Laboratoire de biochimie et biologie moléculaire, CHU Angers, 49933 Angers cedex 9, France; Unité mixte de recherche MITOVASC, CNRS 6015-Inserm U1083, université d'Angers, 49100 Angers, France.
Laboratoire de biochimie et biologie moléculaire, CHU Angers, 49933 Angers cedex 9, France.
Ann Endocrinol (Paris). 2019 Nov;80(5-6):280-285. doi: 10.1016/j.ando.2019.06.005. Epub 2019 Jul 26.
Resistance to thyroid hormones syndrome is defined as increased thyroxine (T4) and triiodothyronine (T3) concentrations associated with normal or sometimes increased thyrotropin (TSH) concentration. This is usually due to a pathogenic variant with loss of function of the gene coding for thyroid hormone receptor β (THRB). This discrepancy in thyroid hormones (TH) and TSH concentrations is also frequently observed in the presence of analytical interference, notably alteration of TH transport proteins in serum. During 2017, 58 samples were sent to our laboratory in the Angers University Hospital Rare Thyroid and Hormone Receptor Disease Reference Center in order to identify an etiology for discrepant TSH and TH results. We sequenced the genes involved in TH regulation, action and transport (THRB,THRA, SECISBP2, SLC16A, ALB, TTR, SERPINA7). Free T4 and free T3 assay were performed with a second immunoassay (Siemens ADVIA Centaur). A genetic cause of discrepancy in TH and TSH concentrations, with mutation in THRB, was found in 26% of cases (15/58). Biological interference due to TH serum transport protein variant was found in 24% (14/58) of cases. No pathogenic variants were found in the other genes studied. Biological interference was also suspected in 26% of cases without genetic variant, in which the biological discrepancy was not confirmed by a second analytical technique (15/58). Finally, no etiology for the biological discrepancy could be found in 24% of cases (14/58). Clinically, patients in whom biological discrepancy was due to analytic interference were more often asymptomatic, and patients with no identified etiology tended to be older. To limit diagnostic errors associated with the finding of discrepant TSH and TH, we recommend initially conducting a second thyroid function test (TSH, free T4 and free T3) with a different assay, and then screening for a genetic variant in gene coding for thyroid hormone receptor β (THRB) and the TH serum transport proteins (ALB, TTR, SERPINA7).
抗甲状腺激素综合征定义为甲状腺素 (T4) 和三碘甲状腺原氨酸 (T3) 浓度升高，同时促甲状腺激素 (TSH) 浓度正常或升高。这种情况通常是由于编码甲状腺激素受体 β (THRB) 的基因突变导致其功能丧失所致。这种甲状腺激素 (TH) 和 TSH 浓度的差异也常发生在分析干扰的情况下，特别是血清中 TH 转运蛋白的改变。2017 年，有 58 个样本被送到昂热大学医院罕见甲状腺和激素受体疾病参考中心，以确定导致 TSH 和 TH 结果不一致的病因。我们对参与 TH 调节、作用和转运的基因（THRB、THRA、SECISBP2、SLC16A、ALB、TTR、SERPINA7）进行了测序。用第二种免疫分析法（西门子 ADVIA Centaur）进行游离 T4 和游离 T3 检测。在 26%的病例（15/58）中发现了 TH 和 TSH 浓度不一致的遗传原因，即 THRB 基因突变。在 24%的病例（14/58）中发现了由于 TH 血清转运蛋白变异引起的生物学干扰。在研究的其他基因中未发现致病性变异。在没有遗传变异的 26%的病例中，也怀疑存在生物学干扰，但通过第二种分析技术并未证实生物学差异（15/58）。最后，在 24%的病例（14/58）中未能找到生物学差异的病因。临床上，由于分析干扰导致生物学差异的患者更常无症状，而未确定病因的患者年龄更大。为了减少与 TSH 和 TH 不一致发现相关的诊断错误，我们建议最初进行第二次甲状腺功能检测（TSH、游离 T4 和游离 T3），使用不同的检测方法，然后筛查甲状腺激素受体 β (THRB) 和 TH 血清转运蛋白（ALB、TTR、SERPINA7）的基因突变。
