Nishiyama Kozo, Nakamura Hirotoshi
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine.
Nihon Rinsho. 2002 Feb;60(2):379-84.
Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of thyroid hormone receptor beta gene. RTH is manifested by inappropriately elevated levels of serum thyrotropin in the presence of elevated circulating thyroid hormones. Most of the patients with RTH do not manifest remarkable clinical features, but may represent partial hypothyroidism. Sometimes even tachycardia, sweating, body weight loss or attention-deficit hyperactivity disorder are found. TR beta mutants, which have reduced T3-binding activities and aberrant interactions with transcriptional cofactors, act in a dominant negative fashion against wild type TRs. Although no human disease has been found to be caused by TR alpha gene mutations, TR alpha knockout mice suggest that TR alpha plays a major role in the regulation of heart rate and basal metabolism and TR alpha gene-deficiency does not express the RTH phenotype.
甲状腺激素抵抗（RTH）是一种由甲状腺激素受体β基因突变引起的遗传性疾病。RTH的表现为在循环甲状腺激素升高的情况下，血清促甲状腺激素水平异常升高。大多数RTH患者没有明显的临床特征，但可能表现为部分甲状腺功能减退。有时甚至会出现心动过速、出汗、体重减轻或注意力缺陷多动障碍。TRβ突变体具有降低的T3结合活性和与转录辅因子的异常相互作用，以显性负性方式作用于野生型TRs。虽然尚未发现由TRα基因突变引起的人类疾病，但TRα基因敲除小鼠表明TRα在心率和基础代谢的调节中起主要作用，TRα基因缺陷不会表现出RTH表型。
