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甲状腺癌是头颈部最常见的恶性肿瘤,近几十年来,其发病率呈上升趋势[1]。其中,大部分为来源于滤泡上皮细胞的DTC,占新发病例的95%以上,主要包括乳头状甲状腺癌(papillary thyroid carcinoma,PTC)、滤泡状甲状腺癌和Hürthle细胞甲状腺癌[2]。多数甲状腺癌经规范治疗后预后良好,2018年美国SEER(Surveillance, Epidemiology, and End Results Program)数据库显示,甲状腺癌患者的5年生存率高达98.3%[3]。DTC的初始治疗方法为手术,接受甲状腺全切或近全切除术的中高危患者需采用131I治疗,以破坏术后残留甲状腺组织及清除手术无法切除的摄碘病灶,提高患者的无病生存率及总生存率。之后,患者在长期甲状腺激素抑制或替代治疗中,需定期复查甲状腺激素水平并监测甲状腺球蛋白(thyroglobulin,Tg)水平。
Tg是一种糖蛋白,由甲状腺滤泡细胞产生,理论上,在手术、放射性碘治疗或其他消融治疗清除所有甲状腺组织后,血清中应检测不到Tg,Tg水平通常在术后3~4周达到最低点[4]。因此,目前公认的清甲目的之一是排除残留甲状腺组织分泌的Tg对疾病监测的影响,从而提高Tg在随访中的特异性,以便早期发现残留或复发病灶。当Tg持续存在或水平升高需引起高度警惕,并积极通过影像学方法寻找可疑病灶。然而,甲状腺球蛋白抗体(thyroglobulin antibody,TgAb)会干扰血清Tg水平的测定,影响将Tg用作DTC肿瘤标志物在随访中的临床价值。此时,连续的TgAb水平的测量可作为长期监测DTC复发的替代指标[5]。2015年,美国甲状腺协会指南建议需隔6~12个月同时测量TgAb滴度和血清Tg水平[4]。我们主要围绕TgAb在DTC中的产生机制及其临床价值进行综述。
血清甲状腺球蛋白抗体在分化型甲状腺癌中的产生机制及其临床价值
The generation mechanism and clinical value of serum thyroglobulin antibody in differentiated thyroid carcinoma
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摘要: 近年来,分化型甲状腺癌(DTC)的发病率呈逐年上升趋势,大多数患者通过外科手术、放射性碘治疗和促甲状腺激素抑制治疗后的预后良好,可获得长期生存,但部分患者存在疾病的持续、复发及转移。甲状腺球蛋白(Tg)作为DTC全切或近全切除术后灵敏、简便的血清学肿瘤标志物,在患者长期随访中的定期监测极为重要。然而,在高达25%的DTC患者的血清中可检测出高水平甲状腺球蛋白抗体(TgAb),其存在会干扰Tg的测定,此时TgAb的变化趋势就成为判断疾病状态的替代指标。TgAb随时间推移呈下降趋势往往预示疾病好转,相反,TgAb持续升高可能是DTC复发的早期指标。笔者主要就TgAb在DTC患者中的产生机制及其与临床的相关性进行综述。Abstract: The incidence of differentiated thyroid carcinoma (DTC) has kept increasing over the recent decades, and most patients carry a good prognosis and long-term survival through surgery, radioactive iodine therapy, and thyroid-stimulating hormone suppression therapy, while some patients have persistent, recurrent or metastatic disease. Thyroglobulin (Tg) can be regarded as a sensitive and convenient biochemical tumor marker after total or near-total resection of DTC and radioiodine therapy. Regular monitoring of Tg and thyroglobulin antibody (TgAb) in the long-term follow-up of patients is of extreme importance for disease surveillance. However, high serum levels of TgAb can be detected in up to 25% of patients with DTC, which will interfere with the accuracy of Tg assay. During which, the trends of TgAb can be served as a surrogate indicator to reflect the tumor status. A falling TgAb trend over time often indicates the remission or improvement of the disease. On the contrary, a sustained rising TgAb trend may be an early indicator of recurrence or metastases of DTC. Herein, the authors mainly reviewed the possible mechanism TgAb production and its clinical relevance in DTC.
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