Abstract Disclosure: M. Windham: None. S.K. Majumdar: None. Introduction: Lyme disease, a common tick-borne illness, causes multiorgan inflammation and dysfunction. It commonly affects the musculoskeletal, neurologic, cardiovascular, and integumentary systems. The endocrine system is rarely involved. We report a case of Lyme-associated thyroiditis in an otherwise healthy 41-year-old man. Case: A 41-year-old man with a history of hypertension, gastroesophageal reflux and a known BRCA2 mutation presented to the emergency department due to one week of frequent palpitations, fatigue, dyspnea on exertion, and dry cough. Laboratory testing revealed thyrotoxicosis with an undetectable TSH (n 0.270—4.200 µIU/mL), FT4 of 7.04 ng/dL (n 0.80—1.70 ng/dL), and TT3 of 253 ng/dL (n 92.0—224 ng/dL). He denied any recent illnesses or pain in his thyroid. Further work up revealed negative TSI and TPO but did show an elevated high sensitivity CRP of 4.3 mg/L (n <1.0 mg/L) and a sedimentation rate of 33 mm/hr (n 0—20 mm/hr). A thyroid uptake and scan showed markedly decreased uptake suggestive of thyroiditis. The patient was started on a prednisone taper with improvement in his TFTs. At his follow up visit approximately one month later, he reported increasing stiffness in his bilateral jaw and continuing palpitations with movement despite near normalization in his FT4 and TT3, suggestive of possible underlying cardiac conduction defects. He did not recall a tick bite but lived in an area with endemic Lyme disease. Lyme antibodies were sent and returned with a positive Lyme IgG and an indeterminate Lyme IgM, which would be consistent with an active Lyme disease infection at the time of his initial presentation. Treatment for Lyme disease was prescribed. Conclusion: Between 1991 and 2021, the incidence of Lyme disease in the United States doubled due to the combined effects of climate change, increasing host species populations, and human encroachment on animal habitats. People who live in areas with endemic Lyme disease, such as the Northeast and upper Midwest regions of the United States, are at risk even if they do not recall a specific exposure. Although Lyme thyroiditis is extremely rare, its incidence is expected to increase as the overall incidence of Lyme disease increases. Therefore, it is important to consider Lyme disease in the differential when a patient from an endemic area presents with unexplained thyroiditis. Presentation: 6/2/2024