雌、雄激素和维生素D及其受体在甲状腺结节患者血清及甲状腺组织中的水平

发布时间：2018-05-14 15:17

本文选题：甲状腺结节 + 雌激素　；参考：《河北医科大学》2015年硕士论文

【摘要】：目的:甲状腺结节是临床中最常见的一种甲状腺良性病变。其病因目前仍不明了,很可能由多种因素所致,如遗传、雌激素等。根据流行病学结果显示,结节性甲状腺肿患者多为女性,但绝经后的女性与相同年龄阶段的男性甲状腺结节的发病率是类似的,并且随着年龄的增加而增加。另外,研究已初步确定,雌激素对甲状腺癌细胞有促增殖的作用。据此推断,结节性甲状腺肿的发病可能与雌激素水平有关。然而,男性和绝经后的女性,他们的结节形成与雌激素水平有关吗?雄激素是性激素中的另一种甾体激素,也通过其专一的受体介导发挥多种生物学效应,也是雌激素合成的前体。研究表明,雄激素受体在甲状腺癌组织中的阳性率为42.5%,提示雄激素可能在甲状腺结节的发生中起一定作用。这与甲状腺结节的生成有关吗?维生素D是脂溶性维生素,为开环甾体激素。研究证实,维生素D有促甲状腺细胞凋亡的作用,自身免疫性甲状腺疾病与维生素D缺乏有关。维生素D缺乏与甲状腺结节的发生有关吗?为确定上述因素与甲状腺结节的生成是否有关,本实验以男性、绝经前和绝经后女性甲状腺结节患者作为研究对象,测定其外周血以及结节组织与结节旁正常组织中的雌二醇(E2),雌激素受体(ERα,ERβ)、雄激素受体(AR),维生素D受体(VDR)的水平,血清中甲状腺功能指标、雌二醇(E2)、雄激素睾酮(T)及25-羟基维生素D的水平(代表维生素D的水平),探讨这些因素与甲状腺结节形成的关系,为预防和治疗该种疾病提供实验的依据。方法:1取材和分组本实验所用标本取自河北医科大学第二医院腺体外科2014年5月至8月手术切除的甲状腺肿物的组织。将经病理诊断为甲状腺结节的标本,分为结节和结节旁正常组织,分别置于冻存管中,冻于-80℃冰箱中,用于E2、ERα,ERβ,AR、和VDR的测定。同时采集甲状腺肿物患者术前的空腹血清,用于甲状腺功能、睾酮、雌二醇、25-羟基维生素D的测定。实验组、对照组、血清三者均取自同一名患者的标本。2血清中甲状腺功能的测定采用直接化学发光法测定血清中FT3、FT4、TSH浓度。3血清中睾酮及雌二醇的测定采用化学发光法,用美国贝克曼库尔Unicel Dxi 800 Access免疫分析系统仪器测定血清睾酮(T)及雌二醇(E2)含量。4血清中25羟基维生素D的测定采用酶联免疫吸附试验法(ELISA),用Immunodiagnosticsytems生产的25-羟基维生素D测定试剂盒,在美国BIO-TEK ELx800酶标仪上,测定血清中25-羟基维生素D的含量。5甲状腺组织中E2、AR、VDR、ERα、ERβ的测定采用酶联免疫吸附试验法(ELISA),用武汉优尔生生物工程有限公司生产的雌二醇(E2)检测试剂盒、雄激素受体(AR)检测试剂盒、维生素D受体(VDR)检测试剂盒,雌激素受体(ERα、ERβ)检测试剂盒,在美国BIO-TEK的ELx800酶标仪上,测定结节组织及结节旁正常组织中的E2、AR、VDR、ERα、ERβ的含量。6数据分析实验数据采用SPSS 21.0软件进行统计学分析。数据经检验,均不符合正态分布,因此计量资料采用中位数(最小值,最大值)表示,组间差异采用秩和检验分析,P0.05为差异有统计学意义。相关性使用Spearman秩相关分析,P0.05为差异有统计学意义。结果:1一般资料42例甲状腺组织结节标本及结节旁正常组织标本,均为成对标本。女性33例,年龄16—71岁,分为绝经前女性组(14例)和绝经后女性组(19例);男性9例,年龄18—83岁,为男性组。2血清中甲状腺功能因患者血清FT3、FT4、TSH浓度均在正常范围,所有患者甲状腺功能正常。3甲状腺结节患者的血清中睾酮、雌二醇以及25-羟基维生素D水平3.1血清中睾酮(T)水平患者血清睾酮水平均在其正常值范围。男性为[2.88(0.04 7.03)ng/ml],绝经前女性睾酮水平[0.31(0.13 0.77)ng/ml]和绝经后女性睾酮水平[0.23(0.04 2.77)ng/ml]。经单样本秩和检验,男性较女性高(Z=-3.051,P=0.002),绝经前较绝经后的高(Z=-2.023,P=0.043)。3.2血清中雌二醇(E2)水平经单样本秩和检验,患者血清雌二醇水平:男性为[25(16 78)pg/ml]在其正常范围(7.63-42.6)pg/ml,低于绝经前女性雌二醇水平[39(20 253)pg/ml,P0.05],但与绝经后女性雌二醇水平[23(11 37)pg/ml]无统计学差异;绝经前和绝经后水平均在其正常值范围内。3.3血清中25-羟基维生素D(25-OH-Vit D)水平经单样本秩和检验,患者血清25-羟基维生素D水平:男性为[49.01(26.41 81.71)nmol/L],绝经前女性25羟基维生素D含量为[40.88(19.23 77.96)nmol/L];绝经后女性25羟基维生素D水平为[23(19.30 122.51)nmol/L]。三者之间无统计学差异。三组甲状腺结节患者均为维生素D缺乏状态。4甲状腺结节患者甲状腺组织中雌二醇(E2)雌激素受体(ERα,ERβ)水平4.1甲状腺组织中雌二醇(E2)水平男性结节组E2水平[11.17(9.84 15.03)pg/ml]高于结节旁正常组织中E2水平[4.16(3.00 6.02)pg/ml],两者差异有统计学意义(Z=-3.58,P0.01)。绝经前女性结节组E2水平[12.05(8.98 21.67)pg/ml]高于结节旁正常组织中E2水平[3.96(2.64 5.61)pg/ml],两者差异有统计学意义(Z=-4.5,P0.001)。绝经后女性结节组E2水平[11.38(5.17 15.75)pg/ml]高于结节旁正常组织中E2水平[4.18(2.62 6.98)pg/ml],两者差异有统计学意义(Z=-5.153,P0.001)。4.2甲状腺组织中雌激素受体α(ERα)水平男性结节组ERα水平[23.41(20.94 31.23)ng/ml]高于结节旁正常组织中ERα水平[18.51(14.68 20.76)ng/ml],两者差异有统计学意义((Z=3.576,P0.001)。绝经前女性结节组ERα水平[24.28(18.09 30.51)ng/ml]高于结节旁正常组织中ERα水平[3.96(2.64 5.61)ng/ml],两者差异有统计学意义(Z=-4.044,P0.001)。