發(fā)布時(shí)間：2018-05-14 15:17

  本文選題：甲狀腺結(jié)節(jié) + 雌激素　； 參考：《河北醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:甲狀腺結(jié)節(jié)是臨床中最常見的一種甲狀腺良性病變。其病因目前仍不明了,很可能由多種因素所致,如遺傳、雌激素等。根據(jù)流行病學(xué)結(jié)果顯示,結(jié)節(jié)性甲狀腺腫患者多為女性,但絕經(jīng)后的女性與相同年齡階段的男性甲狀腺結(jié)節(jié)的發(fā)病率是類似的,并且隨著年齡的增加而增加。另外,研究已初步確定,雌激素對(duì)甲狀腺癌細(xì)胞有促增殖的作用。據(jù)此推斷,結(jié)節(jié)性甲狀腺腫的發(fā)病可能與雌激素水平有關(guān)。然而,男性和絕經(jīng)后的女性,他們的結(jié)節(jié)形成與雌激素水平有關(guān)嗎?雄激素是性激素中的另一種甾體激素,也通過其專一的受體介導(dǎo)發(fā)揮多種生物學(xué)效應(yīng),也是雌激素合成的前體。研究表明,雄激素受體在甲狀腺癌組織中的陽(yáng)性率為42.5%,提示雄激素可能在甲狀腺結(jié)節(jié)的發(fā)生中起一定作用。這與甲狀腺結(jié)節(jié)的生成有關(guān)嗎?維生素D是脂溶性維生素,為開環(huán)甾體激素。研究證實(shí),維生素D有促甲狀腺細(xì)胞凋亡的作用,自身免疫性甲狀腺疾病與維生素D缺乏有關(guān)。維生素D缺乏與甲狀腺結(jié)節(jié)的發(fā)生有關(guān)嗎?為確定上述因素與甲狀腺結(jié)節(jié)的生成是否有關(guān),本實(shí)驗(yàn)以男性、絕經(jīng)前和絕經(jīng)后女性甲狀腺結(jié)節(jié)患者作為研究對(duì)象,測(cè)定其外周血以及結(jié)節(jié)組織與結(jié)節(jié)旁正常組織中的雌二醇(E2),雌激素受體(ERα,ERβ)、雄激素受體(AR),維生素D受體(VDR)的水平,血清中甲狀腺功能指標(biāo)、雌二醇(E2)、雄激素睪酮(T)及25-羥基維生素D的水平(代表維生素D的水平),探討這些因素與甲狀腺結(jié)節(jié)形成的關(guān)系,為預(yù)防和治療該種疾病提供實(shí)驗(yàn)的依據(jù)。方法:1取材和分組本實(shí)驗(yàn)所用標(biāo)本取自河北醫(yī)科大學(xué)第二醫(yī)院腺體外科2014年5月至8月手術(shù)切除的甲狀腺腫物的組織。將經(jīng)病理診斷為甲狀腺結(jié)節(jié)的標(biāo)本,分為結(jié)節(jié)和結(jié)節(jié)旁正常組織,分別置于凍存管中,凍于-80℃冰箱中,用于E2、ERα,ERβ,AR、和VDR的測(cè)定。同時(shí)采集甲狀腺腫物患者術(shù)前的空腹血清,用于甲狀腺功能、睪酮、雌二醇、25-羥基維生素D的測(cè)定。實(shí)驗(yàn)組、對(duì)照組、血清三者均取自同一名患者的標(biāo)本。2血清中甲狀腺功能的測(cè)定采用直接化學(xué)發(fā)光法測(cè)定血清中FT3、FT4、TSH濃度。3血清中睪酮及雌二醇的測(cè)定采用化學(xué)發(fā)光法,用美國(guó)貝克曼庫(kù)爾Unicel Dxi 800 Access免疫分析系統(tǒng)儀器測(cè)定血清睪酮(T)及雌二醇(E2)含量。4血清中25羥基維生素D的測(cè)定采用酶聯(lián)免疫吸附試驗(yàn)法(ELISA),用Immunodiagnosticsytems生產(chǎn)的25-羥基維生素D測(cè)定試劑盒,在美國(guó)BIO-TEK ELx800酶標(biāo)儀上,測(cè)定血清中25-羥基維生素D的含量。5甲狀腺組織中E2、AR、VDR、ERα、ERβ的測(cè)定采用酶聯(lián)免疫吸附試驗(yàn)法(ELISA),用武漢優(yōu)爾生生物工程有限公司生產(chǎn)的雌二醇(E2)檢測(cè)試劑盒、雄激素受體(AR)檢測(cè)試劑盒、維生素D受體(VDR)檢測(cè)試劑盒,雌激素受體(ERα、ERβ)檢測(cè)試劑盒,在美國(guó)BIO-TEK的ELx800酶標(biāo)儀上,測(cè)定結(jié)節(jié)組織及結(jié)節(jié)旁正常組織中的E2、AR、VDR、ERα、ERβ的含量。6數(shù)據(jù)分析實(shí)驗(yàn)數(shù)據(jù)采用SPSS 21.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。