Structural and Functional Alterations of Hippocampal Subfields in Patients with Adult-onset Primary Hypothyroidism

Abstract Context Hypothyroidism is often associated with cognitive and emotional dysregulation; however, the underlying neuropathological mechanisms remain elusive. Objective The study aimed to characterize abnormal alterations in hippocampal subfield volumes and functional connectivity (FC) in patients with subclinical hypothyroidism (SCH) and overt hypothyroidism (OH). Methods This cross-sectional observational study comprised 47 and 40 patients with newly diagnosed adult-onset primary SCH and OH, respectively, and 53 well-matched healthy controls (HCs). The demographics, clinical variables, and neuropsychological scale scores were collected. Next, the hippocampal subfield volumes and seed-based FC were compared between the groups. Finally, correlation analyses were performed. Results SCH and OH exhibited significant alterations in cognitive and emotional scale scores. Specifically, the volumes of the right granule cell molecular layer of dentate gyrus (GC-ML-DG) head, CA4 and CA3 head were reduced in SCH and OH groups. Moreover, the volumes of the right molecular layer (ML) head, CA1 body, left GC-ML-DG head, and CA4 head were lower in SCH. In addition, the hippocampal subfield volumes decreased more significantly in SCH than OH. The seed-based FC decreased in SCH but increased in OH compared with HCs. Correlation analyses revealed thyroid hormone (TH) was negatively correlated with FC values in hypothyroidism. Conclusions Patients with SCH and OH might be at risk of cognitive decline, anxiety, or depression, and exhibited alterations in the volume and FC in specific hippocampal subfields. Furthermore, the reduction in volume was more pronounced in SCH. This study provides novel insights into the neuropathological mechanisms of brain impairment in hypothyroidism.