Abstract Disclosure: H. Mejia: None. S.A. Gillis Funderburk: None. S.R. Thomas: None. Background: Subacute thyroiditis (SAT) has been reported following SARS-COV-2 viral infection, as well as in recipients of the mRNA vaccines for SARS-COV-2. Patients present with palpitations, tremors and weight loss as well as low grade fevers and a tender thyroid. It is a self-limited condition that typically follows a triphasic course that may include thyrotoxicosis, hypothyroidism and return to normal thyroid function. Clinical features and sonographic findings can provide a specific diagnosis, and a radioactive iodine uptake study is often not required. Report: In 2021, 123 patients were referred to our outpatient service for evaluation of thyrotoxicosis. Among them, we identified 9 women without history of thyroid disease who presented with clinical findings of SAT with thyrotoxicosis. Patients with history of thyroid dysfunction and thyroid nodules were excluded. The symptoms began between 4-27 days after the first or second dose of either the Pfizer Bio-NTech or the Moderna COVID-19 mRNA vaccine. All tested negative for TSI and had no nodules on ultrasound. 2 patients had thyroid uptake scans which confirmed thyroiditis. All 9 patients improved with symptomatic treatment and thyroid functions normalized with time. Discussion: Since the mRNA vaccines for SARS-COV-2 became nationally available, several adverse reactions have been reported including SAT. The mechanism for post-vaccination SAT or thyroid dysfunction remains unknown. Transmembrane protease serine-2 (TMPRSS-2) and ACE-2 receptors allow the SARS-CoV-2 to enter human cells. ACE-2 and TMPRSS-2 are expressed in thyroid follicular cells, and their expression is higher than in lung cells, especially in women. These situations may explain why SARS-CoV-2 causes SAT in women more frequently. Inactive virus vaccines contain many proteins belonging to the pathogen virus and similar antigenic parts. The increased affinity of the SARS-CoV-2 towards the thyroid suggests that inactive vaccine may also affect the thyroid tissue. In the past, SAT has been reported after an inactive virus vaccine- seasonal influenza vaccine, H1N1 vaccine and hepatitis B vaccine. In addition, the COVID-19 vaccine contains aluminum hydroxide as an adjuvant. Autoimmune inflammatory syndrome induced by adjuvants (ASIA syndrome) was previously reported following various vaccines. A recent article describes a patient with COVID-19 vaccine related ASIA syndrome and SAT. In some cases, elevated proinflammatory markers and cytokines after receiving the vaccine may play a major role, as it can stimulate a significant response from our immune system. Hence, SAT should be included as a possible side effect of receiving these vaccines. Conclusion: Our case series highlights a possible relationship between the COVID-19 mRNA vaccines and subacute thyroiditis which has been previously underreported or not recognized by healthcare providers. Presentation: Friday, June 16, 2023