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Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the destruction of thyroid follicular cells by thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), leading to hypothyroidism. Hashimoto's encephalopathy (HE) is associated with elevated levels of antithyroid antibodies. An important question is whether brain alterations precede the development of HE and are present in euthyroid patients with HT, and what pathomechanisms could be responsible for these changes. A PubMed search was conducted to identify studies addressing this issue. Numerous questionnaire studies confirmed impairments in cognitive functioning, mental and physical health, and overall well-being in euthyroid HT patients. Additionally, some imaging and mouse model studies indicate that euthyroid patients with HT likely have central nervous system alterations. Antibodies may be involved in the development of these changes. Some research suggests the role of TPOAb and TgAb, while other studies highlight the involvement of coexisting antibodies. Determining whether antibodies are assessed in serum or cerebrospinal fluid (CSF) is crucial. Antibody-specific indices (ASIs) can differentiate between antibodies passively diffusing from the serum and brain-derived antibodies, and could serve as biomarkers for brain alterations in HT patients. Much more research is needed to identify reliable biomarkers and treatments that could improve the quality of life for these patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)