甲状腺功能与血脂相关性的临床研究
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摘要
甲状腺激素(TH)是人体内最重要的激素之一,对糖、蛋白质、脂肪等物质代谢均有影响。其中,甲状腺激素与脂代谢的关系是近年来研究的重点。TH对脂质代谢的影响涉及合成、动员、分解等多个方面,且其调控机制极为复杂。甲状腺功能减退症是临床上引起血脂异常的重要原因,其中最常见的是高胆固醇血症。同时,甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、脂蛋白(a)等也会发生相应变化。近年来,亚临床甲状腺功能减退症与血脂异常的关系也引起人们的关注。一些研究显示,亚临床甲减同样可以引起血脂发生更易于引起动脉粥样硬化的改变,且由于亚临床甲减发病率较高,因此关于亚临床甲减与心血管疾病的关系也受到越来越多的重视。而随着2型糖尿病患病率的逐年增加和2型糖尿病患者合并较高的血脂异常发生率,对于2型糖尿病患者中合并亚临床甲减及其甲状腺功能与血脂异常的关系也成为摆在临床医生面前的新问题。对于以上种种问题,目前国内尚缺乏临床方面较大样本的系统研究。
目的：1、研究不同甲状腺功能状态下血脂谱、血糖、尿酸的状况,并分析FT3、FT4、TSH等与血脂、血糖、尿酸的相关性。2、分析亚临床甲减患者TSH与血脂间的相关性。3、研究2型糖尿病患者中甲功正常者和合并亚临床甲减者甲状腺功能与血脂间的相关性。
资料与方法：
1、研究对象：(1)收集2007年12月至2009年6月在山东省立医院内分泌科门诊及病房就诊的患者439名,分为甲亢组、亚临床甲亢组、甲减组、亚临床甲减组。并收集同期在我科门诊或病房检查甲状腺功能正常者79例作为对照组。以上入组者均排除肝病、肾病、恶性肿瘤、糖尿病等引起继发性血脂异常的疾病,均为非吸烟者或既往有吸烟史但已戒烟6个月以上,且近3个月内未服用过影响血脂和甲功的药物。(2)将上述患者中的亚临床甲减组与对照组共198例对TSH分层后进行进一步分析。(3)收集2007年12月至2009年6月在我科病房住院治疗的无甲状腺疾病史的2型糖尿病患者102名,检测其甲状腺功能,并按其甲状腺功能分为糖尿病合并亚临床甲减组和糖尿病甲功正常组,并以同期在我科门诊或病房检查甲状腺功能正常且无糖尿病者79例作为对照组。
2、检测指标：患者正常饮食情况下,于夜间12时后禁食,次晨空腹抽取静脉血5m1分装入2个试管,即刻分离血清。一份用于检测甲状腺功能,包括TSH、FT3、FT4、TGAb和TPOAb。另一份检测血清TC、TG、HDL-C、LDL-C、ApoA、ApoB、Lp(a)、血糖、尿酸等指标。
3、统计学方法：因TSH不服从正态分布,故对其进行对数转换后进行分析。各组数值型变量用X±S表示,组间血脂谱、血糖、尿酸比较应用单因素方差分析,两两比较采用q检验。采用Pearson相关及多元回归分析FT3、FT4、TSH等与血脂各指标、血糖、尿酸之间的相关性。上述统计分析均采用SPSS17.0软件包,以P<0.05为差异有统计学意义。
结果：
1、一般资料比较
(1)甲亢组256例(女167例),年龄39.85±12.42岁,BMI 21.71±2.96 kg/m2,亚临床甲亢组12例(女8例),年龄27.33±3.79岁,BMI 22.45±1.40 kg/m2,甲减组52例(女35例),年龄49.45±15.57岁,BMI 25.55±1.99 kg/m2,亚临床甲减组119例(女72例),年龄50.10±11.40岁,BMI 24.44±3.22kg/m2,对照组79例(女50例),年龄41.39±21.07岁,BMI 22.24±4.41kg/m2。各组间性别分布无明显差异,但甲减组和亚临床甲减组较对照组年龄大(P<0.005),而甲亢组和亚临床甲亢组与对照组无明显差异,各组BMI差异亦有显著性,甲减组、亚临床甲减组明显高于甲亢组和对照组(P<0.05)。(2)亚临床甲减组和对照组一般资料比较同(1)。(3)糖尿病亚临床甲减组患者12例(女9例),年龄45.67±16.07岁,BMI 27.24±4.24 kg/m2,糖尿病甲功正常组患者90例(女42例),年龄55.40±13.30岁,BMI 25.73±4.38 kg/m2。对照组资料同前。三组间性别无明显差异,糖尿病甲功正常组年龄较对照组年龄大(P<0.001),糖尿病甲功正常组和糖尿病亚临床甲减组BMI均高于对照组(P<0.05)。
2、甲状腺功能比较
(1)各组间FT3、FT4、TSH、TGAb和TPOAb均有显著差异(P均<0.002)。两两比较发现,甲亢组FT3、FT4明显高于亚临床甲亢组、甲减组、亚临床甲减组和对照组(P均<0.005),甲减组、亚临床甲减组TSH明显高于甲亢组、亚临床甲亢组和正常对照组(P均<0.005),甲亢组TGAb明显低于甲减组(P=0.017),但略高于对照组(P=0.049),甲减组TGAb明显高于亚临床甲减组和对照组(P=0.014、0.001),甲亢组、亚临床甲亢组、甲减组、亚临床甲减组TPOAb均明显高于对照组(P均<0.002)。(2)亚临床甲减组仅TSH和TPOAb明显高于对照组(P均<0.005),余指标与对照组无明显差别。(3)糖尿病并亚临床甲减组和糖尿病甲功正常组及对照组相比,TSH、TGA、TPOAb均有明显差异。两两比较发现,糖尿病亚临床甲减组与对照组相比,TSH、TGAb和TPOAb均有显著升高(P<0.002),而FT3、FT4无明显差异(P>0.05)；糖尿病甲功正常组与对照组比较,除TGAb低于对照组(P=0.005)外,FT4、TSH、TPOAb差异均不明显(P>0.05)；糖尿病亚临床甲减组与糖尿病甲功正常组比较,除FT3无差异外,余指标均有明显差异(P≤0.001)。
3、各组血脂比较
(1)单因素方差分析显示,TC、TG、HDL-C、LDL-C、ApoB在各组之间有显著性差异(P均<0.01),ApoA、Lp(a)、GLU、UA各组间无显著性差异(P>0.05)。两两比较显示,甲亢组TC明显低于对照组(P<0.001),而甲减组和亚临床甲减组则明显高于对照组(P<0.001,0.003)；甲亢组和亚临床甲亢组TG均明显低于对照组(P均<0.001)；HDL-C在甲亢组和甲减组均低于对照组(P=0.001,0.017);甲亢组LDL-C明显低于对照组(P=0.009),而甲减组和亚临床甲减组均明显高于对照组(P均<0.001);ApoA、Lp(a)和血糖在各组无明显差别；ApoB在甲亢组低于对照组(P<0.001),而甲减和亚临床甲减组高于对照组(P<0.001,0.008);UA在甲亢组和亚临床甲减组均高于对照组(P=0.004,0.031)。经年龄、性别和BMI校正后,TC、LDL-C、ApoB仍有显著性差异。
(2)将TSH分层后进行分析发现,在4.2-1OμIU/ml和>10μIU/ml组,TC均明显高于对照组(P分别为0.012和<0.001),而TG在三组间无明显差异。分层分析同时显示,TSH>10μIU/ml组,TC升高率也明显高于对照组(P<0.001),而TSH在4.2-10μIU/ml组TC升高率与对照组相比有升高趋势,但无统计学差异。对年龄进行分层后发现,仅在年龄<20岁组中,TG在亚临床甲减组明显高于对照组(P=0.014),而在其他年龄组中,TC和TG在亚临床甲减组较对照组有升高趋势,但无统计学意义。而在40-60岁年龄组,TG在对照组较亚临床甲减组略高,亦无统计学差异；分性别进行分析显示,亚临床甲减组男性的TC和TG均明显高于对照组(P<0.01),而在女性,亚临床甲减组的TC明显高于对照组(P=0.02),TG两组无明显差异；对BMI进行分层后的分析显示,仅在BMI<24kg/m2亚组中,亚临床甲减组的TC明显高于对照组(P=0.021),其他各亚组中亚临床甲减组的TC较对照组均有升高趋势,但无统计学差异。TG在各亚组中两组比较均无统计学差异。
(3)三组比较,除HDL-C外,其他指标均有显著差异。两两比较发现,无论是糖尿病亚临床甲减组与对照组比较,还是糖尿病甲功正常组与对照组比较,TC、TG、LDL-C、ApoA、ApoB、Lp(a)、GLU、UA均有显著差异(P均<0.001)；而糖尿病亚临床甲减组与糖尿病甲功正常组比较,各项指标均无明显差异。
4、各组Pearson相关和多元线性回归分析结果
(1)经年龄、性别和BMI校正后,各组中血脂与甲功的关系如下所示：甲亢组：LnTSH与Lp(a)显著正相关,FT4与TC、HDL-C、LDL-C和Lp(a)显著负相关,FT3与TC、HDL-C、LDL-C、ApoB、Lp(a)显著负相关；甲减组：LnTSH与TC、HDL-C、LDL-C显著正相关,FT4与HDL-C显著负相关,FT3与上述指标无明显相关；亚临床甲减组：LnTSH与TC显著正相关,FT3与TC显著负相关；在正常甲功组和亚临床甲亢组,FT3、FT4、TSH与血脂、血糖、尿酸均无明显相关性。多元线性回归分析显示,甲亢组FT4可作为TC、HDL-C、LDL-C的预测变量,亚临床甲亢组因例数较少,未做分析；甲减组LnTSH可作为TC、HDL-C的预测变量,FT3可作为TG的预测变量,亚临床甲减组LnTSH可作为TC的预测变量,FT3、FT4均不能作为血脂的预测变量。(2)分析结果见(1)。
(3)FT3、FT4、LnTSH与TC、TG、HDL-C、LDL-C、ApoA、ApoB、Lp(a)、UA等均无显著相关。经年龄、性别和BMI校正后,FT3、FT4、LnTSH与血脂、尿酸仍无相关性。如分组来看,则在糖尿病亚临床甲减组,甲功与血脂、血糖均无相关性,而糖尿病甲功正常组,LnTSH与HDL-C和UA呈显著正相关(P=0.029和0.028)。多元线性回归分析显示,在糖尿病亚临床甲减组和糖尿病甲功正常组LnTSH、FT3、FT4均不能作为血脂各成分的预测变量。
