SAT-481 Pembrolizumab-Induced Thyroiditis with Negative Thyroid Peroxidase Antibody

Introduction: Immune checkpoint inhibitors (ICI) have reformed oncology treatment through its immunomodulatory effect on T-lymphocytes to target metastatic and locally advanced cancers but have been known to produce immune-related adverse events (irAEs). Thyroiditis is a well-documented endocrinopathy occurring in patients receiving ICI; however, a Thyroid Peroxidase Antibody (TPO Ab) negative case of ICI induced thyroiditis suggests that its pathogenesis is independent of antibody mediated thyroid destruction and more associated with an alternative immunoregulatory mechanism. Case Description: A 60-year-old Caucasian, male with a 37-year smoking history and lung adenocarcinoma with metastasis to the brain was referred to Endocrinology clinic for evaluation of suppressed thyroid stimulating hormone (TSH) level. Patient was treated with a four-month course of IV Pembrolizumab every three weeks. TSH was <0.015 (NL 0.465-4.680 IU/mL) four weeks before being seen at the office. TSH level was normal 2.359 before starting immunotherapy. Patient reported occasional anxiety and heat intolerance, but did not experience other hyperthyroid symptoms. Physical examination in office demonstrated no significant thyromegaly, nodules, or tenderness. Vital signs were normal. Thyroid function tests obtained during the office visit were consistent with subclinical hypothyroidism. TSH was mildly elevated 7.545 with normal Free T4 of 0.94 (NL 0.78 - 2.19 ng/dL) and normal Free T3 level of 3.61 (NL 2.77 - 5.27 pg/mL). TPO antibodies were negative. Four weeks later, patient developed overt hypothyroidism; TSH level was higher 12.437 with low Free T4 of 0.71. Patient was then complaining of fatigue and cold intolerance. A diagnosis of drug-induced thyroiditis from Pembrolizumab was made. The patient was prescribed levothyroxine 75 mcg daily and followed closely. Discussion: While literature exists documenting the rare side effect profile of ICI endocrinopathies, few studies illustrate the implications and correlations of TPO Ab negative findings in ICI induced thyroiditis. The role of thyroid autoantibodies in the presumed antibody mediated pathogenesis of thyroid abnormalities is unclear and warrants further longitudinal studies to determine its function in these patients. This case report hopes to both identify the deficit of pathophysiological knowledge contextualizing irAEs while encouraging current healthcare practitioners to continue close monitoring of patients receiving ICI.