Volume 37 Issue 5
Oct.  2013
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Significance of 131I whole body scan combined with serum thyroglobulin in the follow-up of differentiated hyroid cancer after thyroid ablation

  • Objective To evaluate the clinical value of 131I whole body scans with that of serum thyroglobulin(Tg)determination for the follow-up of differentiated thyroid carcinoma(DTC)receiving post-operative 131I therapy. Methods There were 153 patients with differentiated thyroid cancer receiving post-operative 131I therapy for more than one time at the dose of 1.85-9.25 GBq. Serum Tg levels were measured before 131I treatment and 131I whole body scans were performed 5 days after treatment. Results Among the 153 patients who underwent 131I therapy, serum Tg levels and 131I-whole body scans were both abnormal in 85 patients(55.6%). Both examinations were negative in 21 patients(13.7%). In the 19 patients with abnormal 131I whole body scans only, image study with means of 18F-FDG, SPECT, CT, ultrasonic or whole body bone scan revealed lesions in 13 patients; while in the 28 patients with abnormal Tg levels only, image study with the above means revealed lesions in 25 patients. The sensitivity of Tg positiveness and 131I whole body scans positiveness were 89%(110/123) and 79.6%(98/123) respectively, and the specificity were 90%(27/30)and 80%(24/30)respectively. Conclusions Routine serum Tg measurement and 131I whole body scans in patients with DTC with 131I radiotherapy after thyroidectomy is essential. It is of greatly clinical value in early detecting metastases, optimizing the 131I treatment protocol and evaluating the curative effect.
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  • [1] Kucukalić-Selimović E, Alagić J, Valjevac A, et al. The value of serum thyreoglobulin levels and whole body(I-131) scintigraphy in the follow-up of the thyroid cancer patients after thyroidectomy. Coll Antropol, 2012, 36 suppl 2: S67-71. doi: 10.1016/j.jchb.2012.09.003
    [2] Lind P. 131I whole body scintigraphy in thyroid cancer patients. Q J NucI Med, 1999, 43(3): 188-194.
    [3] Samuel AM, Rajashekharrao B, Shah DH. Pulmonary metastases in children and adolescents with well-differentiated thyroid cancer. J Nucl Med, 1998, 39(9): 1531-1536.
    [4] Zanotti-Fregonara P, Keller I, Rubello D, et al. Thyrotropin variations may explain some positive radioiodine therapy scans in patients with negative diagnostic scans. J Endocrinol Invest, 2009, 32(3): 267-271. doi: 10.1007/BF03346465
    [5] Alagić-Smailbegović J, Kucukalić-Selimović E, Setić I, et al. Importance of measurement of thyroglobulin and anti-thyroglobulin antibodies in differentiated thyroid cancer. Coll Antropol, 2012, 36 suppl 2: S33-38.
    [6] Fatourechi V, Hay ID. Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: including comments on the role of serum thyroglobulin monitoring in tumor surveillance. Semin Nucl Med, 2000, 30(2): 107 -114.
    [7] Dong MJ, Liu ZF, Zhao K, et al. Value of 18F-FDG-PET/PET-CT in differentiated thyroid carcinoma with radioiodine-negative whole-body scan: a meta-analysis. Nucl Med Commum, 2009, 30(8): 639-650. doi: 10.1097/MNM.0b013e32832dcfa7
    [8] Kunawudhi A, Pak-art R, Keelawat S, et al. Detection of subcentimeter metastatic cervical lymph node by 18F-FDG PET/CT in patients with well-differentiatedthyroid carcinoma and high serum thyroglobulin but negative 131I whole-body scan. Clin Nucl Med, 2012, 37(6): 561-567. doi: 10.1097/RLU.0b013e318252d30e
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Significance of 131I whole body scan combined with serum thyroglobulin in the follow-up of differentiated hyroid cancer after thyroid ablation

    Corresponding author: Jie SHEN, shenjie_vip@126.com
  • Department of Nuclear Medicine, Tianjin First Center Hospital, Tianjin 300192, China