结论：1、甲亢组T、TG、HDL-C、LDL-C、ApoB均明显低于对照组,亚临床甲亢组仅TG低于对照组,甲减组TC、LDL-C、ApoB均高于对照组,HDL-C低于对照组,而亚临床甲减组TC、LDL-C、ApoB、UA高于对照组,ApoA、Lp(a)和血糖在各组无明显差别。经年龄、性别和BMI校正后,TC、LDL-C、ApoB仍有显著性差异。
2、对亚临床甲减组的分析显示,在TSH4.2-10μIU/ml和>10μIU/ml组,TC均明显高于对照组,而TG在三组之间无显著差异。TSH>10μIU/ml组的TC升高率也明显高于对照组,而TSH在4.2-10μIU/ml组TC升高率与对照组相比有升高趋势,但无统计学差异。
3、在年龄<20岁组中,TG在亚临床甲减组明显高于对照组,而在其他年龄组中,TC和TG在亚临床甲减组较对照组有升高趋势,但无统计学意义；亚临床甲减组男性的TC和TG均明显高于对照组,而在女性,亚临床甲减组的TC明显高于对照组,TG两组无明显差异；在BMI<24kg/m2亚组中,亚临床甲减组的TC明显高于对照组,其他各亚组中亚临床甲减组的TC较对照组均有升高趋势,但无统计学差异。TG在各亚组中两组比较均无统计学差异。
4、无论是糖尿病亚临床甲减组与对照组比较,还是糖尿病甲功正常组与对照组比较,除HDL-C外的血脂谱、GLU、UA均有显著差异；而糖尿病亚临床甲减组与糖尿病甲功正常组比较,各项指标均无明显差异。
5、相关及回归分析显示,甲功与血脂中的TC、LDL-C和ApoB密切相关,尤其是TSH与血脂关系更为密切。但在合并糖尿病的患者中FT3、FT4和TSH与血脂的相关性均不明显。
Thyroid hormone (TH) is one of the most important hormone in human body because it influences metabolism of carbohydrate, protein and lipids. And the relation between TH and lipid metabolism was research focus during recent years. TH may has impact on lipid from many aspects including synthesis, mobilization and catabolism, etc, and the regulation mechanism is very complex. Hypothyroidism is an important reason for dyslipidemia clinically. High cholesterol is the most common phenomenon, and triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and lipoprotein(a) will change accordingly. Relation between subclinical hypothyroid and dyslipidemia also leads to attention recently. Some research indicated that serum lipid would change to the direction which more likely to cause atherosclerosis. People may pay more attention to the relation of subclinical hypothyroidism and cardiovascular disease for the reason of high prevanlecce of these two diseases. At the same time, prevalence of type 2 diabetes mellitus become higher and higher, and dyslipidemia is very common among these patients, so the relation between thyroid function and serum lipid in type 2 diabetes also becomes a new problem. And there's still no big sample and systematic clinical research about those questions in our country.
Objective:1. To study changes of serum lipid, glucose and uric acid under different thyroid function, and analyse correlation among FT3、FT4、TSH and serum lipid, glucose and uric acid.2. To study correlation between TSH and lipid in subclinical hypothyroid group.3. To explore relationship of thyroid function and serum lipid in type 2 diabetes mellitus with subclinical hypothyroidism and with normal thyroid function.
Material and methods:
1. Subjects:(1) This cross-sectional study includes 439 subjects whose thyroid function tests revealed abnormal results who were out-patients and in-patients at endocrinology department in Shandong Provincial Hospital, and were devided into four groups including hyperthyroid group, subclinical hyperthyroid group, hypothyroid group and subclinical hypothyroid group by their thyroid function status. And we also collected 79 cases with normal thyroid function as control group. Those with liver function abnormality, abnormal renal function, malignant tumor, diabetes mellitus and diseases which may cause dyslipidemia were exclude. They didn't smoke or prohibit smoking for at least 6 months and they didn't use any drugs which may affect serum lipid and thyroid function for the recent 3 months. (2) We analyzed 198 subjects in subclinical group and control group after TSH graded. (3) 102 diabetic subjects without thyroid disease history were collected who were in-patients at endocrinology department in Shandong Provincial Hospital, and were divided into two groups by thyoid function which were diabetes with subclinical hypothyroid and diabetes with normal thyroid function, and we also collected 79 cases with normal thyroid function as control group.
2. Detected index:Fasting venous blood samples were obtained under normal dietary, and the samples were divided into 2 tubes, and seperated serum immediately. One for detection of thyroid function, including TSH、FT3、FT4、TGAb和TPOAb, and another for TC、TG、HDL-C、LDL-C、ApoA、ApoB、Lp(a)、glucose and uric acid.
