甲状腺功能亢进患者甲状腺功能与肺动脉压力相关性研究

发布时间：2018-03-17 23:35

  本文选题：甲状腺功能亢进症　切入点：肺动脉高压　出处：《河北医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:甲状腺功能亢进症(Hyperthyroidism,简称甲亢),是内分泌专业最常见的疾病之一,在普通人群中的患病率达到0.5%,也有报道可达1%,男女患病比例为1:4-6,在女性人群中患病率在2%左右。临床中,依据甲亢发生的病因不同,分为:弥漫性毒性甲状腺肿、结节性毒性甲状腺肿、甲状腺自主高功能腺瘤和碘甲亢。在众多病因导致的甲亢中,毒性弥漫性甲状腺肿(Graves disease,GD)的比例可达85%左右,因GD患病率为最高,发病情况也最为普遍,所以一般意义上的甲亢都指的是GD。近些年来,较多报道都提示了甲状腺功能亢进症与肺动脉高压(Pulmonary hypertension)可以同时合并出现,这种现象,也在内分泌专业医生中,逐渐得到重视。第3次世界卫生组织肺动脉高压专家组会议,在关于肺动脉高压新诊断分类标准中,针对特发性肺动脉高压的病因,明确纳入了甲状腺疾病作为其中一个病因,且称其为“不可忽视的”危险因素。报道中,尤其提到以甲亢合并肺动脉高压的现象最为多见,其病因尚未能完全阐述明确,可能与甲亢导致的高心输出量、高动力循环状态密切相关,也有人推断,甲状腺疾病的发生往往与自身免疫有密切的相关性,甲亢合并肺动脉高压,也可能与自身免疫反应导致的血管内皮损伤,和由此引起的功能紊乱存在相关性。但对于甲亢患者何时发生肺动脉高压,肺动脉压力的变化与甲状腺激素水平有何相关,肺动脉压力变化与甲状腺相关抗体滴度是否相关,国内外尚无相关报道。血浆B型钠尿肽(brain natriuretic peptide,BNP)是反映患者肺动脉压力水平的良好指标,可以用来预测和评估肺动脉高压的发生。本研究拟通过测定不同时期甲亢患者的肺动脉压力、BNP水平、甲状腺相关抗体水平,进一步探讨甲亢患者的肺动脉压力变化特点,了解肺动脉压力水平与甲状腺激素水平之间的联系,分析肺动脉压力与甲状腺抗体水平是否存在关联,以期对甲亢患者肺动脉高压的预防提供佐证。方法:筛选2013年12月至2014年10月就诊于河北省承德市中心医院内分泌科门诊、住院处甲亢患者,进行研究。所有研究对象根据甲状腺功能状态分为三个组:A组(临床甲亢组)30例:年龄18-60岁,TSH0.55 m IU/m L、FT417.6 pg/m L、FT34.2 pg/ml,无心脏病史及其他慢性疾病史;B组(亚临床甲亢组)30例:年龄18-60岁;TSH0.55 m IU/m L、FT3,FT4正常,无心脏病史及其他慢性疾病史;C组(临床缓解组)30例:甲亢经口服药治疗,已进入临床症状缓解期,甲功已完全正常状态,在药物维持期,以相同时期,在承德市中心医院体检中心体检的健康人群30例作为对照组N组。研究对象均取得知情同意后,进行甲状腺功能和相关抗体的检测,同时测定血浆BNP浓度,于我院超声室进行肺动脉压水平检测。血浆BNP浓度检测方法:患者于空腹状态时,抽取静脉血2ml,以依地酸(EDTA)抗凝管留取,立即送检,采用干式快速免疫荧光法定量测定BNP值;检测设备为美国克格仪器有限公司:M368456型号的BNP测试仪,可快速检测,15分钟报告,正常值为0-100pg/ml。肺动脉高压诊断标准参照2009年欧洲心脏病学会(ESC)指南,依据超声心动图测得肺动脉收缩压(PASP)值确定。肺高压诊断标准为静息时经胸超声心动图估测PASP35mm Hg,35≤PASP50mm Hg为轻度,50≤PASP70mm Hg为中度,PASP≥70 mm Hg为重度肺高压。然后进行统计学处理,把各组研究对象间甲状腺激素水平、相关抗体、肺动脉压力、血浆BNP值分别进行比较;进行肺动脉压水平与甲状腺激素水平、相关抗体以及血浆BNP的相关性分析。结果:1研究纳入的120人中,其中对照组:男性7人,女性23人,年龄范围(40.5±15.2)岁;A组:男性8人,女性22人,年龄范围(43.2±16.3)岁;B组:男性6人,女性24人,年龄范围(42.1±15.7)岁;C组:男性7人,女性23人,年龄范围(41.8±14.9)岁。各组间年龄差异无统计学意义(P0.05),各组间性别差异无统计学意义(P0.05),各组间研究对象具有可比较性。2健康对照组人群平均肺动脉压力为24.15mm Hg,肺高压患病率为0%,临床甲亢组患者平均肺动脉压力为48.37mm Hg,肺高压患病率为33%,亚临床甲亢组患者平均肺动脉压力为36.91mm Hg,肺高压患病率为30.0%,临床缓解组患者平均肺动脉压力为34.58mm Hg,肺高压患病率为26.7%,临床甲亢组、亚临床甲亢组和临床缓解组的肺动脉压水平和肺高压患病率,与健康对照组相比,差异显著(P0.05);临床甲亢组较亚临床甲亢组、临床缓解组的肺动脉压水平差异显著(P0.05),亚临床甲亢组、临床缓解组肺动脉压力、肺动脉高压患病率组间比较差异不明显(P0.05)。3肺动脉压力分别与TSH、FT3、FT4、TPOAb、Tg Ab、TRAb进行相关性分析,结果显示肺动脉压力水平与TSH呈轻度负相关(r=-0.452,P0.05),与甲状腺激素水平表现出正相关性,与其他指标无线性相关性(P0.05)。4血浆BNP检测值的比较,临床甲亢组、亚临床甲亢组和临床缓解组的各血浆BNP平均值分别为:317.13pg/ml、298.12 pg/ml、259.41 pg/ml,健康对照组为20.12 pg/ml,相比之下,甲亢患者BNP水平与健康对照组差异显著(P0.05);临床甲亢组、亚临床甲亢组和临床缓解组的血浆BNP值组间比较,差异不明显(P0.05),结果显示肺动脉压力水平与血浆BNP值成中度正相关(r=0.557,P0.05)。结论:甲亢患者肺动脉压力水平和肺动脉高压患病率较正常人群为高,肺动脉高压在亚临床甲亢阶段即可发生,不同时期的甲亢患者肺动脉高压患病率不同,肺动脉压力水平随甲亢的严重程度增高。甲状腺抗体水平并没有表现出与肺动脉高压水平的明显的相关性。肺动脉压力水平与血浆BNP值呈中度正相关性,可用来评估甲亢患者肺动脉高压的发生风险。
