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甲状腺结节是颈部最常见的肿块性疾病之一,女性、老年人、碘缺乏地区及接受头颈部放射性治疗的群体患病率更高[1]。欧美国家普通人群中的甲状腺结节超声检出率为20%~70%[2-3],国内为18.6%,其中5%~15%为甲状腺癌[1, 4],且有增高趋势[5]。在甲状腺结节的诊断和治疗过程中,常因无法明确肿物的性质而使治疗处于两难境地。甲状腺癌起病隐匿且生物学特征多变,影像学、细胞学及临床特征与良性病变存在较多交叉,使现有的术前甲状腺结节良恶性的评价方法存在一定的误诊率。目前术前判断甲状腺结节的良恶性主要依靠甲状腺超声检查和细针穿刺细胞学(fine-needle aspiration cytology,FNAC)检查。其中常规超声(二维及多普勒超声)作为一种非侵入性检查方法,因其无创、简便易行、费用低廉等优点已被临床广泛应用,成为甲状腺结节性疾病的首选筛查方法。近年来,诸多文献显示甲状腺相关实验室检查指标,如血清甲状腺球蛋白(thyroglobulin,Tg)、抗甲状腺球蛋白抗体(antithyroglobulin antibody,TgAb)和TSH水平与甲状腺癌关系密切。本研究旨在分析分化型甲状腺癌和良性结节性甲状腺疾病中Tg、TgAb及TSH水平的分布规律及差异,并结合常规超声特征探讨其对甲状腺结节良、恶性病变的潜在预测价值。
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纳入分析的122例患者中,术前血清Tg阳性者55例(45.1%),阳性患者中24例合并甲状腺癌(19.67%);血清TSH升高者12例(9.8%),其中9例为甲状腺癌患者(7.4%)。甲状腺良恶性结节患者术前血清Tg和TSH水平测定结果见表 1。采用Wilcoxon秩和检验比较良性组和恶性组的Tg水平差异无统计学意义(Z=-1.292,P > 0.05),两组TSH水平的差异有统计学意义(Z=-2.107,P < 0.05)。
组别 例数 血清Tg(ng/ml) 血清TSH(mIU/L) 中位数 四分位数间距 中位数 四分位数间距 良性组 67 23.37 112.14 1.75 1.22 恶性组 55 24.09 64.59 2.32 2.28 表 1 甲状腺良恶性结节患者术前血清Tg和TSH水平测定结果
Table 1. Preoperative serum thyroglobulin and TSH level determination results in patients with benign and malignant thyroid nodules
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甲状腺良恶性结节患者的术前血清Tg和TgAb的分布情况见表 2。采用χ2检验比较,得出甲状腺结节良性组与恶性组Tg的阳性率差异无统计学意义(χ2=0.085,P > 0.05);两组间TgAb的阳性率差异有统计学意义(χ2=4.545,P < 0.05);良性组和恶性组Tg联合TgAb[即Tg和(或TgAb)]的阳性率差异有统计学意义(χ2=3.975,P < 0.05)。良性甲状腺结节和甲状腺癌中Tg和TgAb同时增高的例数分别为3例和2例。
组别 例数 血清Tg 血清TgAb Tg联合TgAb 阳性 阴性 阳性 阴性 阳性 阴性 良性组 67 31 36 9 58 37 30 恶性组 55 24 31 18 37 40 15 表中,Tg:甲状腺球蛋白;TgAb:抗甲状腺球蛋白抗体;Tg联合TgAb阳性组为Tg阳性和(或)TgAb阳性,阴性组为Tg和TgAb均为阴性。 表 2 甲状腺良恶性结节患者的术前血清Tg和TgAb的阳性例数
Table 2. Positive cases of preoperative serum thyroglobulin and antithyroglobulin antibody in patients with benign and malignant thyroid nodules
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对Tg、TgAb及TSH等血清指标与甲状腺癌的相关风险分别进行Logistic回归分析,结果示血清Tg抗体阳性、血清TSH升高是甲状腺癌的危险因素(表 3、图 1)。血清Tg水平与甲状腺癌的相关性不显著,考虑到TgAb对Tg的影响,将二者联合起来统计分析,得出Tg和TgAb阴性与甲状腺癌的风险呈负相关(表 3)。
图 1 不同 TSH 水平的甲状腺癌和甲状腺良性结节比例
Figure 1. The proportion of cases with thyroid cancer and benign thy-roid nodules in different TSH levels
