Rovet Joanne F
Department of Paediatrics, University of Toronto, Toronto, ON M5G1X8, Canada.
Neurosciences and Mental Health Program, The Hospital for Sick Children, Toronto, ON M5G0A4, Canada.
J Clin Endocrinol Metab. 2024 Sep 16;109(10):e1950-e1954. doi: 10.1210/clinem/dgae453.
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.
在过去十年中，描述显性甲状腺功能减退症（OH）和亚临床甲状腺功能减退症（SCH）患者的神经认知后遗症以及相关的脑结构和功能异常的文章激增。研究结果表明，主要影响额叶，OH患者的预后通常比SCH患者更差。最近的几项研究还表明，甲状腺功能减退患者的海马体可能较小，而海马体是记忆的关键结构。
张及其同事发表在《临床内分泌与代谢杂志》上的论文采用了两种新颖的方法来分析海马体的结构和功能。一种方法使用自动处理工具将海马体分割成不同的子区域，另一种方法进行连通性分析，以评估特定海马体子区域与皮质区域之间的关系。相对大量的OH和SCH患者以及健康对照者接受了整体认知功能测试，并进行了结构和功能磁共振成像。结果显示，甲状腺功能减退组在记忆量表上的得分显著低于对照组，并且在选择性子区域的海马体体积也较小。SCH组的影响比OH组更强，OH组在海马体子区域与特定额叶区域之间还表现出不同的连通模式。
为了理解这些发现，我查阅了啮齿动物和人类文献中关于甲状腺激素在海马体功能中的作用、海马体亚区及其假定功能和连接的内容。由于目前的结果表明SCH可能代表一种具有独特脑表现的不同临床实体，我对这些发现提出了两种解释，一种涉及脑屏障中的转运体缺陷，另一种涉及血脑屏障血管单元的差异性神经变性。
