Engelmann Beatrice, Bischof Julia, Dirk Anne-Luise, Friedrich Nele, Hammer Elke, Thiele Thomas, Führer Dagmar, Homuth Georg, Brabant Georg, Völker Uwe
Interfaculty Institute for Genetics and Functional Genomics, Greifswald, Germany.
Experimental and Clinical Endocrinology, Med Clinic I, University of Lübeck, Lübeck, Germany.
Eur Thyroid J. 2015 Sep;4(Suppl 1):119-24. doi: 10.1159/000381769. Epub 2015 May 28.
Hyperthyroidism is known to induce a hypercoagulable state. It stimulates plasma levels of procoagulative factors and reduces fibrinolytic activity. So far most of the data have been derived from patients with endogenous hyperthyroidism with a wide variability in the underlying pathogenesis and severity of the disease.
In this study we experimentally induced thyrotoxicosis in healthy volunteers to explore the effects of thyroxine excess on the plasma proteome. Using a shotgun proteomics approach, the abundance of plasma proteins was monitored before, during and after thyrotoxicosis.
Sixteen healthy male subjects were sampled at baseline, 4 and 8 weeks under 250 µg/day thyroxine p.o., as well as 4 and 8 weeks after stopping the application. Plasma proteins were analyzed after depletion of 6 high-abundance proteins (MARS6) by LC-ESI-MS/MS mass spectrometry. Mass spectrometric raw data were processed using a label-free, intensity-based workflow. Subsequently, the linear dependence between protein abundances and fT4 levels were calculated using a Pearson correlation.
All subjects developed biochemical thyrotoxicosis, and this effect was reversed within the first 4 weeks of follow-up. None of the volunteers noticed any subjective symptoms. Levels of 10 proteins involved in the coagulation cascade specifically correlated with fT4, supporting an influence of thyroid hormone levels on blood coagulation even at nonpathological levels.
The results suggest that experimental thyrotoxicosis exerts selective and specific thyroxine-induced effects on coagulation markers. Our study design allows assessment of thyroid hormone effects on plasma protein levels without secondary effects of other diseases or therapies.
已知甲状腺功能亢进会导致高凝状态。它会刺激促凝血因子的血浆水平并降低纤溶活性。到目前为止，大多数数据来自内源性甲状腺功能亢进患者，其潜在发病机制和疾病严重程度差异很大。
在本研究中，我们在健康志愿者中实验性诱导甲状腺毒症，以探讨甲状腺素过量对血浆蛋白质组的影响。使用鸟枪法蛋白质组学方法，监测甲状腺毒症发生前、期间和之后血浆蛋白质的丰度。
16名健康男性受试者在基线、口服250μg/天甲状腺素4周和8周时以及停药后4周和8周进行采样。通过LC-ESI-MS/MS质谱法去除6种高丰度蛋白质（MARS6）后分析血浆蛋白质。使用无标记、基于强度的工作流程处理质谱原始数据。随后，使用Pearson相关性计算蛋白质丰度与游离甲状腺素（fT4）水平之间的线性相关性。
所有受试者均出现生化性甲状腺毒症，且这种效应在随访的前4周内逆转。没有志愿者注意到任何主观症状。参与凝血级联反应的10种蛋白质的水平与fT4特异性相关，这支持了即使在非病理水平下甲状腺激素水平对血液凝固的影响。
结果表明，实验性甲状腺毒症对凝血标志物产生选择性和特异性的甲状腺素诱导效应。我们的研究设计允许评估甲状腺激素对血浆蛋白水平的影响，而不受其他疾病或治疗的次要影响。
