Division of Endocrinology, Erasmus MC, Rotterdam, The Netherlands.
Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
PLoS One. 2018 Apr 12;13(4):e0194259. doi: 10.1371/journal.pone.0194259. eCollection 2018.
Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone.
To study if serum miRNA profiles are changed in different thyroid states.
We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification.
Mean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment.
Although we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans.
甲状腺功能减退症患者的左甲状腺素替代治疗无法使血清和组织中的甲状腺素和三碘甲状腺原氨酸浓度完全恢复生理水平。正常的血清促甲状腺激素（TSH）浓度仅反映垂体甲状腺功能正常，因此需要新的生物标志物来代表组织特异性甲状腺状态。微小 RNA（miRNA）是小的非编码调节 RNA，具有组织特异性表达模式，可在血清中检测到。先前的研究已经证明了在甲状腺激素的影响下组织中 miRNA（前体）的差异表达。
研究不同甲状腺状态下血清 miRNA 谱是否发生改变。
我们研究了 13 名甲状腺功能减退症患者（6 名男性），他们在 TSH 抑制治疗期间和甲状腺激素停药 4 周后接受了治疗。使用磁珠捕获系统从血清中分离出 384 种定义明确的 miRNA。随后，使用 TaqMan 阵列卡 3.0 平台对个体靶标扩增后的 miRNA 进行分析。
研究对象的平均年龄为 44.0 岁（范围 20-61 岁）。在停用左甲状腺素时，中位 TSH 水平为 88.9mU/l，在用左甲状腺素治疗时为 0.006mU/l，中位剂量为 2.1μg/kg。在进行归一化以允许样本间分析后，配对分析显示在停用和使用左甲状腺素治疗时，分析的 384 种 miRNA 中的任何一种的表达均无显著差异。
尽管我们之前在骨骼肌中显示甲状腺功能减退状态下 pri-miRNA 133b 和 206 的表达上调，但本研究并没有提供证据表明甲状腺状态也会影响人类血清中的 miRNA。