绝经后女性结节组ERα水平[24.73(17.48 51.48)ng/ml]高于结节旁正常组织中ERα水平[17.34(12.05 23.32)ng/ml],两者差异有统计学意义(Z=-4.511,P0.001)。4.3甲状腺组织中雌激素受体β(ERβ)水平男性结节组ERβ水平[13.85(11.61 23.85)ng/ml]高于结节旁正常组织中ERβ水平[9.62(6.94 11.44)ng/ml],两者差异有统计学意义(Z=-3.58,P0.001)。绝经前女性结节组ERβ水平[13.72(9.31 22.62)pg/ml]高于结节旁正常组织中ERβ水平[9.11(7.20 12.83)ng/ml],两者差异有统计学意义(Z=-4.043,P0.001)。绝经后女性结节组ERβ水平[15.25(8.85 47.44)pg/ml]高于结节旁正常组织中ERβ水平[8.75(5.33 13.78)pg/ml],两者差异有统计学意义(Z=-4.54,P0.001)。5甲状腺结节患者甲状腺组织中雄激素受体(AR)水平男性结节组AR水平[4.69(3.07 5.23)ng/ml]高于结节旁正常组织中AR水平[2.71(1.70 3.72)ng/ml],两者差异有统计学意义(Z=-3.046,P=0.002)。绝经前女性结节组AR水平[4.53(3.49 5.25)ng/ml]高于结节旁正常组织中AR水平[2.95(2.28 3.66)ng/ml],两者差异有统计学意义(Z=-4.227,P0.001)。绝经后女性结节组AR水平[4.75(3.19 5.69)ng/ml]高于结节旁正常组织中AR水平[2.99(2.07 3.95)ng/ml],两者差异有统计学意义(Z=-4.818,P0.001)。6甲状腺结节患者甲状腺组织中维生素D受体(VDR)水平男性结节组VDR水平[2.58(2.24 3.46)ng/ml]低于结节旁正常组织中VDR水平[4.27(3.64 8.40)ng/ml],两者差异有统计学意义(Z=-3.576,P0.001)。绝经前女性结节组VDR水平[2.66(1.91 3.00)ng/ml]低于于结节旁正常组织中VDR水平[4.30(3.41 10.41)ng/ml],两者差异有统计学意义(Z=-4.503,P0.001)。绝经后女性结节组VDR水平[2.61(2.21 3.83)ng/ml]低于结节旁正常组织中VDR水平[4.44(3.37 12.52)ng/ml],两者差异有统计学意义(Z=-5.153,P0.001)。结论:1甲状腺结节局部的高E2水平以及高ERα和ERβ水平与结节的发生有关。2甲状腺结节局部的高AR水平可能与甲状腺结节的形成有关。3维生素D的缺乏以及甲状腺结节局部的低VDR水平与甲状腺结节的形成有关。
[Abstract]:Objective: thyroid nodule is the most common benign thyroid disease in clinical. Its etiology is still unknown, and it is likely to be caused by a variety of factors, such as heredity, estrogen and so on. According to epidemiological results, most patients with nodular goiter are female, but postmenopausal women and male thyroid nodules at the same age stage. The disease rate is similar and increases with age. In addition, the study has preliminarily identified the effect of estrogen on the proliferation of thyroid cancer cells. Accordingly, it is concluded that the pathogenesis of nodular goiter may be related to the level of estrogen. However, male and postmenopausal women, their nodules are related to estrogen level? Hormone is another steroid hormone in the sex hormone, which is also a precursor of estrogen synthesis through its specific receptor. Studies have shown that the positive rate of androgen receptor in thyroid cancer tissue is 42.5%, suggesting that androgen may play a role in the occurrence of thyroid nodules. This is associated with thyroid nodules. Is it related to the formation of vitamin D, a fat soluble vitamin, as an open steroid hormone. Studies have shown that vitamin D has a role in the apoptosis of thyroid cells. Autoimmune thyroid disease is associated with vitamin D deficiency. Is vitamin D deficiency associated with the occurrence of thyroid nodules? To determine whether the above factors are associated with the formation of thyroid nodules. In this study, the subjects were male, premenopausal and postmenopausal women with thyroid nodules, and the peripheral blood as well as the estradiol (E2), estrogen