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Graves甲状腺功能亢进症(简称甲亢)是最常见的甲状腺自身免疫性甲状腺毒症(thyrotoxicosis)。Graves甲亢需要与甲状腺炎导致的破坏性的甲状腺毒症进行鉴别,后者主要包括亚急性甲状腺炎(subacute thyroiditis)、无痛性甲状腺炎(painless thyroiditis,PT)和产后甲状腺炎(postpartum thyroiditis)。二者鉴别的临床意义在于治疗方案的不同,前者的治疗方法包括抗甲状腺药物治疗、131I治疗和手术治疗,后者以对症治疗或给予糖皮质激素治疗为主[1-3]。临床上PT并不少见,占甲状腺毒症的9%~23%;PT可以发生在Graves甲亢治疗后的缓解期,而多次反复发作的PT缓解后也可以出现Graves甲亢。目前,最佳的鉴别诊断方法是甲状腺摄131I率(radioactive iodine uptake,RAIU)测定或甲状腺静态显像。RAIU用于辅助诊断甲亢和甲状腺功能减退症(简称甲减),在体外利用甲状腺功能仪探测甲状腺吸收131I发射的γ射线,可以获得不同时间甲状腺部位的放射性计数,从而判定甲状腺的功能状态。甲状腺静态显像目前在临床上用于了解甲状腺的位置、形态、大小及功能状态,并可以辅助诊断及鉴别甲亢与甲状腺炎[4]。但这两项检查具有一定的辐射损伤性,因此存在一定的局限性[5-6]。
MRI弥散加权成像(diffusion-weighted imaging,DWI)是目前在活体上进行组织水分子弥散运动测量与成像的唯一方法。在DWI中,表观弥散系数(apparent diffusion coefficient,ADC)代表水分子移动的自由度,是反映水分子弥散的参数,ADC与组织的细胞密度呈负相关。早期对ADC的研究主要是在神经系统研究方面,目前更多地集中在肿瘤研究中,因为癌组织的细胞密度大、水分子弥散受限导致ADC降低。已经有研究证明ADC和反映肿瘤葡萄糖代谢的18F-FDG PET/CT的SUV是呈负相关的,这些研究也包括在头颈部肿瘤中的研究[7-9]。目前尚未见到使用ADC鉴别Graves甲亢与PT的报道。
本研究旨在通过前瞻性研究,探讨DWI、RAIU测定、甲状腺静态显像以及促甲状腺激素受体抗体(thyrotropin receptor antibody,TRAb)水平测定等在Graves甲亢与PT鉴别中的价值。
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Graves甲亢患者与PT患者比较,前者的ADC、FT3、TRAb水平和RAIU显著高于后者(t=15.126、3.682、7.226和31.574,P均<0.01)(表 1)。ADC、TRAb水平和RAIU三者之间存在显著的正相关性,相关系数均在0.700以上(P<0.01)(表 2)。χ2检验显示不同性别对两种疾病的鉴别无显著影响(χ2=0.148,P>0.05)。
组别 例数 年龄 ADC FT3 FT4 TSH TRAb TgAb TPOAb RAIU FT3/FT4 Graves甲亢 102 37.971±13.856 2.212±0.209 15.555±6.507 68.868±31.608 0.007±0.008 9.378±6.877 317.001±718.324 444.047±389.482 66.358±11.799 0.237±0.045 无痛性甲状腺炎 37 35.054±12.326 1.508±0.318 11.336±4.111 54.598±22.049 0.008±0.016 1.123±1.472 415.379±630.150 464.341±337.990 3.678± 4.075 0.219±0.051 t值 1.128 15.126 3.682 2.529 -0.909 7.226 -0.736 -0.281 31.574 2.046 P值 >0.05 <0.01 <0.01 <0.05 >0.05 <0.01 >0.05 >0.05 <0.01 <0.05 注:表中,ADC:表观弥散系数;FT3:游离三碘甲状腺原氨酸;FT4:游离甲状腺素;TRAb:促甲状腺激素受体抗体;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体;RAIU:甲状腺摄131I率。 表 1 Graves甲状腺功能亢进症和无痛性甲状腺炎的各指标比较
(x±s) Table 1. Comparisons of differential parameters between Graves disease and painless thyroiditis
(x±s) 指标名称 ADC TRAb RAIU 年龄 0.009 -0.055 0.079 ADC - 0.777* 0.902* FT3 0.524* 0.730* 0.479* FT4 0.436* 0.652* 0.401* TSH -0.060 -0.055 -0.075 TRAb 0.777* - 0.731* TgAb -0.043 -0.037 -0.095 TpoAb 0.015 -0.252* -0.082 RAIU 0.902* 0.731* - FT3/FT4 0.031 -0.085 0.051 注:表中,ADC:表观弥散系数;FT3:游离三碘甲状腺原氨酸;FT4:游离甲状腺素;TRAb:促甲状腺激素受体抗体;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体;RAIU:甲状腺摄131I率;*表示P<0.01;“-”表示无此项数据。 表 2 各指标的Pearson相关性分析