Abstract:  Objective To evaluate the clinical value of 131I whole body scans with that of serum thyroglobulin(Tg)determination for the follow-up of differentiated thyroid carcinoma(DTC)receiving post-operative 131I therapy. Methods There were 153 patients with differentiated thyroid cancer receiving post-operative 131I therapy for more than one time at the dose of 1.85-9.25 GBq. Serum Tg levels were measured before 131I treatment and 131I whole body scans were performed 5 days after treatment. Results Among the 153 patients who underwent 131I therapy, serum Tg levels and 131I-whole body scans were both abnormal in 85 patients(55.6%). Both examinations were negative in 21 patients(13.7%). In the 19 patients with abnormal 131I whole body scans only, image study with means of 18F-FDG, SPECT, CT, ultrasonic or whole body bone scan revealed lesions in 13 patients; while in the 28 patients with abnormal Tg levels only, image study with the above means revealed lesions in 25 patients. The sensitivity of Tg positiveness and 131I whole body scans positiveness were 89%(110/123) and 79.6%(98/123) respectively, and the specificity were 90%(27/30)and 80%(24/30)respectively. Conclusions Routine serum Tg measurement and 131I whole body scans in patients with DTC with 131I radiotherapy after thyroidectomy is essential. It is of greatly clinical value in early detecting metastases, optimizing the 131I treatment protocol and evaluating the curative effect.

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  • 分化型甲状腺癌(differentiated thyroid carcinoma,DTC)经手术+131I治疗+甲状腺激素抑制治疗后,其主要随访方法为血清甲状腺球蛋白(thyroglobulin,Tg)水平测定和131I全身显像[1]。在临床工作中发现,两种检查的结果有不一致的现象,即131I全身显像阳性但Tg阴性和131I全身显像阴性但Tg阳性。且临床发现,给予患者较大治疗剂量的131I后全身显像能发现诊断剂量131I全身显像未能发现的转移或复发病灶。国外多数研究报道,诊断剂量131I全身显像灵敏度约为60.0%~70.4%,而131I治疗剂量全身显像的灵敏度高达75.0%~89.9%[2-3]。故我们对DTC术后患者血清Tg测定与治疗剂量的131I全身显像两种方法进行了对比研究,现报道如下。

1.   资料与方法

    1.1.   一般资料

  • 选择2008年12月至2011年5月在我院经手术病理确诊为DTC的患者153例,其中男性46例、女性107例,年龄8~82岁,DTC患者中乳头状癌患者140例、滤泡状癌患者13例,均在术后接受了1次以上的131I治疗,每次剂量为1.85~9.25 GBq,每次治疗前均测定血清Tg,治疗5 d后行前、后位131I全身显像。血清Tg与131I全身显像结果不一致的患者,进行其他影像学检查,如18F-FDG PET、SPECT、CT、全身骨显像或超声等,临床随访24~34个月,平均(29±7)个月,以确定结果。所有患者或患者家属均于131I治疗前签署了知情同意书。

  • 1.2.   血清Tg测定

  • 所有患者的血清Tg及甲状腺球蛋白抗体(thyroglobulin antibody,TgAb)均采用上海生物制品研究所提供的放射免疫测定试剂盒来测定,其检测灵敏度为1 ng/ml,判断标准:血清Tg > 10 ng/ml为阳性。检查前均停服甲状腺激素4~6周,且忌碘饮食30 d。

  • 1.3.   131I全身显像

  • 患者口服1.85~9.25 GBq治疗剂量131I(由原子高科股份有限公司提供)5 d后行全身显像,采用美国GE公司的高能准直器和Infinia Vc Hawkeye H3000Ys双探头符合线路SPECT仪作前、后位全身显像,矩阵256×256,扫描速度为20 cm/min,必要时加作局部或侧位显像。检查前禁服甲状腺激素及影响甲状腺吸碘功能的药物和食物4周。

  • 1.4.   结果分析

  • 所有患者血清Tg水平和131I全身显像的最终结果以最后一次的检测结果为准。因甲状腺癌患者有些部位的转移灶难以取得病理结果,患者的最终检查结果以随访的其他影像学检查结果为准(CT、超声、全身骨显像、MRI等)。