3. Statistical analysis:TSH was log transferred for the reason that it didn't obey normal distribution at first. Numeric data were expressed as X±S, one-way ANOVA test was used for comparison means among groups. And post-hoc analysis (LSD method) was used for comparison between each group. Pearson correlation, partial correlation and multiple linear regression analyses were used to determine the correlation between the levels of serum thyroid hormone, serum lipid, glucose and uric acid. SPSS-PC 17.0 (Statistical package for the social sciences, SPSS Inc., Chicago, IL, USA) for MS Windows was used for statistical analyses. P values<0.05 were considered statistically significant.
Results:
1. Comparation of general data (1) 256 cases in hyperthyroid group (167 female),39.85±12.42y old, BMI 21.71±2.96 kg/m2.12 cases in subclinical hyperthyroid group (8 female), 27.33±3.79y old, BMI 22.45±1.40 kg/m2,52 cases in hypothyroid group (35 female), 49.45±15.57y old, BMI 25.55±1.99 kg/m2,119 cases in subclinical hypothyroid group (72 female),50.10±11.40y old, BMI 24.44±3.22kg/m2,79 cases in control group (50 female),41.39±21.07y old, BMI 22.24±4.41 kg/m2. There was no difference in sex distribution, but age in hypothyroid and subclinical hypothyroid group were older than others(P<0.005), and which in hyperthyroid and subclinical hyperthyroid group were same as control group. BMI had difference between groups, which in hypothyroid and subclinical hypothyroid group were higher than control group (P<0.05). (2) Comparation of general data between subclinical hypothyroid and control group see (1). (3) Type 2 diabetes mellitus with subclinical hypothyroid group 12(female 9),45.67±16.07y old, BMI 27.24±4.24 kg/m2, type 2 diabetes mellitus with normal thyroid function 90(42 female),55.40±13.30y old, BMI 25.73±4.38 kg/m2. Data of control group was same as former. Ages in T2DM with normal thyroid function was older than control group(P<0.001), and BMI in T2DM with SCH and normal thyroid function were higher than control group(P<0.05).
2. Comparation of thyroid function (1) FT3, FT4, TSH, TGAb and TPOAb had significant difference in groups. FT3, FT4 were higher in hyperthyroid group than subclinical hyperthyroid group, hypothyroid group, SCH group and control group(all P<0.005), TSH in hypothyroid group and SCH group were higher than hyperthyroid, subclinical hyperthyroid group and control group(all P<0.005), TGAb was lower in hyperthyroid group than hypothyroid group(P=0.017) but a little higher than control group(P=0.049), TGAb in hypothyroid group was much higher than SCH and control group(P=0.014、0.001), TPOAb in hyperthyroid, subclinical hyperthyroid, hypothyroid and SCH group were all much higher than control group(all P<0.002).(2) TSH and TPOAb in SCH group were higher than control group, and other indexes had no significant difference. (3)TSH, TGAb and TPOAb were significant different when compared T2DM with SCH group with T2DM with normal thyroid function group and control group.(P<0.002), FT3, FT4 had no difference(P>0.05). TGAb was lower (P=0.005) when compare T2DM with normal thyroid function group with control group. FT4, TSH, TGAb and TPOAb were all different in T2DM with SCH from T2DM with normal thyroid function(P≤0.001). When we compare the positive rate of TGAb and TPOAb, we found that it was higher in T2DM with SCH than T2DM with normal thyroid function and control group.
3. Comparation of serum lipid
(1) TC, TG, HDL-C, LDL-C and ApoB were different among groups by one-way ANOVA(all P<0.01), and ApoA, Lp(a), GLU and UA had no difference(P>0.05). TC was lower in hyperthyroid group than control group while higher in hypothyroid and subclinical hypothyroid group. TG was lower in hyperthyroid and subclinical hyperthyroid groups than control group. HDL-C was lower in both hyperthyroid and hypothyroid groups. LDL-C was lower in hyperthyroid groups than control group but higher in hypothyroid and subclinical hypothyroid groups. ApoA, Lp(a) and blood glucose had no difference in groups. ApoB was lower in hyperthyroid group than control group and higher in hypothyroid and subclinical hypothyroid groups. UA was higher in hyperthyroid and subclinical hypothyroid groups. TC, LDL-C and ApoB had significant differences after adjudgement of sex, age and BMI.
(2)Our research indicated that TC was higher in SCH group no matter TSH 4.2-10μIU/ml or>10μIU/ml than control group. TC was also higher in TSH>10μIU/ml subgroup than TSH 4.2-10μIU/ml subgroup. TG had no difference among groups. The rising rate of TC was higher when TSH>10μIU/ml, and when TSH 4.2-10μIU/ml, rising rate of TC was higher than control group, but had no statistic meaning. TG was higher in SCH group than control in the subgroup younger than 20-years old. TC and TG in SCH group in male subgroup were higher than control group, TC's difference remained but TG's vanished in female subgroup. TC was also higher in SCH group in BMI<24 subgroup than control group but not in other BMI subgroup. TG showed no difference in any BMI subgroup.
(3) TC, TG, LDL-C, ApoA, ApoB, Lp(a), glucose and UA were all different in T2DM with SCH to control group or T2DM with normal thyroid function to control group. But such index had no differences in T2DM with SCH and T2DM with normal thyroid function.
4. Results of Pearson correlation and multiplt linear regression analysis
(1) The relationship between thyroid function and lipid in each group was showed below:①hyperthyroid group. LnTSH correlated positively with Lp(a), FT4 correlated negatively with TC, HDL-C, LDL-C and Lp(a), FT3 correlated negatively with TC, HDL-C, LDL-C, ApoB and Lp(a).②hypothyroid group. LnTSH correlated positively with TC, HDL-C and LDL-C, FT4 correlated negatively with HDL-C, FT3 had no correlation with such index,③subclinical hypothyroid group. LnTSH correlated positively with TC and TG, FT3 correlated negatively with TC.④subclinical hyperthyroid group and control group. FT3, FT4 and TSH had no correlation with serum lipid, glucose and UA. Multiple linear regression showed that FT4 was predictive variables for TC, LDL-C and ApoB in hyperthyroid group, LnTSH was predictive variable for TC and HDL-C while FT3 was predictive variable for TG in hypothyroid group. LnTSH was predictive variable for TC in subclinical hyperthyroid group.
(2)see(1).
(3) FT3, FT4 and LnTSH had no correlation with TC, TG, HDL-C, LDL-C, ApoA, ApoB, Lp(a) and UA. They had no correlation even after adjudgement of age, sex and BMI. Segregant analysis showed that thyroid function had no correlation with serum lipid and glucose in T2DM with SCH group. LnTSH correlated positively with HDL-C and UA in T2DM with normal thyroid function. Multiple linear regression analysis showed that LnTSH、FT3、FT4 couldn't be predictive variables for serum lipid in T2DM with SCH group and T2DM with normal thyroid function group.
Conclusion:1. TC, TG, HDL-C, LDL-C and ApoB were lower in hyperthyroid group than control group, and TG was lower in subclinical hyperthyroid group than control group. TC, LDL-C, ApoB were higher and HDL-C was lower in hypothyroid group than control group, while TC, LDL-C, ApoB and UA were higher in SCH group than control. ApoA, Lp(a) and glucose had no difference among groups. TC, LDL-C and ApoB were different after adjudgement of age, sex and BMI.
