Nagasaki Toshiki, Inaba Masaaki, Henmi Yasuko, Kumeda Yasuro, Ueda Misako, Tahara Hideki, Ishimura Eiji, Onoda Naoyoshi, Ishikawa Tetsuro, Nishizawa Yoshiki
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Eur J Endocrinol. 2004 Feb;150(2):125-31. doi: 10.1530/eje.0.1500125.
This study examined whether levothyroxine (L-T4) replacement might affect serum markers of endothelium injury, including von Willebrand factor (vWF), factor VIII activity and thrombomodulin (TM), during normalization of increased intima-media thickness (IMT) in the common carotid artery (CCA) in hypothyroid patients after L-T4 replacement therapy.
Thirty-three hypothyroid patients were examined for vWF, factor VIII, TM and CCA IMT before and after 1 year of normalization of thyroid function by L-T4 replacement. CCA IMT was measured from digitized still images taken during scanning by high-resolution ultrasonography as an indicator of early atherosclerosis.
Serum factor VIII and vWF increased significantly during 1 year of normalization of thyroid function (from 122.7+/-9.4 to 151.3+/-18.8% (P<0.05) and from 109.9+/-9.6 to 135.2+/-12.4% (P<0.005) respectively), although these values all fell within the respective normal range. Serum TM, in contrast, did not change appreciably in response to L-T4 treatment, moving from 2.57+/-0.15 to 2.74+/-0.18 ng/ml (P=0.086). During 1 year of a euthyroid state, all patients showed a significant decrease in CCA IMT (P<0.0001). Change in serum vWF, but not in factor VIII or TM, showed a positive correlation with that of CCA IMT during L-T4 replacement therapy. Furthermore, the change in serum vWF was significantly and independently associated with change in CCA IMT (r=0.490, P=0.0038).
The present study demonstrated that the improvement of CCA IMT during L-T4 treatment might have the potential to attenuate an elevation of vWF and to attenuate vascular injury by the cardiovascular effects of thyroid hormone in hypothyroid patients.
本研究旨在探讨在甲状腺功能减退患者接受左甲状腺素(L-T4)替代治疗使颈总动脉(CCA)内膜中层厚度(IMT)增加恢复正常的过程中,L-T4替代治疗是否会影响内皮损伤的血清标志物,包括血管性血友病因子(vWF)、凝血因子VIII活性和血栓调节蛋白(TM)。
33例甲状腺功能减退患者在接受L-T4替代治疗使甲状腺功能恢复正常1年前后,检测其vWF、凝血因子VIII、TM及CCA IMT。通过高分辨率超声扫描采集数字化静态图像测量CCA IMT,作为早期动脉粥样硬化的指标。
在甲状腺功能恢复正常的1年期间,血清凝血因子VIII和vWF显著升高(分别从122.7±9.4升至151.3±18.8%(P<0.05)和从109.9±9.6升至135.2±12.4%(P<0.005)),尽管这些值均在各自的正常范围内。相比之下,血清TM对L-T4治疗反应不明显,从2.57±0.15 ng/ml升至2.74±0.18 ng/ml(P=0.086)。在甲状腺功能正常的1年期间,所有患者的CCA IMT均显著降低(P<0.0001)。在L-T4替代治疗期间,血清vWF的变化与CCA IMT的变化呈正相关,而凝血因子VIII或TM的变化则不然。此外,血清vWF的变化与CCA IMT的变化显著且独立相关(r=0.490,P=0.0038)。
本研究表明,L-T4治疗期间CCA IMT的改善可能有潜力减轻vWF的升高,并通过甲状腺激素对甲状腺功能减退患者的心血管作用减轻血管损伤。