Table 2. Pearson bivariate correlations among differential parameters
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由放射科医师目测MRI显像结果,Graves甲亢和PT的T1加权图像(图 1a、1b)和T2加权图像(图 1c、1d)的信号强度没有明显的差异;但DWI图像显示,Graves甲亢的ADC信号强度显著高于PT的信号强度(图 1e、1f)。甲状腺静态显像结果显示,Graves甲亢患者甲状腺对核素的摄取能力明显增高,而PT患者甲状腺对核素的摄取能力明显降低(图 2)。
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绘制各指标对鉴别诊断Graves甲亢和PT的ROC(图 3),可见各指标的曲线下面积由高到低的排序依次是:RAIU>ADC>TRAb(其值分别为1.000>0.980>0.925),且曲线下面积均高于0.900,说明这3个指标有很好的诊断价值。根据ROC获得切分点值、灵敏度、特异度、准确率、阳性预测值、阴性预测值(表 3),可见RAIU具有最好的诊断价值,当最佳切分点值确定为24.500%时,灵敏度、特异度、准确率、阳性预测值和阴性预测值均为100.00%;ADC比TRAb的诊断价值更高,当最佳切分点值分别确定为1.837×10-3 mm2/s和1.350 IU/ml时,前者的灵敏度、特异度、准确率、阳性预测值和阴性预测值均在89%~97%,而后者在70%~90%。
图 3 ADC、TRAb、RAIU鉴别Graves甲状腺功能亢进症和无痛性甲状腺炎的ROC曲线 图中,ADC:表观弥散系数;TRAb:促甲状腺激素受体抗体;RAIU:甲状腺摄131I率。
Figure 3. Receiver operating characteristic curves of ADC, TRAb and RAIU for differentiatial diagnosis between Graves disease and painless thyroiditis
指标名称 切分点值 灵敏度(%) 特异度(%) 准确率(%) 阳性预测值(%) 阴性预测值(%) ADC 1.837×10-3 mm2/s 96.078 91.892 95.000 97.059 89.474 TRAb 1.350 IU/ml 88.235 75.676 84.892 90.909 70.000 RAIU 24.500% 100 100 100 100 100 注:表中,ROC:受试者工作特征曲线;ADC:表观弥散系数;TRAb:促甲状腺激素受体抗体;RAIU:甲状腺摄131I率。 表 3 ROC分析各指标对Graves甲状腺功能亢进症和无痛性甲状腺炎的鉴别诊断价值
Table 3. Differentiation diagnostic values of differential parameters analyzed by receiver operating characteristic curves
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在102例Graves甲亢患者中,有18例接受抗甲状腺药物治疗、78例进行了131I治疗、6例接受手术治疗,病理组织从6例接受手术治疗的患者中获得。在37例PT患者中,对2例多次复发的患者取组织活检。病理组织学结果(图 4):Graves甲亢的镜下表现为滤泡增生,滤泡上皮细胞增生,滤泡上皮细胞形成一些乳头状突起突入滤泡腔,间质血管扩张、充血,可见淋巴细胞浸润;PT的镜下表现为滤泡明显破坏,有大量的淋巴细胞浸润及淋巴滤泡形成。二者比较,PT的细胞密度远大于Graves甲亢。
MRI弥散加权成像、甲状腺摄碘率和血清指标测定鉴别Graves甲状腺功能亢进症和无痛性甲状腺炎的研究
Differentiation between Graves disease and painless thyroiditis by diffusion-weighted imaging, thyroid radioactive iodine uptake and serum parameters measurement
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摘要:
目的 研究MRI弥散加权成像(DWI)的表观弥散系数(ADC)、甲状腺摄131I率(RAIU)和血清指标等在Graves甲状腺功能亢进症(简称甲亢)和无痛性甲状腺炎(PT)鉴别中的价值。 方法 选取102例Graves甲亢患者和37例PT患者入组。测定所有患者的血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、TSH、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb)和促甲状腺激素受体抗体(TRAb)水平。采用3.0T超导型MRI仪完成MRI检查,并获得ADC。测定甲状腺24 h RAIU,并进行甲状腺静态显像。Graves甲亢患者的病理组织从接受手术的患者中获取(6例),PT患者的病理组织从接受活检的患者中获取(2例)。采用Pearson检验明确各指标间的相关性,用受试者工作特征曲线(ROC)分析各项指标的诊断价值,确定各项指标的切分点值,并判断各项指标的诊断灵敏度、特异度、准确率、阳性预测值和阴性预测值。 