Effect Of L-thyroxine On Serum8-iso-prostaglandin F2α Content In Patlents With Subclinical Hypothyroidism

BackgroundIn recent years, the potential hazards of subclinical hypothyroidism to human have been confirmed by many studies, as an independent risk factor for cardiovascular events, it has been regarded to more and more people. Subclinical hypothyroidism can not only progressed to clinical hypothyroidism, but also suffered abnormal lipid metabolism, in recent years, most research shows that subclinical hypothyroidism can increase the incidence of atherosclerosis, but the specific mechanism is still unclear. Most of the research shows that subclinical hypothyroidism may contribute to vascular endothelial injury、abnormal lipid metabolism and the activation of clotting factors, these mechanisms can accelerate the development of atherosclerosis. Early treatment with L-T4can improve the abnormal lipid metabolism due to subclinical hypothyroidism, but it have not theoretical support about treatment with L-T4can reduce the risk of coronary atherosclerosis and ischemic heart disease.The vitro tests confirmed that the TSH could stimulated the release of arachidonic acid metabolites. Arachidonic acid is the precursor of much biologically active substance, If there is stimulate on the cell membrane, arachidonic acid can be released from the lipid bilayer and formation to hundreds of different biological activity of derivatives, including isoprostanes.8-iso-prostaglandin F2α(8-isoPGF2α) is a new product of isoprostanes discovered in recent years. It was produced by oxidative injury to bio-membrane lipids.8-isoPGF2α is the main component of the isoprostanes, widely exits plasma and tissue.lt is sensitive and specific indicator of oxdative stress.8-isoPGF2α can participated in the form of atherosclerosis by augmented contraction of the human isolated coronary artery-. induced egulate smooth muscle cell differentiation and proliferation and augmented the endothelial cell differentiation to participate in the form of atherosclerosis.8-isoPGF2α is greatly elevated in the cardiovascular diseases such as coronary heart disease. In order to investigate the oxidative stress situation in the early stage of SCH, we analyzed the plasma level of8-isoPGF2α and the effect of levothyroxine on it, we can know the influence of levothyroxine on the oxidative injury in the SCH and we may evaluate the merit of early statin treatment in the SCH patients.ObjectiveIn our study, we evaluated the effect of L-thyroxine replacement therapy to oxidative stress status in SCH patients by detecting serum levels of8-isoPGF2α and investigated the clinical value in replacement therapy of SCH disease and prevent complications.Subjects and methodsData was obtained from an epidemiological investigation of subclinical hypothyroidism in one central community ((Ning yang, Shandong) on January2013. SCH was diagnosed on the basis of elevated TSH>4.2mIU/L with normal FT4and FT3levels. According to the study criteria,35subclinical hypothyroidism and22healthy controls were included in the study. Patients in subclinical hypothyroidism group were treated with L-thyroxine therapy every day. The dose depending on the severity of the disease. The course of treatment was12weeks. Clinical and biological details were obtained by detecting the serum levels of lipid profile and thyroid profile after sample collection, The concentration of oxidative stress parameter8-iso-prostaglandin F2α was obtained with ELISA. SPSS-PC17.0(Statistical package for the social sciences, SPSS Inc, Chicago, IL, USA)for MS Windows was used for statistical analyses. All continuous variables data were presented as mean+SD. Independent-samples t test was used for comparison between SCH and healthy control group. The parameters before and12weeks after treatment were compared in SCH for the evaluation of efficacy of L-thyroxine therapy. Statistical analysis was done with pair-sample t test. Multiple linear regression analysis were used to determine the correlation between the levels of8-iso-prostaglandin F2α,serum thyroid hormone and seum lipid. p values<0.05were considered statistically significant.ResultsThere was no difference in age、sex distribution BMI、blood pressure、FBG between SCH and healthy control group. The plasma levels of TC in the SCH group was higher (p value<0.05) than healthy control group. Levels of TG in SCH group was obviously higher (p value<0.01) than healthy control group. TSH and8-isoPGF2α were significantly increased (p value<0.001) in patients with SCH whereas LDL-、HDL-C、non-HDL-C、FT3、FT4levels were not changed significantly (p value>0.05)in this patients as compared with healthy control. In SCH, the levels of LDL-C was much decreased (p value<0.05) and the levels of FT3and HDL-C were obviously decreased (p value<0.01) and TC、non-HDL-C、TSH、8-isoPGF2α were decreased significantly (p value<0.001), FT4was significantly increased (p value<0.001) after12weeks L-thyroxine treatment, whereas TG was not changed significantly (p value>0.05). The multiple linear regression analysis showed changes in serum TSH and TG levels predicted changes in serum8-isoPGF2α levels in SCH group.Conclusion1.The levels of blood lipid and oxidative stress was higher in SCH group than healthy control group.2.The levels of blood lipid and oxidative stress was improved after L-T4replacement therapy in SCH patients.3.L-T4can reduce serum level of oxidative stress by TSH and TG in SCH patients.