[Abstract]:Objective: hyperthyroidism (hyperthyroidism, referred to as Hyperthyroidism) is one of the most common endocrine professional disease in the general population prevalence rate of 0.5%, there are reports of up to 1%, the ratio between men and women was 1:4-6, the prevalence rate of around 2% in women. The clinical and etiology of hyperthyroidism in patients according to the different, divided into: diffuse toxic goiter, nodular toxic goiter, thyroid adenoma and the function of the independent high iodine hyperthyroidism. Resulted in numerous causes of hyperthyroidism, diffuse toxic goiter (Graves disease, GD) the proportion of up to about 85%, due to the prevalence of GD was the highest, the incidence is most common. So the general sense of hyperthyroidism refers to GD. in recent years, many reports have suggested that hyperthyroidism and pulmonary arterial hypertension (Pulmonary hypertension) can also occur, this phenomenon also in endocrinology The doctor, gradually get attention. The third WHO expert pulmonary hypertension group meeting on pulmonary arterial hypertension diagnostic classification standard, according to the etiology of idiopathic pulmonary arterial hypertension, clear into thyroid disease as a cause, and called it "the risk can not be ignored in the report" factors. In particular, to mention hyperthyroidism complicated with pulmonary hypertension is the most common phenomenon, its etiology is still not fully explain clearly, high cardiac output may lead to high power and hyperthyroidism, closely related to the circulating state was also inferred that the thyroid disease often is associated with autoimmune hyperthyroidism complicated with pulmonary hypertension may also lead to vascular endothelial injury, reaction and autoimmune disorders, and the resulting correlation exists. But for the patients with hyperthyroidism when pulmonary hypertension, pulmonary arterial pressure changes What is the level of thyroid hormone and thyroid, and whether the change of pulmonary artery pressure related antibody titer, there is no relevant reports at home and abroad. Plasma B type natriuretic peptide (brain natriuretic, peptide, BNP) is a good indicator to reflect the level of patients with pulmonary arterial pressure, can be used to predict and evaluate the occurrence of pulmonary hypertension. This study through the determination of pulmonary arterial pressure in patients with hyperthyroidism in different periods of BNP level, thyroid related antibody level, to further explore the changes of pulmonary arterial pressure in patients