结果 与PT患者比较,Graves甲亢患者的ADC、TRAb和RAIU显著升高(t=15.126、7.226和31.574,P均<0.01)。ADC、TRAb和RAIU之间存在显著的正相关性。ROC显示,RAIU、ADC和TRAb的曲线下面积大于0.900。其中,RAIU具有最好的诊断价值,当最佳切分点值确定为24.500%时,灵敏度、特异度、准确率、阳性预测值和阴性预测值均为100%。ADC比TRAb的诊断价值更高,当最佳切分点值分别确定为1.837×10-3 mm2/s和1.350 IU/ml时,ADC的上述统计指标分别为96.078%、91.892%、95.000 %、97.059 %和89.474 %,TRAb的上述统计指标分别为88.235%、75.676%、84.892%、90.909%和70.000%。病理组织学结果显示:Graves甲亢以滤泡增生、滤泡上皮细胞增生以及血管扩张和充血为主要表现;PT以淋巴细胞浸润、淋巴滤泡形成以及滤泡破坏为主要表现。 结论 对于Graves甲亢和PT的鉴别,RAIU、ADC和TRAb均有价值,RAIU最佳、ADC次之。ADC的显像原理是基于不同疾病细胞密度差异的病生理变化,而RAIU的测定原理是反映不同疾病对碘摄取能力差异的病生理变化。 Abstract:Objective To assess the value of apparent diffusion coefficient(ADC) in diffusion-weighted imaging(DWI), thyroid radioactive iodine uptake(RAIU)and serum parameters in differential diagnosis between Graves disease(GD)and painless thyroiditis(PT). Methods One hundred and two patients with GD and 37 patients with PT were enrolled. Serum thyroid hormones and antibodies were measured, including free triiodothyronine(FT3), free thyroxine(FT4), TSH, thyroid globulin antibody(TgAb), thyroid peroxidase antibody(TPOAb) and thyrotropin receptor antibody(TRAb). DWI was obtained with a 3.0 T MR scanner, and ADC values were calculated. 24 h later RAIU and thyroid scintigraphy were conducted. Tissue samples were obtained in GD patients(6 cases) after thyroidectomy and in PT patients(2 cases) after biopsy. Pearson bivariate correlation was made. Receiver operating characteristic curves(ROC) were drawn and diagnostic efficacies were determined. Optimal cut-off values were selected, and then sensitivity, specificity, accuracy, positive predictive value and negative predictive value were assessed. Results ADC, TRAb and RAIU were significantly higher in GD than in PT(t=15.126, 7.226 and 31.574, with all P < 0.01). And they were closely and positively correlated. ROC showed areas under the curves for RAIU, ADC and TRAb were higher than 0.900. RAIU was the best method to differentiate GD from PT. When cutoff value of RAIU was determined as 24.500 %, sensitivity, specificity, accuracy, positive predictive value and negative predictive value were all 100%. The above statistical data were 96.078%, 91.892%, 95.000%, 97.059% and 89.474% for ADC, and 88.235%, 75.676%, 84.892%, 90.909% and 70.000% for TRAb, when the optimal thresholds of 1.837×10-3 mm2/s and 1.350 IU/ml were determined respectively. ADC