2. Our research indicated that TC was higher in SCH group than control group no matter TSH 4.2-10μIU/ml or>10μIU/ml. TG had no difference among three groups. The rising rate of TC was higher when TSH>10μIU/ml, and when TSH 4.2-10μIU/ml, the rising rate of TC was higher than control group, but had no statistic meaning.
3. TG was higher in SCH group than control group in the subgroup with ages younger than 20y. TC and TG in SCH group in male subgroup were higher than control group, TC were also higher in female subgroup but TG had no difference in SCH group. TC was also higher in SCH group in BMI<24kg/m2 subgroup than control group but not in other BMI subgroup.
4. TC, TG, LDL-C, ApoA, ApoB, Lp(a), glucose and UA were all different in T2DM with SCH to control group or T2DM with normal thyroid function to control group. But such index had no differences in T2DM with SCH and T2DM with normal thyroid function.
5. Correlation and regression analysis indicated that TC, LDL-C and ApoB correlated closely with thyroid function, especially TSH. But in patients with type 2 diabetes, the correlation became not so evident.
目的：1、研究不同甲状腺功能状态下血脂谱、血糖、尿酸的状况,并分析FT3、FT4、TSH等与血脂、血糖、尿酸的相关性。2、分析亚临床甲减患者TSH与血脂间的相关性。3、研究2型糖尿病患者中甲功正常者和合并亚临床甲减者甲状腺功能与血脂间的相关性。
资料与方法：
1、研究对象：(1)收集2007年12月至2009年6月在山东省立医院内分泌科门诊及病房就诊的患者439名,分为甲亢组、亚临床甲亢组、甲减组、亚临床甲减组。并收集同期在我科门诊或病房检查甲状腺功能正常者79例作为对照组。以上入组者均排除肝病、肾病、恶性肿瘤、糖尿病等引起继发性血脂异常的疾病,均为非吸烟者或既往有吸烟史但已戒烟6个月以上,且近3个月内未服用过影响血脂和甲功的药物。(2)将上述患者中的亚临床甲减组与对照组共198例对TSH分层后进行进一步分析。(3)收集2007年12月至2009年6月在我科病房住院治疗的无甲状腺疾病史的2型糖尿病患者102名,检测其甲状腺功能,并按其甲状腺功能分为糖尿病合并亚临床甲减组和糖尿病甲功正常组,并以同期在我科门诊或病房检查甲状腺功能正常且无糖尿病者79例作为对照组。
2、检测指标：患者正常饮食情况下,于夜间12时后禁食,次晨空腹抽取静脉血5m1分装入2个试管,即刻分离血清。一份用于检测甲状腺功能,包括TSH、FT3、FT4、TGAb和TPOAb。另一份检测血清TC、TG、HDL-C、LDL-C、ApoA、ApoB、Lp(a)、血糖、尿酸等指标。
3、统计学方法：因TSH不服从正态分布,故对其进行对数转换后进行分析。各组数值型变量用X±S表示,组间血脂谱、血糖、尿酸比较应用单因素方差分析,两两比较采用q检验。采用Pearson相关及多元回归分析FT3、FT4、TSH等与血脂各指标、血糖、尿酸之间的相关性。上述统计分析均采用SPSS17.0软件包,以P<0.05为差异有统计学意义。
结果：
1、一般资料比较
(1)甲亢组256例(女167例),年龄39.85±12.42岁,BMI 21.71±2.96 kg/m2,亚临床甲亢组12例(女8例),年龄27.33±3.79岁,BMI 22.45±1.40 kg/m2,甲减组52例(女35例),年龄49.45±15.57岁,BMI 25.55±1.99 kg/m2,亚临床甲减组119例(女72例),年龄50.10±11.40岁,BMI 24.44±3.22kg/m2,对照组79例(女50例),年龄41.39±21.07岁,BMI 22.24±4.41kg/m2。各组间性别分布无明显差异,但甲减组和亚临床甲减组较对照组年龄大(P<0.005),而甲亢组和亚临床甲亢组与对照组无明显差异,各组BMI差异亦有显著性,甲减组、亚临床甲减组明显高于甲亢组和对照组(P<0.05)。(2)亚临床甲减组和对照组一般资料比较同(1)。(3)糖尿病亚临床甲减组患者12例(女9例),年龄45.67±16.07岁,BMI 27.24±4.24 kg/m2,糖尿病甲功正常组患者90例(女42例),年龄55.40±13.30岁,BMI 25.73±4.38 kg/m2。对照组资料同前。三组间性别无明显差异,糖尿病甲功正常组年龄较对照组年龄大(P<0.001),糖尿病甲功正常组和糖尿病亚临床甲减组BMI均高于对照组(P<0.05)。
2、甲状腺功能比较
(1)各组间FT3、FT4、TSH、TGAb和TPOAb均有显著差异(P均<0.002)。两两比较发现,甲亢组FT3、FT4明显高于亚临床甲亢组、甲减组、亚临床甲减组和对照组(P均<0.005),甲减组、亚临床甲减组TSH明显高于甲亢组、亚临床甲亢组和正常对照组(P均<0.005),甲亢组TGAb明显低于甲减组(P=0.017),但略高于对照组(P=0.049),甲减组TGAb明显高于亚临床甲减组和对照组(P=0.014、0.001),甲亢组、亚临床甲亢组、甲减组、亚临床甲减组TPOAb均明显高于对照组(P均<0.002)。(2)亚临床甲减组仅TSH和TPOAb明显高于对照组(P均<0.005),余指标与对照组无明显差别。(3)糖尿病并亚临床甲减组和糖尿病甲功正常组及对照组相比,TSH、TGA、TPOAb均有明显差异。两两比较发现,糖尿病亚临床甲减组与对照组相比,TSH、TGAb和TPOAb均有显著升高(P<0.002),而FT3、FT4无明显差异(P>0.05)；糖尿病甲功正常组与对照组比较,除TGAb低于对照组(P=0.005)外,FT4、TSH、TPOAb差异均不明显(P>0.05)；糖尿病亚临床甲减组与糖尿病甲功正常组比较,除FT3无差异外,余指标均有明显差异(P≤0.001)。
3、各组血脂比较
(1)单因素方差分析显示,TC、TG、HDL-C、LDL-C、ApoB在各组之间有显著性差异(P均<0.01),ApoA、Lp(a)、GLU、UA各组间无显著性差异(P>0.05)。两两比较显示,甲亢组TC明显低于对照组(P<0.001),而甲减组和亚临床甲减组则明显高于对照组(P<0.001,0.003)；甲亢组和亚临床甲亢组TG均明显低于对照组(P均<0.001)；HDL-C在甲亢组和甲减组均低于对照组(P=0.001,0.017);甲亢组LDL-C明显低于对照组(P=0.009),而甲减组和亚临床甲减组均明显高于对照组(P均<0.001);ApoA、Lp(a)和血糖在各组无明显差别；ApoB在甲亢组低于对照组(P<0.001),而甲减和亚临床甲减组高于对照组(P<0.001,0.008);UA在甲亢组和亚临床甲减组均高于对照组(P=0.004,0.031)。经年龄、性别和BMI校正后,TC、LDL-C、ApoB仍有显著性差异。
(2)将TSH分层后进行分析发现,在4.2-1OμIU/ml和>10μIU/ml组,TC均明显高于对照组(P分别为0.012和<0.001),而TG在三组间无明显差异。分层分析同时显示,TSH>10μIU/ml组,TC升高率也明显高于对照组(P<0.001),而TSH在4.2-10μIU/ml组TC升高率与对照组相比有升高趋势,但无统计学差异。对年龄进行分层后发现,仅在年龄<20岁组中,TG在亚临床甲减组明显高于对照组(P=0.014),而在其他年龄组中,TC和TG在亚临床甲减组较对照组有升高趋势,但无统计学意义。而在40-60岁年龄组,TG在对照组较亚临床甲减组略高,亦无统计学差异；分性别进行分析显示,亚临床甲减组男性的TC和TG均明显高于对照组(P<0.01),而在女性,亚临床甲减组的TC明显高于对照组(P=0.02),TG两组无明显差异；对BMI进行分层后的分析显示,仅在BMI<24kg/m2亚组中,亚临床甲减组的TC明显高于对照组(P=0.021),其他各亚组中亚临床甲减组的TC较对照组均有升高趋势,但无统计学差异。TG在各亚组中两组比较均无统计学差异。
(3)三组比较,除HDL-C外,其他指标均有显著差异。两两比较发现,无论是糖尿病亚临床甲减组与对照组比较,还是糖尿病甲功正常组与对照组比较,TC、TG、LDL-C、ApoA、ApoB、Lp(a)、GLU、UA均有显著差异(P均<0.001)；而糖尿病亚临床甲减组与糖尿病甲功正常组比较,各项指标均无明显差异。
4、各组Pearson相关和多元线性回归分析结果
(1)经年龄、性别和BMI校正后,各组中血脂与甲功的关系如下所示：甲亢组：LnTSH与Lp(a)显著正相关,FT4与TC、HDL-C、LDL-C和Lp(a)显著负相关,FT3与TC、HDL-C、LDL-C、ApoB、Lp(a)显著负相关；甲减组：LnTSH与TC、HDL-C、LDL-C显著正相关,FT4与HDL-C显著负相关,FT3与上述指标无明显相关；亚临床甲减组：LnTSH与TC显著正相关,FT3与TC显著负相关；在正常甲功组和亚临床甲亢组,FT3、FT4、TSH与血脂、血糖、尿酸均无明显相关性。多元线性回归分析显示,甲亢组FT4可作为TC、HDL-C、LDL-C的预测变量,亚临床甲亢组因例数较少,未做分析；甲减组LnTSH可作为TC、HDL-C的预测变量,FT3可作为TG的预测变量,亚临床甲减组LnTSH可作为TC的预测变量,FT3、FT4均不能作为血脂的预测变量。(2)分析结果见(1)。