2.   结果
  • 153例DTC患者接受131I清除甲状腺残留后,共行血清Tg检查和131I全身显像检查各262次。随访中发现123例复发或转移者。153例患者中,55.6%(85/153)的患者血清Tg水平与131I全身显像结果均异常,13.7%(21/153)的患者两者均为正常,30.7%(47/153)的患者两者结果不一致(表 1)。经其他影像学检查证实,不一致的47例患者中,19例131I全身显像异常的患者中有13例证实复发或转移,28例血清Tg异常的患者中有25例证实复发或转移。所有患者血清Tg水平及TgAb水平如表 2所示。对最终结果分析得知,血清Tg诊断DTC复发或转移的灵敏度和特异度分别为89%(110/123)和90%(27/30),而131I全身显像的灵敏度和特异度分别为79.6%(98/123)和80%(24/30)。12.4%(19/153)经临床或者影像学检查证实有肺或(和)骨转移者,血清Tg水平升高很明显,甚至 > 700 ng/ml。

    Tg水平测定 131I全身显像 例数(%)
    - - 21(13.7%)
    + + 85(55.6%)
    + - 28(18.3%)
    - + 19(12.4%)
    注:表中,DTC:分化型甲状腺癌;Tg:甲状腺球蛋白。“+”表示血清Tg水平测定或131I全身显像结果为阳性,“-”表示结果为阴性。
    组别 例数 Tg(ng/ml) TgAb(IU/ml)
    无转移者 30 3.02±3.04 8.81±10.47
    复发或淋巴结转移者 101 81.68±75.26 10.54±10.73
    肺或(和)骨转移者 22 478.24±204.15 4.47±2.77
    注:表中,DTC:分化型甲状腺癌;Tg:甲状腺球蛋白;TgAb:甲状腺球蛋白抗体。
3.   讨论
  • DTC患者术后经131I清除甲状腺残留后,通过促甲状腺激素(30 mIU/L)刺激,80%患者的甲状腺具有摄碘功能。考虑到131I对甲状腺及甲状腺癌的“顿抑”效应,我们采用大剂量131I治疗后再进行全身显像更容易发现复发或转移灶,而且可以提高血清Tg预测肿瘤复发的准确率[4]131I去除剩余甲状腺组织后,血清中Tg理应完全消失或处于极低水平(< 1 ng/ml),如果随访发现血清Tg重新出现或升高,则是DTC复发或转移的特异性标志[5]。一般情况下血清Tg水平与131I全身显像结果应该一致,但在DTC随访过程中有少数患者出现不一致的现象。

    本研究中血清Tg水平与131I全身显像结果一致者为69.3%(106/153),但Tg的灵敏度和特异度高于131I全身显像。有复发或远处转移的患者血清Tg水平有相应的增高,有肺或(和)骨转移者,血清Tg水平升高更加明显,极端者甚至>700 ng/ml,反映此类患者血清Tg的合成与分泌较多。但此类患者在随访中发现随着131I治疗剂量的增加病灶缩小,其血清Tg水平亦随之降低。我们认为血清Tg水平是DTC术后随访的重要指标。

    本研究发现18.3%的患者血清Tg水平升高而131I全身显像阴性,但是文献报道有10%~15%的DTC患者Tg升高而131I全身显像阴性[6],本研究中该比例略高,这可能与以下因素有关:①转移灶与原发灶病理类型不一致;②如果转移灶与原发灶病理类型一致,但其分化程度可能更低,摄碘功能降低;③转移灶周围细胞遭到破坏,影响了转移灶对碘的摄取;④Tg合成和131I摄取率在不同的患者之间可能有所不同。12.4%的患者只有131I异常浓聚而无血清Tg水平的升高,这种结果的不一致性可能与以下原因有关:①DTC细胞钠碘泵的缺陷大于Tg合成与分泌的缺陷;②DTC复发灶或转移灶细胞分化比较差者有低水平血清Tg的倾向,合成释放的Tg量少,导致血清中Tg有低水平倾向;③血液中其他物质的干扰,如TgAb等[5]。这也许是某些DTC患者对131I治疗不敏感的部分原因。此外,体内激素或其他干扰因素也可导致Tg在低值区间波动而难以检出。

    总之,DTC术后及131I治疗后,常规进行血清Tg水平测定和131I全身显像检查,对术后判定复发转移及131I诊疗计划、评价131I疗效具有重要的临床应用价值,避免了单一检查所致的误诊或漏诊。PET/CT[7-8]、PET/MRI可作为这两种检查的补充,在随访中监测并定位诊断复发灶和转移灶。

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