Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, United States.
Departments of Medicine, Pediatrics and Committee on Genetics, The University of Chicago, Chicago, IL, United States.
Front Endocrinol (Lausanne). 2021 Mar 31;12:656551. doi: 10.3389/fendo.2021.656551. eCollection 2021.
Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH) and its more common form is caused by mutations in the gene, termed RTHβ. The characteristic biochemical profile is that of elevated serum TH levels in absence of thyrotropin suppression. Although most individuals are considered clinically euthyroid, there is variability in phenotypic manifestation among individuals harboring different mutations and among tissue types in the same individual due in part to differential expression of the mutant TRβ protein. As a result, management is tailored to the specific symptoms of TH excess or deprivation encountered in the affected individual as currently there is no available therapy to fully correct the TRβ defect. This focused review aims to provide a concise update on RTHβ, discuss less well recognized associations with other thyroid disorders, such as thyroid dysgenesis and autoimmune thyroid disease, and summarize existing evidence and controversies regarding the phenotypic variability of the syndrome. Review of management addresses goiter, attention deficit disorder and "foggy brain". Lastly, this work covers emerging areas of interest, such as the relevance of variants of unknown significance and novel data on the epigenetic effect resulting from intrauterine exposure to high TH levels and its transgenerational inheritance.
抗甲状腺激素（RTH）是一种由甲状腺激素（TH）敏感性降低引起的临床综合征，其更为常见的形式是由 基因突变引起的，称为 RTHβ。其特征性生化特征是血清 TH 水平升高而促甲状腺激素不受抑制。尽管大多数个体被认为临床甲状腺功能正常，但由于突变的 TRβ 蛋白的表达存在差异，携带不同 突变的个体之间以及同一个体的不同组织类型之间存在表型表现的可变性。因此，治疗方法根据个体中遇到的 TH 过多或缺乏的具体症状进行定制，因为目前尚无可用的疗法可完全纠正 TRβ 缺陷。本重点综述旨在提供对 RTHβ 的简明更新，讨论与其他甲状腺疾病（如甲状腺发育不全和自身免疫性甲状腺疾病）的不太为人所知的关联，并总结关于该综合征表型变异性的现有证据和争议。对管理的审查涉及甲状腺肿、注意力缺陷障碍和“头脑模糊”。最后，这项工作涵盖了新的研究领域，例如不明意义变异体的相关性以及宫内暴露于高 TH 水平及其跨代遗传的表观遗传效应的新数据。