(3)FT3、FT4、LnTSH与TC、TG、HDL-C、LDL-C、ApoA、ApoB、Lp(a)、UA等均无显著相关。经年龄、性别和BMI校正后,FT3、FT4、LnTSH与血脂、尿酸仍无相关性。如分组来看,则在糖尿病亚临床甲减组,甲功与血脂、血糖均无相关性,而糖尿病甲功正常组,LnTSH与HDL-C和UA呈显著正相关(P=0.029和0.028)。多元线性回归分析显示,在糖尿病亚临床甲减组和糖尿病甲功正常组LnTSH、FT3、FT4均不能作为血脂各成分的预测变量。
结论：1、甲亢组T、TG、HDL-C、LDL-C、ApoB均明显低于对照组,亚临床甲亢组仅TG低于对照组,甲减组TC、LDL-C、ApoB均高于对照组,HDL-C低于对照组,而亚临床甲减组TC、LDL-C、ApoB、UA高于对照组,ApoA、Lp(a)和血糖在各组无明显差别。经年龄、性别和BMI校正后,TC、LDL-C、ApoB仍有显著性差异。
2、对亚临床甲减组的分析显示,在TSH4.2-10μIU/ml和>10μIU/ml组,TC均明显高于对照组,而TG在三组之间无显著差异。TSH>10μIU/ml组的TC升高率也明显高于对照组,而TSH在4.2-10μIU/ml组TC升高率与对照组相比有升高趋势,但无统计学差异。
3、在年龄<20岁组中,TG在亚临床甲减组明显高于对照组,而在其他年龄组中,TC和TG在亚临床甲减组较对照组有升高趋势,但无统计学意义；亚临床甲减组男性的TC和TG均明显高于对照组,而在女性,亚临床甲减组的TC明显高于对照组,TG两组无明显差异；在BMI<24kg/m2亚组中,亚临床甲减组的TC明显高于对照组,其他各亚组中亚临床甲减组的TC较对照组均有升高趋势,但无统计学差异。TG在各亚组中两组比较均无统计学差异。
4、无论是糖尿病亚临床甲减组与对照组比较,还是糖尿病甲功正常组与对照组比较,除HDL-C外的血脂谱、GLU、UA均有显著差异；而糖尿病亚临床甲减组与糖尿病甲功正常组比较,各项指标均无明显差异。
5、相关及回归分析显示,甲功与血脂中的TC、LDL-C和ApoB密切相关,尤其是TSH与血脂关系更为密切。但在合并糖尿病的患者中FT3、FT4和TSH与血脂的相关性均不明显。
Thyroid hormone (TH) is one of the most important hormone in human body because it influences metabolism of carbohydrate, protein and lipids. And the relation between TH and lipid metabolism was research focus during recent years. TH may has impact on lipid from many aspects including synthesis, mobilization and catabolism, etc, and the regulation mechanism is very complex. Hypothyroidism is an important reason for dyslipidemia clinically. High cholesterol is the most common phenomenon, and triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and lipoprotein(a) will change accordingly. Relation between subclinical hypothyroid and dyslipidemia also leads to attention recently. Some research indicated that serum lipid would change to the direction which more likely to cause atherosclerosis. People may pay more attention to the relation of subclinical hypothyroidism and cardiovascular disease for the reason of high prevanlecce of these two diseases. At the same time, prevalence of type 2 diabetes mellitus become higher and higher, and dyslipidemia is very common among these patients, so the relation between thyroid function and serum lipid in type 2 diabetes also becomes a new problem. And there's still no big sample and systematic clinical research about those questions in our country.
Objective:1. To study changes of serum lipid, glucose and uric acid under different thyroid function, and analyse correlation among FT3、FT4、TSH and serum lipid, glucose and uric acid.2. To study correlation between TSH and lipid in subclinical hypothyroid group.3. To explore relationship of thyroid function and serum lipid in type 2 diabetes mellitus with subclinical hypothyroidism and with normal thyroid function.
Material and methods:
1. Subjects:(1) This cross-sectional study includes 439 subjects whose thyroid function tests revealed abnormal results who were out-patients and in-patients at endocrinology department in Shandong Provincial Hospital, and were devided into four groups including hyperthyroid group, subclinical hyperthyroid group, hypothyroid group and subclinical hypothyroid group by their thyroid function status. And we also collected 79 cases with normal thyroid function as control group. Those with liver function abnormality, abnormal renal function, malignant tumor, diabetes mellitus and diseases which may cause dyslipidemia were exclude. They didn't smoke or prohibit smoking for at least 6 months and they didn't use any drugs which may affect serum lipid and thyroid function for the recent 3 months. (2) We analyzed 198 subjects in subclinical group and control group after TSH graded. (3) 102 diabetic subjects without thyroid disease history were collected who were in-patients at endocrinology department in Shandong Provincial Hospital, and were divided into two groups by thyoid function which were diabetes with subclinical hypothyroid and diabetes with normal thyroid function, and we also collected 79 cases with normal thyroid function as control group.
2. Detected index:Fasting venous blood samples were obtained under normal dietary, and the samples were divided into 2 tubes, and seperated serum immediately. One for detection of thyroid function, including TSH、FT3、FT4、TGAb和TPOAb, and another for TC、TG、HDL-C、LDL-C、ApoA、ApoB、Lp(a)、glucose and uric acid.
