Department of Endocrinology, Diabetes & Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Eur Thyroid J. 2024 Nov 20;13(6). doi: 10.1530/ETJ-24-0286. Print 2024 Dec 1.
Patients with an inactive thyroid hormone (TH) transporter MCT8 (Allan-Herndon-Dudley Syndrome, AHDS) display severe neurological impairments and motor disabilities, indicating an indispensable function of MCT8 in facilitating TH access to the human brain. Consequently, the CNS of AHDS patients appears to be in a TH deficient state, which greatly compromises proper neural development and function. Another hallmark of this disease is that patients exhibit elevated serum T3 levels, leading to a hyperthyroid situation in peripheral tissues. Several treatment strategies have been developed and evaluated in preclinical mouse models as well as in patients. Here, we discuss these different therapeutic approaches to overcome MCT8 deficiency and summarize the current achievements and challenges in improving brain maturation in the absence of MCT8.
患有甲状腺激素（TH）转运体 MCT8 功能缺失的患者（Allan-Herndon-Dudley 综合征，AHDS）表现出严重的神经损伤和运动障碍，表明 MCT8 在促进 TH 进入人脑方面具有不可或缺的作用。因此，AHDS 患者的中枢神经系统似乎处于 TH 缺乏状态，这极大地影响了正常的神经发育和功能。该疾病的另一个特征是患者血清 T3 水平升高，导致外周组织出现甲亢。已经在临床前小鼠模型和患者中开发和评估了几种治疗策略。在这里，我们讨论了这些不同的治疗方法来克服 MCT8 缺乏，并总结了在没有 MCT8 的情况下改善大脑成熟度的当前成就和挑战。