數(shù)據(jù)經(jīng)檢驗(yàn),均不符合正態(tài)分布,因此計(jì)量資料采用中位數(shù)(最小值,最大值)表示,組間差異采用秩和檢驗(yàn)分析,P0.05為差異有統(tǒng)計(jì)學(xué)意義。相關(guān)性使用Spearman秩相關(guān)分析,P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:1一般資料42例甲狀腺組織結(jié)節(jié)標(biāo)本及結(jié)節(jié)旁正常組織標(biāo)本,均為成對(duì)標(biāo)本。女性33例,年齡16—71歲,分為絕經(jīng)前女性組(14例)和絕經(jīng)后女性組(19例);男性9例,年齡18—83歲,為男性組。2血清中甲狀腺功能因患者血清FT3、FT4、TSH濃度均在正常范圍,所有患者甲狀腺功能正常。3甲狀腺結(jié)節(jié)患者的血清中睪酮、雌二醇以及25-羥基維生素D水平3.1血清中睪酮(T)水平患者血清睪酮水平均在其正常值范圍。男性為[2.88(0.04 7.03)ng/ml],絕經(jīng)前女性睪酮水平[0.31(0.13 0.77)ng/ml]和絕經(jīng)后女性睪酮水平[0.23(0.04 2.77)ng/ml]。經(jīng)單樣本秩和檢驗(yàn),男性較女性高(Z=-3.051,P=0.002),絕經(jīng)前較絕經(jīng)后的高(Z=-2.023,P=0.043)。3.2血清中雌二醇(E2)水平經(jīng)單樣本秩和檢驗(yàn),患者血清雌二醇水平:男性為[25(16 78)pg/ml]在其正常范圍(7.63-42.6)pg/ml,低于絕經(jīng)前女性雌二醇水平[39(20 253)pg/ml,P0.05],但與絕經(jīng)后女性雌二醇水平[23(11 37)pg/ml]無統(tǒng)計(jì)學(xué)差異;絕經(jīng)前和絕經(jīng)后水平均在其正常值范圍內(nèi)。3.3血清中25-羥基維生素D(25-OH-Vit D)水平經(jīng)單樣本秩和檢驗(yàn),患者血清25-羥基維生素D水平:男性為[49.01(26.41 81.71)nmol/L],絕經(jīng)前女性25羥基維生素D含量為[40.88(19.23 77.96)nmol/L];絕經(jīng)后女性25羥基維生素D水平為[23(19.30 122.51)nmol/L]。三者之間無統(tǒng)計(jì)學(xué)差異。三組甲狀腺結(jié)節(jié)患者均為維生素D缺乏狀態(tài)。4甲狀腺結(jié)節(jié)患者甲狀腺組織中雌二醇(E2)雌激素受體(ERα,ERβ)水平4.1甲狀腺組織中雌二醇(E2)水平男性結(jié)節(jié)組E2水平[11.17(9.84 15.03)pg/ml]高于結(jié)節(jié)旁正常組織中E2水平[4.16(3.00 6.02)pg/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-3.58,P0.01)。絕經(jīng)前女性結(jié)節(jié)組E2水平[12.05(8.98 21.67)pg/ml]高于結(jié)節(jié)旁正常組織中E2水平[3.96(2.64 5.61)pg/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.5,P0.001)。絕經(jīng)后女性結(jié)節(jié)組E2水平[11.38(5.17 15.75)pg/ml]高于結(jié)節(jié)旁正常組織中E2水平[4.18(2.62 6.98)pg/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-5.153,P0.001)。4.2甲狀腺組織中雌激素受體α(ERα)水平男性結(jié)節(jié)組ERα水平[23.41(20.94 31.23)ng/ml]高于結(jié)節(jié)旁正常組織中ERα水平[18.51(14.68 20.76)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義((Z=3.576,P0.001)。絕經(jīng)前女性結(jié)節(jié)組ERα水平[24.28(18.09 30.51)ng/ml]高于結(jié)節(jié)旁正常組織中ERα水平[3.96(2.64 5.61)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.044,P0.001)。絕經(jīng)后女性結(jié)節(jié)組ERα水平[24.73(17.48 51.48)ng/ml]高于結(jié)節(jié)旁正常組織中ERα水平[17.34(12.05 23.32)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.511,P0.001)。