白蛋白R218H突变引起的家族性异常白蛋白高甲状腺素血症
1. 广东省第二人民医院内, 内分泌科内分泌科, 广东广州 510317
2. 前海人寿广州总医院, 内分泌代谢科, 广东广州 511325
| 摘 要： | 家族性异常白蛋白高甲状腺素血症（FDH）容易作为临床甲亢而误诊误治，一般认为其病理意义不大，本研究以一个家系病例为基础，探讨FDH临床表现、遗传特点和基因突变，加深对FDH的认知，以及是否对妊娠有影响。从两例“甲亢”先证者出发并追溯到整个家系，调研其临床病史，进行生化和激素检查、甲状腺相关的功能及影像学检查、TSH分泌动态实验、基因分析。对白蛋白基因分析采用二代高通量测序和Sanger法验证的方法。调查家系中的妊娠史及流产率。先证者为一对有“甲亢”治疗史的父子，其总甲状腺激素明显升高而游离激素仅轻微变化，促甲状腺激素和促甲状腺激素受体抗体正常，同时超声显示甲状腺肿大和血流增加、甲状腺放射性摄取增加，而垂体MRI正常。家系追溯并检测甲功发现在13例直系亲属中有8例为FDH，有4例误诊为“甲亢”并进行过相应治疗，3例参加基因分析均显示白蛋白R218H变异。迄今中国人FDH报道均为R218H变异。R218H相关的FDH有典型的甲状腺激素谱变化、甲状腺激素合成功能增强，呈家系发病，外显率高，有较高的“甲亢”误诊误治概率，不影响妊娠结局。 |
| 关 键 词： | 家族性异常白蛋白高甲状腺素血症; 误诊; 格雷夫斯病; 白蛋白基因 |
| DOI： | 10.57237/j.mrf.2022.01.004 |
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收稿日期: 2022-09-06
接受日期: 2022-10-17
在线出版日期: 2022-12-15
Familial Dysalbuminemic Hyperthyroxinemia Induced by Mutation R218H of Albumin
1. Department of Endocrinology, The Second People’s Hospital of Guangdong Province, Guangzhou 510317, China
2. Department of Endocrinology & Metabolism, Forsea Insurance Guangzhou General Hospital, Guangzhou 511325, China
| Abstract: | Familial Dysalbuminemic Hyperthyroxinemia (FDH) is thought of no clinical significance, but tends to to misdiagnosed and mistreated as Graves’ hyperthyroidism with long time. In a Chinese family to explore clinical characteristics, hereditary features and gene variation of FDH and its effect on pregnancy. Methods: Two propostitus (a father and his son) with hyperthyroidism were re-diagnosed as FDH due to the canonical profile of measured thyroid hormones. After screening thyroid function of the whole family, eight affected of FDH were identified among total thirteen lineal relatives. They were studied in terms of clinical history, biochemical and hormone examination, thyroid imaging and TSH secreting test by dexamethasone and bromocriptine. Three members accepted gene analysis with the next generation sequencing followed by Sanger method. Productive history was investigated in five spouse of the whole family. Results: In the two propostitus, FDH exhibited very high total thyroxine (T4) and mild high total triiodinethyronine (T3), and normal free T4 and T3 besides normal thyroid stimulating hormone (TSH). In addition, ultrasound discovered diffuse goiter and enhanced blood flow, and 99mTc uptake increased, while TSH receptor antibody and pituitary MRI scan remained normal. Other six family members had similar changes of the thyroid hormones and normal TSH which could be suppressed dramatically by dexamethasone and bromocriptine, then were suspected of FDH and thereafter confirmed with gene analysis. Among these eight FDH, four were misdiagnosed with hyperthyroidism and mistakenly received anti-thyroid medication at least one year. Gene analysis of three members revealed R218H variation of albumin gene. Conclusions: R218H associated FDH shows canonical changes of thyroid hormones with increased thyroid function, high penetrance and misdiagnose rate with hyperthyroidism, it exerts no effect on pregnancy. |
| Keywords: | Familial Dysalbuminemic Hyperthyroxinemia; Misdiagnosis; Graves’ Disease; Albumin Gene |
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