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摘要: 甲状腺激素抵抗综合征(RTH)是甲状腺激素受体(TR)基因突变,导致器官对甲状腺激素(TH)的敏感性降低,TH对全身组织器官作用障碍的一种罕见综合征。THRB基因突变导致的RTH称为β型甲状腺激素抵抗综合征(RTHβ)。RTHβ主要特点是循环血中甲状腺素(T4)升高、三碘甲腺原氨酸(T3)水平正常或升高、促甲状腺激素(TSH)水平正常或轻度升高,临床上RTHβ容易被误诊为甲状腺功能亢进症,予以抗甲状腺药物、放射性131I治疗或手术治疗,进而导致TH抵抗加重,因此对该病的正确诊断非常重要。本文对RTHβ的分子机制、临床特征、诊断及治疗予以归纳并总结。
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关键词:
- 甲状腺激素抵抗综合征 /
- THRB基因突变 /
- 甲状腺激素
Abstract: The syndrome of resistance to thyroid hormone(RTH) is a rare syndrome caused by the mutation of thyroid hormone receptor (TR) gene, which reduces the sensitivity of target organs to thyroid hormone (TH) and leads to the dysfunction of TH. Thyroid hormone resistance syndrome β (RTHβ) is caused by the mutations in the THRB gene. The main characteristics of RTHβ are increased thyroxine (T4) in the circulating blood, normal or elevated levels of triiodothyronine(T3), paired with normal or high thyroid-stimulating hormone (TSH) concentration. Clinically, it is easy to misdiagnose RTHβ as hyperthyroidism, and give anti-thyroid drugs, radioactive 131I therapy or surgery, which then leads to the aggravation of TH resistance, so the correct diagnosis of the disease is critical. In this paper, the molecular mechanism, clinical characteristics, diagnosis and treatment of RTHβ are summarized.-
Key words:
- thyroid hormone resistance syndrome /
- THRB mutations /
- thyroid hormone
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表 1 高甲状腺素血症鉴别诊断
Table 1. Differential diagnosis of hyperthyroxinemia
疾病名称 临床表现 FT4 FT3 TSH rT3 TT4 TT3 基因缺陷 其他 RTHβ 甲状腺肿、窦性心动过速、轻微神经认知功能障碍 ↑ ↑或N ↑或N ↑ ↑ ↑或N THRB 甲状腺摄碘率升高;L-T3抑制试验:TSH部分抑制 RTHα 神经认知功能障碍、身材矮小、骨发育延迟、心率缓慢、巨颅症、便秘、贫血 ↓ ↑或N N ↓ ↓ ↑或N THRA TSH瘤 甲状腺毒症 ↑ ↑ ↑或N ↑ ↑ ↑ 无 α-GSU↑、α-GSU/TSH↑;MRI影像学存在占位病变、TRH兴奋试验阴性、L-T3抑制试验TSH不被抑制 TBG增多症 无 N N N ↑ ↑ ↑ TBG的基因拷贝数异常 血清TBG↑ FDH 无 ↑或N ↑或N N ↑ ↑ ↑或N ALB 化学发光免疫分析法检测FT3或FT4假性升高、平衡透析或超滤后检测FT3、FT4水平正常 THAAb干扰 无 ↑或N ↑或N N N ↑或N ↑或N 无 THAAb阳性 RTHβ:β型甲状腺激素抵抗综合征;RTHα:α型甲状腺激素抵抗综合征;TBG:甲状腺素结合球蛋白;THAAb:甲状腺激素自身抗体;FDH:家族性白蛋白异常高甲状腺素血症;TSH:促甲状腺激素;FT4:游离T4;FT3:游离T3;rT3:反T3;TT4:总T4;TT3:总T3;α-GSU:血清糖蛋白激素α亚单位;TRH:促甲状腺激素释放激素;N:正常;↑:升高;↓:下降 -
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