4.3甲狀腺組織中雌激素受體β(ERβ)水平男性結(jié)節(jié)組ERβ水平[13.85(11.61 23.85)ng/ml]高于結(jié)節(jié)旁正常組織中ERβ水平[9.62(6.94 11.44)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-3.58,P0.001)。絕經(jīng)前女性結(jié)節(jié)組ERβ水平[13.72(9.31 22.62)pg/ml]高于結(jié)節(jié)旁正常組織中ERβ水平[9.11(7.20 12.83)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.043,P0.001)。絕經(jīng)后女性結(jié)節(jié)組ERβ水平[15.25(8.85 47.44)pg/ml]高于結(jié)節(jié)旁正常組織中ERβ水平[8.75(5.33 13.78)pg/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.54,P0.001)。5甲狀腺結(jié)節(jié)患者甲狀腺組織中雄激素受體(AR)水平男性結(jié)節(jié)組AR水平[4.69(3.07 5.23)ng/ml]高于結(jié)節(jié)旁正常組織中AR水平[2.71(1.70 3.72)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-3.046,P=0.002)。絕經(jīng)前女性結(jié)節(jié)組AR水平[4.53(3.49 5.25)ng/ml]高于結(jié)節(jié)旁正常組織中AR水平[2.95(2.28 3.66)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.227,P0.001)。絕經(jīng)后女性結(jié)節(jié)組AR水平[4.75(3.19 5.69)ng/ml]高于結(jié)節(jié)旁正常組織中AR水平[2.99(2.07 3.95)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.818,P0.001)。6甲狀腺結(jié)節(jié)患者甲狀腺組織中維生素D受體(VDR)水平男性結(jié)節(jié)組VDR水平[2.58(2.24 3.46)ng/ml]低于結(jié)節(jié)旁正常組織中VDR水平[4.27(3.64 8.40)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-3.576,P0.001)。絕經(jīng)前女性結(jié)節(jié)組VDR水平[2.66(1.91 3.00)ng/ml]低于于結(jié)節(jié)旁正常組織中VDR水平[4.30(3.41 10.41)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-4.503,P0.001)。絕經(jīng)后女性結(jié)節(jié)組VDR水平[2.61(2.21 3.83)ng/ml]低于結(jié)節(jié)旁正常組織中VDR水平[4.44(3.37 12.52)ng/ml],兩者差異有統(tǒng)計(jì)學(xué)意義(Z=-5.153,P0.001)。結(jié)論:1甲狀腺結(jié)節(jié)局部的高E2水平以及高ERα和ERβ水平與結(jié)節(jié)的發(fā)生有關(guān)。2甲狀腺結(jié)節(jié)局部的高AR水平可能與甲狀腺結(jié)節(jié)的形成有關(guān)。3維生素D的缺乏以及甲狀腺結(jié)節(jié)局部的低VDR水平與甲狀腺結(jié)節(jié)的形成有關(guān)。
[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.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R581

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相關(guān)期刊論文 前1條

1 方枋;周柬;黃海玲;劉志民;;甲狀腺功能亢進(jìn)癥患者性激素受體改變及意義[J];第二軍醫(yī)大學(xué)學(xué)報(bào);2007年07期

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