was better than TRAb. Histopathology results showed that for GD, follicle hyperplasia, follicular epithelial cells hyperplasia, hyper-vascularity and congestive perfusion were characteristic features; while for PT, massive lymphocytic infiltration with hyperplastic germinal center formation and follicle disruption were characteristic features. Conclusions RAIU, DWI and TRAb were all of diagnostic values for differentiation between GD and PT, RAIU was the best method and DWI followed. DWI has great potential for thyroid pathophysiological imaging because it reflects tissue cellularity differences between GD and PT. The principle for RAIU is that it reflects the iodine uptake changes in different diseases. -
表 1 Graves甲状腺功能亢进症和无痛性甲状腺炎的各指标比较
(x±s) Table 1. Comparisons of differential parameters between Graves disease and painless thyroiditis
(x±s) 组别 例数 年龄 ADC FT3 FT4 TSH TRAb TgAb TPOAb RAIU FT3/FT4 Graves甲亢 102 37.971±13.856 2.212±0.209 15.555±6.507 68.868±31.608 0.007±0.008 9.378±6.877 317.001±718.324 444.047±389.482 66.358±11.799 0.237±0.045 无痛性甲状腺炎 37 35.054±12.326 1.508±0.318 11.336±4.111 54.598±22.049 0.008±0.016 1.123±1.472 415.379±630.150 464.341±337.990 3.678± 4.075 0.219±0.051 t值 1.128 15.126 3.682 2.529 -0.909 7.226 -0.736 -0.281 31.574 2.046 P值 >0.05 <0.01 <0.01 <0.05 >0.05 <0.01 >0.05 >0.05 <0.01 <0.05 注:表中,ADC:表观弥散系数;FT3:游离三碘甲状腺原氨酸;FT4:游离甲状腺素;TRAb:促甲状腺激素受体抗体;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体;RAIU:甲状腺摄131I率。 表 2 各指标的Pearson相关性分析
Table 2. Pearson bivariate correlations among differential parameters
指标名称 ADC TRAb RAIU 年龄 0.009 -0.055 0.079 ADC - 0.777* 0.902* FT3 0.524* 0.730* 0.479* FT4 0.436* 0.652* 0.401* TSH -0.060 -0.055 -0.075 TRAb 0.777* - 0.731* TgAb -0.043 -0.037 -0.095 TpoAb 0.015 -0.252* -0.082 RAIU 0.902* 0.731* - FT3/FT4 0.031 -0.085 0.051 注:表中,ADC:表观弥散系数;FT3:游离三碘甲状腺原氨酸;FT4:游离甲状腺素;TRAb:促甲状腺激素受体抗体;TgAb:甲状腺球蛋白抗体;TPOAb:甲状腺过氧化物酶抗体;RAIU:甲状腺摄131I率;*表示P<0.01;“-”表示无此项数据。 表 3 ROC分析各指标对Graves甲状腺功能亢进症和无痛性甲状腺炎的鉴别诊断价值
Table 3. Differentiation diagnostic values of differential parameters analyzed by receiver operating characteristic curves
指标名称 切分点值 灵敏度(%) 特异度(%) 准确率(%) 阳性预测值(%) 阴性预测值(%) ADC 1.837×10-3 mm2/s 96.078 91.892 95.000 97.059 89.474 TRAb 1.350 IU/ml 88.235 75.676 84.892 90.909 70.000 RAIU 24.500% 100 100 100 100 100 注:表中,ROC:受试者工作特征曲线;ADC:表观弥散系数;TRAb:促甲状腺激素受体抗体;RAIU:甲状腺摄131I率。 -
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