3. Statistical analysis:TSH was log transferred for the reason that it didn't obey normal distribution at first. Numeric data were expressed as X±S, one-way ANOVA test was used for comparison means among groups. And post-hoc analysis (LSD method) was used for comparison between each group. Pearson correlation, partial correlation and multiple linear regression analyses were used to determine the correlation between the levels of serum thyroid hormone, serum lipid, glucose and uric acid. SPSS-PC 17.0 (Statistical package for the social sciences, SPSS Inc., Chicago, IL, USA) for MS Windows was used for statistical analyses. P values<0.05 were considered statistically significant.
Results:
1. Comparation of general data (1) 256 cases in hyperthyroid group (167 female),39.85±12.42y old, BMI 21.71±2.96 kg/m2.12 cases in subclinical hyperthyroid group (8 female), 27.33±3.79y old, BMI 22.45±1.40 kg/m2,52 cases in hypothyroid group (35 female), 49.45±15.57y old, BMI 25.55±1.99 kg/m2,119 cases in subclinical hypothyroid group (72 female),50.10±11.40y old, BMI 24.44±3.22kg/m2,79 cases in control group (50 female),41.39±21.07y old, BMI 22.24±4.41 kg/m2. There was no difference in sex distribution, but age in hypothyroid and subclinical hypothyroid group were older than others(P<0.005), and which in hyperthyroid and subclinical hyperthyroid group were same as control group. BMI had difference between groups, which in hypothyroid and subclinical hypothyroid group were higher than control group (P<0.05). (2) Comparation of general data between subclinical hypothyroid and control group see (1). (3) Type 2 diabetes mellitus with subclinical hypothyroid group 12(female 9),45.67±16.07y old, BMI 27.24±4.24 kg/m2, type 2 diabetes mellitus with normal thyroid function 90(42 female),55.40±13.30y old, BMI 25.73±4.38 kg/m2. Data of control group was same as former. Ages in T2DM with normal thyroid function was older than control group(P<0.001), and BMI in T2DM with SCH and normal thyroid function were higher than control group(P<0.05).
2. Comparation of thyroid function (1) FT3, FT4, TSH, TGAb and TPOAb had significant difference in groups. FT3, FT4 were higher in hyperthyroid group than subclinical hyperthyroid group, hypothyroid group, SCH group and control group(all P<0.005), TSH in hypothyroid group and SCH group were higher than hyperthyroid, subclinical hyperthyroid group and control group(all P<0.005), TGAb was lower in hyperthyroid group than hypothyroid group(P=0.017) but a little higher than control group(P=0.049), TGAb in hypothyroid group was much higher than SCH and control group(P=0.014、0.001), TPOAb in hyperthyroid, subclinical hyperthyroid, hypothyroid and SCH group were all much higher than control group(all P<0.002).(2) TSH and TPOAb in SCH group were higher than control group, and other indexes had no significant difference. (3)TSH, TGAb and TPOAb were significant different when compared T2DM with SCH group with T2DM with normal thyroid function group and control group.(P<0.002), FT3, FT4 had no difference(P>0.05). TGAb was lower (P=0.005) when compare T2DM with normal thyroid function group with control group. FT4, TSH, TGAb and TPOAb were all different in T2DM with SCH from T2DM with normal thyroid function(P≤0.001). When we compare the positive rate of TGAb and TPOAb, we found that it was higher in T2DM with SCH than T2DM with normal thyroid function and control group.
3. Comparation of serum lipid
(1) TC, TG, HDL-C, LDL-C and ApoB were different among groups by one-way ANOVA(all P<0.01), and ApoA, Lp(a), GLU and UA had no difference(P>0.05). TC was lower in hyperthyroid group than control group while higher in hypothyroid and subclinical hypothyroid group. TG was lower in hyperthyroid and subclinical hyperthyroid groups than control group. HDL-C was lower in both hyperthyroid and hypothyroid groups. LDL-C was lower in hyperthyroid groups than control group but higher in hypothyroid and subclinical hypothyroid groups. ApoA, Lp(a) and blood glucose had no difference in groups. ApoB was lower in hyperthyroid group than control group and higher in hypothyroid and subclinical hypothyroid groups. UA was higher in hyperthyroid and subclinical hypothyroid groups. TC, LDL-C and ApoB had significant differences after adjudgement of sex, age and BMI.
(2)Our research indicated that TC was higher in SCH group no matter TSH 4.2-10μIU/ml or>10μIU/ml than control group. TC was also higher in TSH>10μIU/ml subgroup than TSH 4.2-10μIU/ml subgroup. TG had no difference among groups. The rising rate of TC was higher when TSH>10μIU/ml, and when TSH 4.2-10μIU/ml, rising rate of TC was higher than control group, but had no statistic meaning. TG was higher in SCH group than control in the subgroup younger than 20-years old. TC and TG in SCH group in male subgroup were higher than control group, TC's difference remained but TG's vanished in female subgroup. TC was also higher in SCH group in BMI<24 subgroup than control group but not in other BMI subgroup. TG showed no difference in any BMI subgroup.
(3) TC, TG, LDL-C, ApoA, ApoB, Lp(a), glucose and UA were all different in T2DM with SCH to control group or T2DM with normal thyroid function to control group. But such index had no differences in T2DM with SCH and T2DM with normal thyroid function.
4. Results of Pearson correlation and multiplt linear regression analysis
(1) The relationship between thyroid function and lipid in each group was showed below:①hyperthyroid group. LnTSH correlated positively with Lp(a), FT4 correlated negatively with TC, HDL-C, LDL-C and Lp(a), FT3 correlated negatively with TC, HDL-C, LDL-C, ApoB and Lp(a).②hypothyroid group. LnTSH correlated positively with TC, HDL-C and LDL-C, FT4 correlated negatively with HDL-C, FT3 had no correlation with such index,③subclinical hypothyroid group. LnTSH correlated positively with TC and TG, FT3 correlated negatively with TC.④subclinical hyperthyroid group and control group. FT3, FT4 and TSH had no correlation with serum lipid, glucose and UA. Multiple linear regression showed that FT4 was predictive variables for TC, LDL-C and ApoB in hyperthyroid group, LnTSH was predictive variable for TC and HDL-C while FT3 was predictive variable for TG in hypothyroid group. LnTSH was predictive variable for TC in subclinical hyperthyroid group.
(2)see(1).
(3) FT3, FT4 and LnTSH had no correlation with TC, TG, HDL-C, LDL-C, ApoA, ApoB, Lp(a) and UA. They had no correlation even after adjudgement of age, sex and BMI. Segregant analysis showed that thyroid function had no correlation with serum lipid and glucose in T2DM with SCH group. LnTSH correlated positively with HDL-C and UA in T2DM with normal thyroid function. Multiple linear regression analysis showed that LnTSH、FT3、FT4 couldn't be predictive variables for serum lipid in T2DM with SCH group and T2DM with normal thyroid function group.
Conclusion:1. TC, TG, HDL-C, LDL-C and ApoB were lower in hyperthyroid group than control group, and TG was lower in subclinical hyperthyroid group than control group. TC, LDL-C, ApoB were higher and HDL-C was lower in hypothyroid group than control group, while TC, LDL-C, ApoB and UA were higher in SCH group than control. ApoA, Lp(a) and glucose had no difference among groups. TC, LDL-C and ApoB were different after adjudgement of age, sex and BMI.
2. Our research indicated that TC was higher in SCH group than control group no matter TSH 4.2-10μIU/ml or>10μIU/ml. TG had no difference among three groups. The rising rate of TC was higher when TSH>10μIU/ml, and when TSH 4.2-10μIU/ml, the rising rate of TC was higher than control group, but had no statistic meaning.