receptor (ER a, ER beta), androgen receptor (AR), vitamin D receptor (VDR), serum thyroid function, estradiol (E2) and male irritant were measured in peripheral blood and nodular tissue and paracular normal tissue. The level of testosterone (T) and 25- hydroxyvitamin D (representing the level of vitamin D) and the relationship between these factors and the formation of thyroid nodules to provide the basis for the prevention and treatment of this disease. Methods: 1 samples taken and grouped in this experiment were taken from the surgical resection of glandular surgery in the second hospital of Hebei Medical University from May 2014 to August. Specimens of thyroid nodules, divided into nodules and paracular tissues, were divided into nodules and paracular normal tissues. They were placed in cryopreservation tubes and frozen at -80 centigrade refrigerators for the determination of E2, ER alpha, ER beta, AR, and VDR. At the same time, the fasting serum of thyroid tumor patients was collected for thyroid function, testosterone, estradiol, 25- hydroxyl group. Determination of vitamin D, experimental group, control group, three serum samples from the same patient's.2 serum thyroid function determination by direct chemiluminescence determination of serum FT3, FT4, TSH concentration.3 serum testosterone and estradiol determination by chemiluminescence method, the United States Backman Kurt Unicel Dxi 800 Access immunoassay system Determination of serum testosterone (T) and estradiol (E2) content in.4 serum, the determination of 25 hydroxyl vitamin D in serum was determined by enzyme linked immunosorbent assay (ELISA). The determination of 25- hydroxyvitamin D in Immunodiagnosticsytems was used to determine the content of 25- hydroxy vitamin D in the thyroid tissue E2, AR, VDR, ER a, and ER beta were determined by enzyme linked immunosorbent assay (ELISA). The estrogen receptor (E2) detection kit produced by Wuhan yelson Bioengineering Co., Ltd., androgens receptor (AR) detection kit, vitamin D receptor (VDR) detection kit, estrogen receptor (ER alpha, ER beta) detection kit, and the enzyme labeling instrument in the United States were used. To determine the content of E2, AR, VDR, ER a, ER beta in the nodular tissue and the normal tissue of the nodules, the data of.6 data analysis were analyzed by SPSS 21 software. The data were not in accordance with the normal distribution, so the data were represented by the median (minimum, maximum), and the difference between groups was analyzed by the rank sum test, and P0.05 was poor. The correlation was statistically significant. The correlation using Spearman rank correlation analysis, P0.05 was statistically significant. Results 1 general data 42 cases of thyroid nodule specimens and paracular normal tissue specimens were paired