Chatterjee V K
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, UK.
Horm Res. 1997;48 Suppl 4:43-6. doi: 10.1159/000191312.
Resistance to thyroid hormone (RTH) is usually dominantly inherited and is characterized by elevated free thyroid hormones in the serum and failure to suppress pituitary thyroid stimulating hormone (TSH) secretion with variable refractoriness to hormone action in peripheral tissues. Two major forms of the disorder are recognized: asymptomatic individuals with generalized resistance (GRTH) and patients with thyrotoxic features, suggesting predominant pituitary resistance (PRTH). Molecular genetic analyses indicate that both GRTH and PRTH are associated with diverse mutations in the thyroid hormone receptor beta gene, which localize to three regions in the hormone binding domain of the receptor. In addition to being functionally impaired, the mutant receptors are also able to inhibit their wild-type counterparts in a dominant negative manner. Recognized features of RTH include failure to thrive, growth retardation and attention-deficit hyperactivity disorder in childhood, and goitre and thyrotoxic cardiac symptoms in adults. The pathogenesis of variable tissue resistance is not fully understood but may be related to the differing tissue distributions of a and b thyroid hormone receptors and variable dominant negative activity of mutant receptors on different target genes.
甲状腺激素抵抗（RTH）通常为显性遗传，其特征是血清中游离甲状腺激素升高，垂体甲状腺刺激激素（TSH）分泌未能被抑制，且外周组织对激素作用存在不同程度的抵抗。该疾病主要有两种类型：具有全身抵抗的无症状个体（GRTH）和具有甲状腺毒症特征的患者，提示主要为垂体抵抗（PRTH）。分子遗传学分析表明，GRTH和PRTH均与甲状腺激素受体β基因的多种突变有关，这些突变位于受体激素结合域的三个区域。除功能受损外，突变受体还能够以显性负性方式抑制其野生型对应物。RTH的公认特征包括儿童期生长发育迟缓、注意力缺陷多动障碍，以及成人期甲状腺肿和甲状腺毒症心脏症状。组织抵抗程度各异的发病机制尚未完全明确，但可能与α和β甲状腺激素受体在不同组织中的分布差异以及突变受体对不同靶基因的显性负性活性不同有关。
