RESISTANCE TO THYROID HORMONE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本临床研究的目的是建立和测试临床方案，用于评价最广义定义的甲状腺激素抵抗综合征。甲状腺激素抵抗是终末器官对甲状腺激素反应性降低的综合征。所考虑的条件包括那些生理缺陷，干扰正常量的化学完整的甲状腺激素的生物活性。其中包括：1）甲状腺激素的细胞膜转运功能障碍; 2）甲状腺素原（T_4）转化为活性甲状腺激素（T_3）的功能障碍; 3）甲状腺素受体（TR）引起的T_3的核作用水平障碍。缺陷，被称为经典的甲状腺激素抵抗（RTH）或类似的综合征没有TR？基因突变后者称为nonTR-RTH，被认为与介导甲状腺激素在细胞核作用的辅因子异常有关。这些辅因子被认为是相关核受体所共有的，并且推测它们也可能对糖皮质激素作用产生微妙的抗性。这些缺陷可能是根据甲状腺功能测试怀疑。然而，通常基础甲状腺功能测试不足以做出准确的诊断，并且通常可能需要仔细分析受试者的表型。此外，这些综合征的表型特征将建立基因检测的标准。遗传异常的鉴定可以允许产前诊断和可能的早期干预和治疗。这在与显著神经学后遗症（例如MCT 8突变）相关的缺陷中尤其重要，因为早期干预可能逆转或预防相关发现

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objectives of this clinical investigation are to establish and test clinical protocols that will serve to evaluate syndromes of resistance to thyroid hormone as defined in the broadest sense. Resistance to thyroid hormone are syndromes of reduced end-organ responsivieness to thyroid hormone. Conditions under consideration encompass those physioloigcal defects that interfere with the biological activity of a chemically intact thyroid hormone supplied in normal amount. These include: 1) Abnormalities in cell membrane transport of thyroid hormone; 2) Abnormalities in the conversion of the prohormone 3,3',5,5'-tetraiodothyronine (thyroxine, T4) into the active thyroid hormone, 3,3',5-triiodothyronine (T3) and 3) Abnormalities at the level of nuclear action of T3 due to a TH receptor (TR)? defects, known as the classical resistance to thyroid hormone (RTH) or similar syndromes without TR? gene mutations. The latter, termed nonTR-RTH, are considered to be associated with abnormalities in cofactors mediating the action of thyroid hormone at the nucleus. These cofactors are considered to be common to related nuclear receptors, and it is postulated that they may also produce subtle resistance to glucocorticoid action. These defects may be suspected based on thyroid function tests. However often the basal thyroid function tests are not sufficient to make an accurate diagnosis and often may require a careful analysis of the subject's phenotype. Furthermore characterization of the phenotype of these syndromes would establish criteria for genetic testing. Identification of the genetic abnormality may allow for prenatal diagnosis and possible early intervention and treatment. This would be particularly important in the defects that are associated with significant neurologic sequella (e.g. MCT8 mutations) as early intervention may reverse or prevent the associated findings