Tsunekawa Katsuhiko, Murakami Masami
Rinsho Byori. 2014 Jan;62(1):60-6.
Hormone receptor abnormality is a syndrome of an abnormal mechanism caused by defective receptor function in hormone action. Resistance to thyroid hormone is a syndrome in which the responsiveness of the target organ to thyroid hormone is reduced. Resistance to thyroid hormone exhibits unsuppressed thyrotropin(TSH) despite elevated free thyroxin (FT4) and free 3,5,3'-triiodothyronine (FT3), termed the syndrome of the inappropriate secretion of TSH (SITSH). Resistance to thyroid hormone is mainly caused by a mutation in the thyroid hormone receptor beta (TRbeta) gene. Genetic analysis of the TRbeta gene is important to diagnose resistance to thyroid hormone. TSH receptor (TSHR) abnormality is classified as a gain-of-function mutation and loss-of-function mutation. Loss-of-function mutations in the TSHR gene occur as TSH resistance, which is found to have euthyroid hyperthyrotropinemia or hypothyroidism because of the reduced responsiveness of the receptor to TSH. R450H mutation in the TSHR gene is occasionally observed in Japanese patients with TSH resistance. In Japan, it is suggested that analysis of the R450H mutation in the TSHR gene is useful to determine the cause of hyperthyrotropinemia or hypothyroidism.
激素受体异常是一种因激素作用中受体功能缺陷导致机制异常的综合征。甲状腺激素抵抗是一种靶器官对甲状腺激素反应性降低的综合征。尽管游离甲状腺素（FT4）和游离三碘甲状腺原氨酸（FT3）升高，但甲状腺激素抵抗仍表现为促甲状腺激素（TSH）未被抑制，称为不适当TSH分泌综合征（SITSH）。甲状腺激素抵抗主要由甲状腺激素受体β（TRβ）基因突变引起。TRβ基因的基因分析对诊断甲状腺激素抵抗很重要。TSH受体（TSHR）异常分为功能获得性突变和功能丧失性突变。TSHR基因的功能丧失性突变表现为TSH抵抗，由于受体对TSH的反应性降低，可出现甲状腺功能正常的高促甲状腺素血症或甲状腺功能减退。TSHR基因的R450H突变在日本TSH抵抗患者中偶尔可见。在日本，提示对TSHR基因的R450H突变进行分析有助于确定高促甲状腺素血症或甲状腺功能减退的病因。