specimens. Women 33 cases, age 16 to 71 years, divided into premenopausal women (14 cases) and postmenopausal women group (19 cases); male 9 cases, year. Aged 18 to 83 years old, the serum levels of FT3, FT4, TSH in the serum of male patients with.2 serum were in normal range. The serum testosterone, estradiol, and 25- hydroxyvitamin D level 3.1 in all patients with thyroid function normal.3 thyroid nodules were in the normal range of serum testosterone level in patients with serum testosterone (T) level 3.1. [2.88 (0.04 7.03) ng/ml], premenopausal women's testosterone level [0.31 (0.13 0.77) ng/ml] and postmenopausal women's testosterone level [0.23 (0.04 2.77) ng/ml]. were tested by single sample rank and test, men were higher than women (Z=-3.051, P=0.002), and the level of estradiol (E2) in serum of postmenopausal higher than postmenopausal (Z=-2.023, P=0.043).3.2 serum was tested by single sample rank sum test. Serum estradiol levels: male [25 (1678) pg/ml] in its normal range (7.63-42.6) pg/ml, lower than pre menopausal female estradiol level [39 (20253) pg/ml, P0.05], but no statistical difference with [23 (1137) pg/ml] after menopause female estradiol (1137); both premenopausal and postmenopausal levels in the normal range of.3.3 serum 25- hydroxy vitamin A The level of D (25-OH-Vit D) was tested by the single sample rank sum test, the serum 25- hydroxyl vitamin D level of the patient: the male was [49.01 (26.41 81.71) nmol/L], and the 25 hydroxyvitamin D content of the premenopausal women was [40.88 (19.23 77.96) nmol/L]; the 25 hydroxyvitamin D levels of postmenopausal women were not statistically different between 23 (19.30 122.51) nmol/L]. three. Three a The patients with nodular nodules were both vitamin D deficiency and.4 thyroid nodules. The levels of estrogen receptor (E2), estrogen receptor (ER, ER beta) in thyroid tissue were 4.1. The E2 level [11.17 (9.84 15.03) pg/ml] in the male nodular group of thyroid tissue (9.84 15.03) pg/ml] was higher than the E2 level [4.16 (3 6.02) pg/ml], there was a difference between the two groups. The study significance (Z=-3.58, P0.01). The E2 level [12.05 (8.98 21.67) pg/ml] of the premenopausal female nodule group was higher than the E2 level [3.96 (2.64 5.61) pg/ml] in the paracular normal tissue. The difference was statistically significant (Z=-4.5, P0.001). The E2 level [11.38 (5.17 15.75) in postmenopausal women nodular group was higher than that in the normal tissue adjacent to the nodules (2.62 6.9). 