Targeting the Manifestations of Subclinical and Overt Hypothyroidism Within the Hippocampus

The past decade has witnessed a surge of articles describing the neurocognitive sequelae and associated structural and functional brain abnormalities of patients with overt hypothyroidism (OH) and subclinical hypothyroidism (SCH). Findings show effects primarily within the frontal lobes with usually worse outcomes for OH than SCH. Several recent studies have also indicated hypothyroid patients may have smaller hippocampi, a key structure for memory.

The JCEM paper by Zhang and colleagues applies 2 novel approaches for analyzing hippocampal structure and function. One uses an automated processing tool that segments the hippocampus into distinct subregions, and the other performs connectivity analysis to assess the relationships between specific hippocampal subregions and cortical areas. Relatively large samples of OH and SCH patients and healthy controls received a test of global cognitive functioning and underwent structural and functional magnetic resonance imaging. Results showed hypothyroid groups scored significantly below controls on the memory scale and also had smaller hippocampal volumes in selective subregions. Effects were stronger for SCH than OH groups, who also showed different patterns of interconnectivity between hippocampal subregions and specific frontal lobe areas.

To make sense of these findings, I explored the rodent and human literatures on thyroid hormone's role in hippocampal functioning and on hippocampal subfields and their purported functions and interconnections. Because current results suggest SCH may represent a distinct clinical entity with unique brain manifestations, I hypothesized 2 explanations for these findings, one involving transporter defects in the brain barriers and the other, differential neurodegeneration of the blood-brain barrier vascular unit.