with hyperthyroidism, understanding between pulmonary artery pressure level and thyroid hormone levels, analysis of pulmonary artery pressure and thyroid antibody level is associated, in order to prevent the pulmonary artery in patients with hyperthyroidism the pressure to provide evidence. Methods: from December 2013 to October 2014 screening clinic in Chengde Central Hospital of Hebei province outpatient department of Endocrinology, hospital department of hyperthyroidism All patients were studied. The research object according to the thyroid function was divided into three groups: group A (clinical hyperthyroidism group) 30 cases: age 18-60 years, TSH0.55 m IU/m L, FT417.6 pg/m L, FT34.2 pg/ml, had no history of heart disease and other chronic diseases; group B (subclinical hyperthyroidism group) 30 cases: 18-60 years of age; TSH0.55 m IU/m L, FT3, FT4 normal, no history of heart disease and other chronic diseases; group C (remission group) 30 cases of hyperthyroidism: oral drug treatment, has entered the clinical remission period, thyroid function is completely normal, the maintenance period in medicine, in the same period, in healthy physical examination center of Chengde Central Hospital, 30 cases of group N as the control group. The research object was obtained after informed consent for detection of thyroid function and antibody, simultaneous determination of plasma concentration of BNP in our hospital, Department of ultrasonography for pulmonary arterial pressure level detection method. To detect the concentration of plasma BNP in patients with: The fasting state, venous blood 2ml, with EDTA (EDTA) anticoagulant tube specimens, inspection immediately, quantitative determination of BNP value by fluoroimmunoassay; testing equipment for America's Instrument Co. Ltd.: BNP tester model M368456, rapid detection, 15 minutes report, normal value as the standard pressure 0-100pg/ml. diagnosis of pulmonary artery in reference to the 2009 European Society of Cardiology (ESC) guidelines, according to echocardiography measured pulmonary artery systolic pressure (PASP) values. For the diagnosis of pulmonary hypertension standard resting echocardiography to estimate PASP35mm Hg, 35 PASP50mm Hg 50 PASP70mm Hg for mild, moderate, PASP = 70 mm Hg for severe pulmonary hypertension. Then were statistically related to each research object between the antibody level of thyroid hormone, and pulmonary artery pressure, plasma BNP values were compared; pulmonary artery pressure levels and thyroid hormone levels, resistance 浣撲互鍙婅��娴咮NP鐨勭浉鍏虫，

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