8) pg/ml], the difference was statistically significant (Z=-5.153, P0.001) in.4.2 thyroid tissue, the level of ER alpha in the estrogen receptor alpha (ER alpha) level in the male nodule group [23.41 (20.94 31.23) ng/ml] was higher than the ER alpha [18.51 (14.68 20.76) ng/ml] in the normal tissue adjacent to the nodules. The difference between the two groups was statistically significant (Z=3.576,). The level of [24.28 (18.09 30.51) ng/ml] was higher than that of ER alpha level [3.96 (2.64 5.61) ng/ml] in the normal nodular tissue (Z=-4.044, P0.001). The ER a level [24.73 (17.48 51.48) ng/ml] of the postmenopausal women nodular group was higher than that of ER alpha level [17.34 (12.05 23.32) in the normal tissue adjacent to the nodules (12.05 23.32). =-4.511, P0.001) in.4.3 thyroid tissue, the level of ER beta level [13.85 (11.61 23.85) ng/ml] in the male nodule group was higher than the ER beta level [9.62 (6.94 11.44) ng/ml] in the normal tissue adjacent to the nodules. The difference was statistically significant (Z=-3.58, P0.001). The level of beta level in the premenstrual group was higher than that of the nodules (9.31 22.62). The difference of ER beta level [9.11 (7.20 12.83) ng/ml] in normal tissue was statistically significant (Z=-4.043, P0.001). The ER beta level of [15.25 (8.85 47.44) pg/ml] in postmenopausal women nodular group was higher than that of [8.75 (5.33 13.78) pg/ml] in the normal tissue adjacent to the nodules, and the difference was statistically significant (Z=-4.54 The AR level [4.69 (3.07 5.23) of androgen receptor (AR) level in the male nodular group was higher than that of AR level [2.71 (1.70 3.72) ng/ml] in the normal nodular tissue. The difference was statistically significant (Z=-3.046, P=0.002). AR level was [4.53 (3.49 5.25) in the premenopausal women nodule group (3.49 5.25). (2.28 3.66) (2.28 3.66) ) ng/ml], the differences were statistically significant (Z=-4.227, P0.001). AR level [4.75 (3.19 5.69) ng/ml] in postmenopausal female nodule group was higher than AR level [2.99 (2.07 3.95) ng/ml] in normal nodular tissue. The difference was statistically significant (Z=-4.818, P0.001) in the thyroid tissue of patients with.6 thyroid nodules. Group VDR level [2.58 (2.24 3.46) ng/ml] was lower than that of VDR level [4.27 (3.64 8.40) ng/ml] in normal nodular tissue (Z=-3.576, P0.001). The VDR level [2.66 (1.91 3) ng/ml] in premenopausal women nodule group was lower than that of VDR level (3.41 10.41) in normal tissue (3.41 10.41). 4.503, P0.001). The VDR level [2.61 (2.21 3.83) of the postmenopausal female nodule group was lower than the VDR level [4.44 (3.37 12.52) ng/ml] in the paracular normal tissue. The difference was statistically significant (Z=-5.153, P0.001). Conclusion: the high E2 level of the local thyroid nodules and the high ER alpha and ER beta level are related to the nodules. High AR level may be related to the formation of thyroid nodules,.3 vitamin D deficiency and local low VDR level in thyroid nodules are related to the formation of thyroid nodules.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R581

【参考文献】