Ten days later, free T4 rose further to > 6.99 ng/dL and remained similarly elevated, with Free T3 of > 22.8 pg/mL (2.45-5.93 pg/mL), for several more weeks. During this time, the patient lost 12 pounds and complained of poor appetite. He remained hemodynamically stable with beta-blockers. Antibodies against thyroid peroxidase (TPO) were negative, but antibodies against the TSH-R (thyroid-stimulating immunoglobulin or TSI) were elevated at 1.5 (< 1.3). Because of the elevated TSI and the persistent marked elevation of Free T4 and FT3 for > 1 month after onset of hyperthyroidism, thyroid uptake and scan were obtained to evaluate for Graves’ hyperthyroidism. The 24-hour uptake of I-131 was 0.7% and the scan showed almost no tracer uptake in the thyroid, consistent with thyroiditis. Shortly thereafter, the FT4 and FT3 began to decrease, and the patient’s weight loss stabilized. The Free T3 normalized 2 months after the hyperthyroidism was first detected, and the Free T4 stabilized to just above the reference range, without specific treatment. The TSI remained positive at 1.8. CONCLUSION: This is the first reported case, to our knowledge, of nivolumab-associated thyroiditis with positive TSH-R stimulating antibodies and negative anti-TPO antibodies. Thus, antibody profile alone should not be used to diagnose Graves’ disease in a patient receiving nivolumab. REFERENCE: (1) Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, Tolaney SM. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(2):173