变量 x2 P值 95%CI Tg 升高 - - 1 不高 0.065 0.799 1.097(0.537耀2.243) TgAb 阳性 - - 1 阴性 6.190 0.013▲ 0.319(0.130耀0.785) Tg联合TgAb 阳性 - - 1 阴性 4.130 0.042▲ 0.447(0.206耀0.972) TSH(mIU/L) >5.00 - - 1 < 0.34 0.494 0.482 0.333(0.016耀7.140) 0.34~2.49 5.447 0.020▲ 0.194(0.049耀0.769) 2.50~5.00 0.582 0.446 0.542(0.112耀2.619) 注:表中,Tg:甲状腺球蛋白;TgAb:抗甲状腺球蛋白抗体;95%CI:95%可信区间。▲表示差异具有统计学意义;“-”表示其以下的P值是与其所在行变量比较得出。 表 3 Tg、TgAb及TSH与甲状腺癌相关性的Logistic回归分析
Table 3. Logistic regression analysis of correlation between thyroid cancer and thyroglobulin, antithyroglobulin anti- body and TSH
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TSH的ROC显示曲线下面积(area under the curve,AUC)为0.611[95%可信区间(95%CI):0.509~0.713],P < 0.05。约登指数最大时,TSH取最佳临界值2.31 mIU/L,灵敏度和特异度分别为71.6%和50.9%;TSH : Tg的ROC显示AUC为0.617(95%CI:0.518~0.716),P < 0.05,最佳临界TSH : Tg值为0.11 IU/mg,灵敏度和特异度分别为61.2%和50.9%;Tg的ROC显示AUC < 0.5,故单独Tg因素对甲状腺癌的预测价值不太理想(图 2)。
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纳入分析的122例患者中,低回声型62例(50.8%),其中甲状腺癌44例(36.1%);等回声或高回声型60例(49.2%),其中甲状腺癌10例(8.2%);伴钙化者47例(38.5%),其中甲状腺癌37例(30.3%);囊性结节者6例,均为良性;实性结节者47例(38.5%),其中31例(25.4%)为甲状腺癌;囊实性69例(56.6%),其中24例(19.7%)为甲状腺癌;结节内部及周边无或仅见少量血流者60例(49.2%),其中29例(23.8%)为甲状腺癌;结节内部无或少量血流而周边可见丰富血流信号者28例(23.0%),其中4例(3.1%)为甲状腺癌;结节内部及周边均可见丰富血流信号者34例(27.9%),其中22例(18.0%)为甲状腺癌。
变量 x2 P值 95%CI 是否伴钙化 是 - - 1 否 30.264 0.085(0.036耀0.205) < 0.001▲ 0.085(0.036-0.205) 结节性质 囊实性 - - 1 实性 10.489 0.001▲ 3.633(1.664耀7.930) 结节血流 内有 - - 1 内周无 2.315 0.128 0.510(0.214耀1.214) 内无周有 13.675 < 0.001▲ 0.091(0.026耀0.324) 结节是否 是 - - 1 低回声 否 30.070 < 0.001▲ 0.092(0.039耀0.216) 注:表中,结节血流内有表示结节内部有丰富血流信号而结节周边有或无血流,内周无表示结节内部及周边均无明显血流信号,内无周有为结节内部无,周边有丰富血流信号;▲表示差异具有统计学意义;“-”表示其以下的χ2与P值是与其所在行变量比较得出。 表 4 甲状腺超声检查征象相关危险因素的Logistic回归分析
Table 4. Logistic regression analysis of related risk factors of thyroid cancer in ultrasound
Tg、TgAb及TSH在分化型甲状腺癌术前的预测分析
The prediction of risk of differentiated thyroid carcinoma with preoperative serum thyroid stimulating hormone, thyroglobulin and antithyroglobulin antibody
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摘要:
目的 探讨患者术前血清促甲状腺激素、甲状腺球蛋白(Tg)、抗甲状腺球蛋白抗体(TgAb)浓度在预测甲状腺癌中的价值。 方法 对122例接受手术治疗的甲状腺结节患者进行术前研究,以术后病理结果作为甲状腺结节性质的诊断金标准进行对照,其中分化型甲状腺癌55例,良性结节67例。采用化学发光法测定Tg和TSH;放射免疫分析法测定TgAb;采用彩色多普勒超声诊断仪检查甲状腺组织和颈部淋巴结。 结果 甲状腺癌组的术前血清Tg水平(24.09±64.59)ng/ml和甲状腺良性结节组(23.37±112.14)ng/ml间的差异无统计学意义(Z=-1.092,P > 0.05);甲状腺癌组的TSH水平(2.32±2.28)mIU/L高于甲状腺良性结节组(1.75±1.22)mIU/L,(Z=-2.107,P < 0.05);甲状腺癌组Tg联合TgAb的阳性率(72.7%)高于甲状腺良性结节组(55.2%)(χ2=3.975,P < 0.05)。各指标预测甲状腺癌的受试者工作特征曲线示,TSH值的曲线下面积(AUC)为0.611[95%可信区间(95%CI):0.509~0.713],P < 0.05,最佳临界值2.31 mIU/L,灵敏度和特异度分别为71.6%和50.9%;TSH : Tg值的AUC为0.617(95%CI:0.518~0.716),P < 0.05,最佳临界TSH : Tg值为0.11 IU/mg,灵敏度和特异度分别为61.2%和50.9%;Tg曲线AUC < 0.5。 结论 术前血清Tg的异常升高不是甲状腺癌的独立预测因素,但其结合TgAb阳性、TSH:Tg值>0.11 IU/mg可作为甲状腺癌的危险预测因素,可能是甲状腺超声检查的一种有效补充诊断手段。 Abstract:Objective To explore the values of preoperative serum thyroid stimulating hormone, thyroglobulin and antithyroglobulin antibody in predicting the risk of differentiated thyroid carcinoma. Methods 122 patients with thyroid nodules who got operations were studied, among which 55 patients with differentiated thyroid carcinoma(54 papillary and 1 follicular), 67 cases with benign thyroid nodules(40 nodular goiter and 27 adenoma). Serum thyroid-stimulating hormone(TSH) and thyroglobulin(Tg)were measured by chemiluminescence method, and antithyroglobulin antibody(TgAb) by radioimmunoassay. Thyroid tissues and cervical lymph nodes were checked using color doppler ultrasonic diagnostic instrument and the postoperative pathological results was regard as the gold standard of diagnosing thyroid cancer. Results Preoperative serum Tg levels in thyroid cancer group(24.09±64.59)ng/ml and benign thyroid nodules group(23.37±112.14) ng/ml had no statistical differences(Z=1.092, P > 0.05). TSH levels in thyroid carcinoma group(2.32±2.28) mIU/L were higher than that in benign thyroid nodules group(1.75±1.22) mIU/L(Z=2.107, P < 0.05). The positive rate of Tg combined with TgAb in thyroid cancer group(72.7%) was higher than that in benign thyroid nodules group(55.2%)(χ2= 3.975, P < 0.05). Receiver operating characteristic(ROC) curves showing sensitivity as a function of specificity were calculated for TSH, Tg levels and TSH : Tg values to evaluate the potential accuracy of the three index as predicting differentiated thyroid carcinoma. The area under the curve(AUC) of TSH was 0.611[95% confidence interval(95% CI):0.509~0.713], P < 0.05. The optimum threshold in ROC curves of TSH was 2.31 mIU/L. The sensitivity and specificity of TSH were 71.6% and 50.9% respectively. The AUC of TSH : Tg values was 0.617(95% CI:0.518~0.716), P < 0.05. The best critical value of TSH : Tg was 0.11 IU/mg. The sensitivity and specificity of TSH : Tg were 61.2% and 50.9% respectively. The AUC of Tg was less than 0.5. Conclusion Serum thyroglobulin elevated abnormally is not an independent predicting factor of differentiated thyroid cancer. The elevated Tg levels and/or positive TgAb and TSH : Tg > 0.11 IU/mg can be used as effective supplementary means of ultrasound examination in predicting differentiated thyroid carcinoma. -
表 1 甲状腺良恶性结节患者术前血清Tg和TSH水平测定结果
Table 1. Preoperative serum thyroglobulin and TSH level determination results in patients with benign and malignant thyroid nodules
组别 例数 血清Tg(ng/ml) 血清TSH(mIU/L) 中位数 四分位数间距 中位数 四分位数间距 良性组 67 23.37 112.14 1.75 1.22 恶性组 55 24.09 64.59 2.32 2.28 表 2 甲状腺良恶性结节患者的术前血清Tg和TgAb的阳性例数
Table 2. Positive cases of preoperative serum thyroglobulin and antithyroglobulin antibody in patients with benign and malignant thyroid nodules
组别 例数 血清Tg 血清TgAb Tg联合TgAb 阳性 阴性 阳性 阴性 阳性 阴性 良性组 67 31 36 9 58 37 30 恶性组 55 24 31 18 37 40 15 表中,Tg:甲状腺球蛋白;TgAb:抗甲状腺球蛋白抗体;Tg联合TgAb阳性组为Tg阳性和(或)TgAb阳性,阴性组为Tg和TgAb均为阴性。 表 3 Tg、TgAb及TSH与甲状腺癌相关性的Logistic回归分析
Table 3. Logistic regression analysis of correlation between thyroid cancer and thyroglobulin, antithyroglobulin anti- body and TSH
变量 x2 P值 95%CI Tg 升高 - - 1 不高 0.065 0.799 1.097(0.537耀2.243) TgAb 阳性 - - 1 阴性 6.190 0.013▲ 0.319(0.130耀0.785) Tg联合TgAb 阳性 - - 1 阴性 4.130 0.042▲ 0.447(0.206耀0.972) TSH(mIU/L) >5.00 - - 1 < 0.34 0.494 0.482 0.333(0.016耀7.140) 0.34~2.49 5.447 0.020▲ 0.194(0.049耀0.769) 2.50~5.00 0.582 0.446 0.542(0.112耀2.619) 注:表中,Tg:甲状腺球蛋白;TgAb:抗甲状腺球蛋白抗体;95%CI:95%可信区间。▲表示差异具有统计学意义;“-”表示其以下的P值是与其所在行变量比较得出。 表 4 甲状腺超声检查征象相关危险因素的Logistic回归分析
Table 4. Logistic regression analysis of related risk factors of thyroid cancer in ultrasound
变量 x2 P值 95%CI 是否伴钙化 是 - - 1 否 30.264 0.085(0.036耀0.205) < 0.001▲ 0.085(0.036-0.205) 结节性质 囊实性 - - 1 实性 10.489 0.001▲ 3.633(1.664耀7.930) 结节血流 内有 - - 1 内周无 2.315 0.128 0.510(0.214耀1.214) 内无周有 13.675 < 0.001▲ 0.091(0.026耀0.324) 结节是否 是 - - 1 低回声 否 30.070 < 0.001▲ 0.092(0.039耀0.216) 注:表中,结节血流内有表示结节内部有丰富血流信号而结节周边有或无血流,内周无表示结节内部及周边均无明显血流信号,内无周有为结节内部无,周边有丰富血流信号;▲表示差异具有统计学意义;“-”表示其以下的χ2与P值是与其所在行变量比较得出。 -
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