3. TG was higher in SCH group than control group in the subgroup with ages younger than 20y. TC and TG in SCH group in male subgroup were higher than control group, TC were also higher in female subgroup but TG had no difference in SCH group. TC was also higher in SCH group in BMI<24kg/m2 subgroup than control group but not in other BMI subgroup.
4. TC, TG, LDL-C, ApoA, ApoB, Lp(a), glucose and UA were all different in T2DM with SCH to control group or T2DM with normal thyroid function to control group. But such index had no differences in T2DM with SCH and T2DM with normal thyroid function.
5. Correlation and regression analysis indicated that TC, LDL-C and ApoB correlated closely with thyroid function, especially TSH. But in patients with type 2 diabetes, the correlation became not so evident.
引文
1. 白耀,甲状腺病学(基础与临床),科学技术文献出版社,2003年1月,第1版。
2. 叶平,血脂的基础与临床,人民军医出版社,2002年1月,第1版。
3. Evagelos N Liberopoulos, Moses S Elisaf.Dyslipidemia in patients with thyroid disorders. Hormones,2002,1(4):218-223
4. Bandyopadhyay SK, Basu AK, Pal SK, et al. A study on dyslipidaemia in subclinical hypothyroidism. J Indian Med Assoc.2006; 104(11):622-4,626.
5. O'Brien T, Dinneen SF, O'Brien PC, et al. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc.1993; 68(9):860-866.
6. Peters JP, Man EB. The interralations of serum lipids in patients with thyroid disease. J Clin Invest.1943;22(5):715-720.
7. Nikkila EA, Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest.1972;51(8):2103-2114.
8. Tulloch BR, Lewis B, Fraser TR.Triglyceride metabolism in thyroid disease. Lancet.1973,24; 1(7800):391-394.
9. Costantini F, Pierdomenico SD, De Cesare D, et al, Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vase Biol.1998; 18(5):732-737.
10. Lee WY, Suh JY, Rhee EJ, et al. Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lpa levels according to thyroid function status.Arch Med Res.2004; 35(6): 540-545.
11. Canaris GJ, Manowitz NR, Mayor G, Ridgway C, The Colorado thyroid disease prevalence study. Arch Intern Med 2000,160(4):526-534.
12. Liberopoulos E, Miltiadous G, Elisaf M, Impressive lipid changes following hypolipidaemic drug administration can unveil subclinical hyperthyroidism. Diabet Obes Metab,2001,3(2):97-98.
13. Patane S, Marte F. Atrial fibrillation associated with subclinical hyperthyroidism. Int J Cardiol.2009,134 (3):e155-158.
14.刘超,蒋须勤。亚临床甲亢,江苏医药,2000,26(4),294-295.
15. Gull W.W, Transactions of the Clinical Society London,1874,7,180.
16. Bastenie PA, Bonnyns M, Neve P,et al. Clinical and pathological significance of asymptomatic atrophic thyroiditis. A condition of latent hypothyroidism, Lancet, 1967,29;1(7496):915-918.
17. Tsimihodimos V, Bairaktari E, Tzallas C, et al. The incidence of thyroid function abnormalities in patients attending an outpatient lipid clinic. Thyroid 1999,9(4): 365-368.
18. Stone NJ, Secondary causes of hyperlipidemia. Med Clin North Am 1994, 78(1):117-141.
19. Dullaart RPF, Hoogenberg K, Groener JEM, et al, The activity of cholesteryl ester transfer protein is decreased in hypothyroidism:a possible contribution to alterations in high-density lipoproteins. Eur J Clin Invest 1990,20(6):581-587.
20. De Bruin TWA, van Barlingen H, van Linde-Sibenius Trip M, et al, Lipoprotein (a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid and hyperthyroid subjects. J Clin Endocrinol Metab 1993,76(1):121-126.
21. Tzotzas T, Krassas GE, Konstadinidis T, et al, Changes in lipoprotein (a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid 2000,10(9):803-808.
22.冯雨,刘超。甲状腺功能异常对血脂代谢的影响。医学综述。2007,13(16)：1237-1239。
23. Bjorn O Asvold, Lars I Vatten, Tom I L Nilsen et al.The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Euro J of Endocrin,2007,156(2), 181-186.
24. M.Empson, V.Flood, G.Ma, C.J.Eastman et al. Prevalence of thyroid disease in an older Australian population. Intern Medi J,2007,37(4):448-455.
25. Lotz H, Salabe GB, Lipoprotein (a) increase associated with thyroid autoimmunity. Eur J Endocrinol 997,136(1):87-91.
26. Kuzzel WC, Schaffarzick RW, Naugler WE, et al. Some observations on 520 gouty patients. J Chronic Dis,1955;2(6):645-669.
27. Steiger MJ, Watson AR, Morgan AG.Hypothyroidism and renal impairment. J R Soc Med,1991;84(11):688-689.
28. Mclanghlin KJ, Mactier RA, Renal impairment in hypothyroidism. Nephrol Dial Transplant,1994;9(10):1521-1522.
29. Ford HC, Lim WC, Chisnall WN, et al, Renal function and electrolyte levels in hyperthyroidism:urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes. Clin Endocrinol, 1989;30(3):293-301.
30. Raber W, Vukovich T, Vierhapper H. Serum uric acid concentration and thyroid-stimulating-hormone(TSH):results of screening for hyperuricaemia in 2359 consecutive patients with various degrees of thyroid dysfunction. Wien Klin Wochenschr,1999; 111 (8):326-328.
31. Yazar A, Doven O, Atis S, et al. Systolic pulmonary artery pressure and serum uric acid levels in patients with hyperthyroidism.Arch Med Res. 2003;34(1):35-40.
32. Giordano N, Santacroce C, Mattii G, Geraci S,et al. Hyperuricemia and gout in thyroid endocrine disorders.Clin Exp Rheumatol.2001; 19(6):661-665.
33. Akira Sato, Toshihide Shirota, Toshio Shinoda, et al. Hyperuricemia in patients with hyperthyroidism due to Graves' disease. Metabolism,1995,44 (2),207-211
34.乔洁,陈名道。亚临床甲状腺疾病的诊断、治疗及病例分析。中华内分泌代谢杂志,2004,20(2)：2a-1-7.
35. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community:a twenty-year follow-up of the Whickham survey. Clin Endocrinol(Oxf),1995,43(1):55-68.
36. Vanderpump MP, Tunbridge WM, French JM, et al.The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid.1996; 6(3):155-60.
37.李佳,滕卫平,单忠艳等。中国汉族碘适量地区妊娠月份特异性TSH和T4的正常参考范围。中华内分泌代谢杂志。2008,24(6),605-608。
38. Baskin HJ, Cobin RH, Duick DS, et al; American Association of Clinical Endocrinologists-American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract,2002,8(6):457-469.
39. Stathatos N, Watofsky I. Managing subclinical hypothyroidism in women. Women Health Primary Care,2002,5:239-246.
40. Stephen PA. The Endocrine Society:current issues in thyroid disease management. Endocr News,2004,29:23-26.
41. Lee SL. When is the TSH normal? New criteria for diagnosis and management. 12th Annual Meeting of the American Association of Clinical Endocrinologists. San Diego:CA,2003.(thyoidtoday.com).
42. Haugen BR. When isn't the TSH normal and why? Clinical implications and causes.12th Annual Meeting of the American Association of Clinical Endocrinologists. San Diego:CA,2003.(thyroidtoday.com).
43. Surks MI, Goswami G, Daniels GH. The thyrotropin reference range should remain unchanged. J Clin Endocrinol Metab,2005,90 (9):5489-5496.
44. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994):National Health and Nutrition Examination Survey (NHANES Ⅲ). J Clin Endocrinol Metab.2002; 87(2):489-499.
45. Hamilton TE, Davis S, Onstad L, Kopecky KJ. Thyrotropin levels in a population with no clinical, autoantibody, or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism. J Clin Endocrinol Metab.2008,93(4):1224-1230. Epub 2008 Jan 29.
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2. 叶平,血脂的基础与临床,人民军医出版社,2002年1月,第1版。
3. Evagelos N Liberopoulos, Moses S Elisaf.Dyslipidemia in patients with thyroid disorders. Hormones,2002,1(4):218-223
4. Bandyopadhyay SK, Basu AK, Pal SK, et al. A study on dyslipidaemia in subclinical hypothyroidism. J Indian Med Assoc.2006; 104(11):622-4,626.
5. O'Brien T, Dinneen SF, O'Brien PC, et al. Hyperlipidemia in patients with primary and secondary hypothyroidism. Mayo Clin Proc.1993; 68(9):860-866.
6. Peters JP, Man EB. The interralations of serum lipids in patients with thyroid disease. J Clin Invest.1943;22(5):715-720.
7. Nikkila EA, Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest.1972;51(8):2103-2114.
8. Tulloch BR, Lewis B, Fraser TR.Triglyceride metabolism in thyroid disease. Lancet.1973,24; 1(7800):391-394.
9. Costantini F, Pierdomenico SD, De Cesare D, et al, Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vase Biol.1998; 18(5):732-737.
10. Lee WY, Suh JY, Rhee EJ, et al. Plasma CRP, apolipoprotein A-1, apolipoprotein B and Lpa levels according to thyroid function status.Arch Med Res.2004; 35(6): 540-545.
11. Canaris GJ, Manowitz NR, Mayor G, Ridgway C, The Colorado thyroid disease prevalence study. Arch Intern Med 2000,160(4):526-534.
12. Liberopoulos E, Miltiadous G, Elisaf M, Impressive lipid changes following hypolipidaemic drug administration can unveil subclinical hyperthyroidism. Diabet Obes Metab,2001,3(2):97-98.
13. Patane S, Marte F. Atrial fibrillation associated with subclinical hyperthyroidism. Int J Cardiol.2009,134 (3):e155-158.
14.刘超,蒋须勤。亚临床甲亢,江苏医药,2000,26(4),294-295.
15. Gull W.W, Transactions of the Clinical Society London,1874,7,180.
16. Bastenie PA, Bonnyns M, Neve P,et al. Clinical and pathological significance of asymptomatic atrophic thyroiditis. A condition of latent hypothyroidism, Lancet, 1967,29;1(7496):915-918.
17. Tsimihodimos V, Bairaktari E, Tzallas C, et al. The incidence of thyroid function abnormalities in patients attending an outpatient lipid clinic. Thyroid 1999,9(4): 365-368.
18. Stone NJ, Secondary causes of hyperlipidemia. Med Clin North Am 1994, 78(1):117-141.
19. Dullaart RPF, Hoogenberg K, Groener JEM, et al, The activity of cholesteryl ester transfer protein is decreased in hypothyroidism:a possible contribution to alterations in high-density lipoproteins. Eur J Clin Invest 1990,20(6):581-587.
20. De Bruin TWA, van Barlingen H, van Linde-Sibenius Trip M, et al, Lipoprotein (a) and apolipoprotein B plasma concentrations in hypothyroid, euthyroid and hyperthyroid subjects. J Clin Endocrinol Metab 1993,76(1):121-126.
21. Tzotzas T, Krassas GE, Konstadinidis T, et al, Changes in lipoprotein (a) levels in overt and subclinical hypothyroidism before and during treatment. Thyroid 2000,10(9):803-808.
22.冯雨,刘超。甲状腺功能异常对血脂代谢的影响。医学综述。2007,13(16)：1237-1239。
23. Bjorn O Asvold, Lars I Vatten, Tom I L Nilsen et al.The association between TSH within the reference range and serum lipid concentrations in a population-based study. The HUNT Study. Euro J of Endocrin,2007,156(2), 181-186.
24. M.Empson, V.Flood, G.Ma, C.J.Eastman et al. Prevalence of thyroid disease in an older Australian population. Intern Medi J,2007,37(4):448-455.
25. Lotz H, Salabe GB, Lipoprotein (a) increase associated with thyroid autoimmunity. Eur J Endocrinol 997,136(1):87-91.
26. Kuzzel WC, Schaffarzick RW, Naugler WE, et al. Some observations on 520 gouty patients. J Chronic Dis,1955;2(6):645-669.
27. Steiger MJ, Watson AR, Morgan AG.Hypothyroidism and renal impairment. J R Soc Med,1991;84(11):688-689.
28. Mclanghlin KJ, Mactier RA, Renal impairment in hypothyroidism. Nephrol Dial Transplant,1994;9(10):1521-1522.
29. Ford HC, Lim WC, Chisnall WN, et al, Renal function and electrolyte levels in hyperthyroidism:urinary protein excretion and the plasma concentrations of urea, creatinine, uric acid, hydrogen ion and electrolytes. Clin Endocrinol, 1989;30(3):293-301.
30. Raber W, Vukovich T, Vierhapper H. Serum uric acid concentration and thyroid-stimulating-hormone(TSH):results of screening for hyperuricaemia in 2359 consecutive patients with various degrees of thyroid dysfunction. Wien Klin Wochenschr,1999; 111 (8):326-328.
31. Yazar A, Doven O, Atis S, et al. Systolic pulmonary artery pressure and serum uric acid levels in patients with hyperthyroidism.Arch Med Res. 2003;34(1):35-40.
32. Giordano N, Santacroce C, Mattii G, Geraci S,et al. Hyperuricemia and gout in thyroid endocrine disorders.Clin Exp Rheumatol.2001; 19(6):661-665.
33. Akira Sato, Toshihide Shirota, Toshio Shinoda, et al. Hyperuricemia in patients with hyperthyroidism due to Graves' disease. Metabolism,1995,44 (2),207-211
34.乔洁,陈名道。亚临床甲状腺疾病的诊断、治疗及病例分析。中华内分泌代谢杂志,2004,20(2)：2a-1-7.
35. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of thyroid disorders in the community:a twenty-year follow-up of the Whickham survey. Clin Endocrinol(Oxf),1995,43(1):55-68.
36. Vanderpump MP, Tunbridge WM, French JM, et al.The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community. Thyroid.1996; 6(3):155-60.
37.李佳,滕卫平,单忠艳等。中国汉族碘适量地区妊娠月份特异性TSH和T4的正常参考范围。中华内分泌代谢杂志。2008,24(6),605-608。
38. Baskin HJ, Cobin RH, Duick DS, et al; American Association of Clinical Endocrinologists-American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract,2002,8(6):457-469.
39. Stathatos N, Watofsky I. Managing subclinical hypothyroidism in women. Women Health Primary Care,2002,5:239-246.
40. Stephen PA. The Endocrine Society:current issues in thyroid disease management. Endocr News,2004,29:23-26.
41. Lee SL. When is the TSH normal? New criteria for diagnosis and management. 12th Annual Meeting of the American Association of Clinical Endocrinologists. San Diego:CA,2003.(thyoidtoday.com).
42. Haugen BR. When isn't the TSH normal and why? Clinical implications and causes.12th Annual Meeting of the American Association of Clinical Endocrinologists. San Diego:CA,2003.(thyroidtoday.com).
43. Surks MI, Goswami G, Daniels GH. The thyrotropin reference range should remain unchanged. J Clin Endocrinol Metab,2005,90 (9):5489-5496.
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