超声造影结合定量分析法及血清TSH、Gal-3、CK-19诊断甲状腺微小乳头状癌的临床价值

Value of quantitative analysis by CEUS and serum TSH, Gal-3, and CK-19 in the diagnosis of papillary thyroid microcarcinoma

摘要:

目的 探讨超声造影（CEUS）结合定量分析法及血清促甲状腺激素（TSH）、半乳糖凝集素3（Gal-3）、细胞角蛋白（CK-19）诊断甲状腺微小乳头状癌（PTMC）的临床价值。方法 回顾性分析2019年4月—2022年4月于唐山市工人医院行手术治疗的128例甲状腺微小结节患者的临床资料，其中59例PTMC患者作为PTMC组，69例甲状腺肿伴乳头状增生患者作为良性组。两组患者入院后均接受CEUS检查，以化学发光免疫法检测血清TSH，以免疫组织化学SP法检测Gal-3、CK-19表达。比较两组CEUS特征（增强顺序、消退模式、增强模式、环形增强、达峰强度、均匀增强）及参数［灌注峰值（Peak）、达峰时间（TP）、灌注率（Shapness）、曲线下面积（AUC）］，比较两组血清TSH水平与Gal-3、CK19表达情况，通过受试者工作特征（ROC）曲线分析CEUS参数及血清TSH水平诊断PTMC的价值。最后以临床诊断结果为金标准，通过一致性分析Gal-3、CK-19单独及CEUS参数、TSH、Gal-3、CK-19联合诊断PTMC的效能。结果 PTMC组增强顺序向心性、消退模式快出、增强模式慢进、无环形增强、达峰强度低增强、无均匀增强占比高于良性组（P <0.05）。PTMC组Peak、AUC低于良性组（P <0.05）。PTMC组与良性组CEUS参数TP、Shapness比较，差异无统计学意义（P >0.05）。PTMC组血清TSH水平高于良性组（P <0.05）。PTMC组Gal-3、CK-19阳性检出率高于良性组（P <0.05）。ROC曲线结果显示，Peak、AUC、TSH诊断PTMC的敏感性为55.1%（95% CI：0.489，0.697）、63.8%（95% CI：0.608，0.761）、62.3%（95% CI：0.724，0.848），特异性分别为77.2%（95% CI：0.492，0.701）、74.6%（95% CI：0.610，0.788）、96.6%（95% CI：0.729，0.859），AUC分别为0.615（95% CI：0.517，0.713）、0.708（95% CI：0.618，0.798）、0.810（95% CI：0.733，0.887）。Gal-3诊断PTMC的敏感性为93.2%（55/59），特异性为94.2%（65/69），准确率为93.8%（120/128），K=0.874；CK19诊断PTMC的敏感性为91.5（54/59），特异性为89.9%（62/69），准确率为90.6%（116/128），K=0.812；CEUS参数联合TSH、Gal-3、CK-19联合诊断PTMC的敏感性为96.6%（57/59），特异性为97.1%（67/69），准确率为96.9%（124/128），K=0.937。结论 CEUS参数及TSH、Gal-3、CK-19均能用于PTMC的诊断，但经一致性分析证实各项指标联合诊断优于单一指标诊断，可获得更好的敏感性与特异性，值得临床医师关注。

Abstract:

Objective To investigate the value of quantitative analysis by contrast-enhanced ultrasound (CEUS) and serum thyroid stimulating hormone (TSH), galectin-3 (Gal-3), and cytokeratin-19 (CK-19) in the diagnosis of papillary thyroid microcarcinoma (PTMC).Methods Clinical data of 128 patients with thyroid micronodules who underwent surgical treatment in our hospital from April 2019 to April 2022 were retrospectively analyzed, among which 59 patients with PTMC were included in the PTMC group (n = 59), and 69 patients with goiter accompanied by papillary thyroid hyperplasia were included in the benign group (n = 69). Both groups of patients received CEUS after admission. The serum level of TSH was detected by chemiluminescence immunoassay, and the levels of Gal-3 and CK-19 were detected by immunohistochemistry with the streptavidin-peroxidase (SP) method. The CEUS characteristics (sequence of enhancement, washout pattern, enhancement pattern, ring enhancement, peak intensity, and uniform enhancement) and parameters [peak, time to peak (TP), sharpness, and area under the curve (AUC)] were compared between the two groups. Serum levels of TSH, Gal-3 and CK-19 were also compared between the two groups. The value of CEUS parameters and the serum level of TSH in the diagnosis of PTMC was analyzed by receiver operating characteristic (ROC) curve. The clinical diagnosis was set as the gold standard, and the efficacy of Gal-3 or CK-19 alone and that of the combination of CEUS parameters, TSH, Gal-3, and CK-19 in the diagnosis of PTMC were analyzed by agreement analysis.Results The proportions of centripetal enhancement, fast washout, slow enhancement, absence of ring enhancement, low enhancement at peak and absence of uniform enhancement in the PTMC group were higher than those in the benign group (P < 0.05). The peak and AUC in the PTMC group were lower than those in the benign group (P < 0.05). There was no difference in TP and sharpness between the PTMC group and the benign group (P > 0.05). The serum level of TSH in the PTMC group was higher than that in the benign group (P < 0.05). The positive rates of Gal-3 and CK-19 in the PTMC group were higher than those in the benign group (P < 0.05). As shown in the ROC curve analysis, the sensitivities of peak, AUC and the level of TSH for diagnosing PTMC were 55.1% (95% CI: 0.489, 0.697), 63.8% (95% CI: 0.608, 0.761), and 62.3% (95% CI: 0.724, 0.848), with the specificities being 77.2% (95% CI: 0.492, 0.701), 74.6% (95% CI: 0.610, 0.788), 96.6% (95% CI: 0.729, 0.859), and the areas under the ROC curves being 0.615 (95% CI: 0.517, 0.713), 0.708 (95% CI: 0.618, 0.798), 0.810 (95% CI: 0.733, 0.887), respectively. The sensitivity, specificity and accuracy of Gal-3 in diagnosing PTMC were 93.2% (55/59), 94.2% (65/69), and 93.8% (120/128) (K = 0.874), respectively. The sensitivity, specificity and accuracy of CK19 for the diagnosis of PTMC were 91.5% (54/59), 89.9% (62/69), and 90.6% (116/128) (K = 0.812), respectively. The sensitivity, specificity and accuracy of CEUS parameters combined with TSH, Gal-3 and CK19 in the diagnosis of PTMC were 96.6 (59/59), 97.1 (67/69), and 96.9 (124/128) (K = 0.937), respectively.Conclusions CEUS parameters and levels of TSH, Gal-3, and CK-19 can all be applied in the diagnosis of PTMC. However, the agreement analysis suggests that the diagnostic efficacy of the combination of all indicators is superior to that of any single indicator with higher sensitivity and specificity, which should be paid attention to among clinicians.