SAT-485 Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case Series

Variations in the Time Course of Pembrolizumab-Induced Thyroiditis: A Case Series Introduction: Thyroid dysfunction is reported in 5 - 9.5 % of patients treated with Pembrolizumab, one of the PD-1 immune checkpoint inhibitors. However, the underlying mechanism of Pembrolizumab-induced thyroid disorders remains unclear. We present 3 clinical cases with Pembrolizumab-induced painless thyroiditis. They initially presented with thyrotoxicosis, but later converted to hypothyroidism. The onset of thyrotoxicosis after the treatment and time course of changing in thyroid function were varied among these cases. All three cases had normal thyroid function prior to the treatment. Case 1: 63-year-old M with bladder cancer, NSCLC and multiple brain metastases developed overt thyrotoxicosis with TSH 0.02 (0.34 - 4.82 mIU/mL) and Free T4 2.2 (0.8 - 1.5 ng/dL) at 108 days after the first cycle of Pembrolizumab. He had high TgAb (856) and TPO antibodies (196). In 14 days, he converted to hypothyroidism confirmed by TSH 14.6 and Free T4 0.8. Patient was started on Levothyroxine. Case 2: 69-year-old M with Stage IV NSCLC presented with thyrotoxicosis (TSH 0.01, Free T4 1.9) at days 41 after starting Pembrolizumab. TPO antibodies and TgAb were negative. During 51 days of follow up, he converted to hypothyroidism (TSH 8.89 and continued to trend up above 60). He eventually required levothyroxine therapy. Case 3: 57-year-old M with invasive verrucous squamous cell carcinoma of the perineum, urethra and prostate had normal TSH at baseline. Within 39 days after the first dose of pembrolizumab, TSH dropped to 0.013 and Total T4 increased to 14.8 (4.5 - 12.1 ug/dL), consistent with overt hyperthyroidism. In 108 days, patient developed hypothyroidism with Free T4 0.7. Discussion: All 3 cases we present did not have overt signs or symptoms of hyperthyroidism. Thyrotoxicosis spontaneously resolved without requiring steroid treatment. Studies suggest symptomatic treatment of beta blockers in cases of tachycardia, otherwise steroid use is not routinely recommended in PD1-induced thyroiditis. One cohort study analyzed the dynamic course of thyroid functions in patients receiving Pembrolizumab. Among the patients who developed thyrotoxicosis while on PD-1 inhibitor therapy, median onset time was 47 days (14–447 days). The median time for transition from thyrotoxicosis to hypothyroidism was 42 days (21–169 days). Conclusion: Our case series highlight the variations in the time course and nature of the Pembrolizumab-induced thyroiditis. Clinicians should be aware of the relatively short period of fluctuations of thyroid functions in patients treated with PD-1 inhibitors. References: Lee, Hyunju et al. “Characterization of Thyroid Disorders in Patients Receiving Immune Checkpoint Inhibition Therapy.” Cancer Immunology Research 5, no. 12 (2017): 1133–40. https://doi.org/10.1158/2326–6066.cir-17–0208.