消融前刺激性甲状腺球蛋白对分化型甲状腺癌合并结节性甲状腺肿复发或转移的诊断价值

doi:10.3969/j.issn.1674-8115.2021.05.009

摘要/Abstract

摘要：

目的·在分化型甲状腺癌（differentiated thyroid carcinoma，DTC）合并结节性甲状腺肿（nodular goitre，NG）患者中，评估术后碘消融前促甲状腺素（thyroid stimulating hormone，TSH）刺激性甲状腺球蛋白（preablative stimulated thyroglobulin，ps-Tg）作为早期预后指标的作用，确定ps-Tg预测该病复发或转移的最佳截断值。方法·回顾性分析接受甲状腺全切术和放射性 ¹³¹I 治疗的268例DTC合并NG患者的病例资料。采用Logistic回归分析评价ps-Tg和其他临床病理特征在术后早期阶段肿瘤远处转移中的预测意义。通过受试者操作特征（receiver operating characteristic，ROC）曲线分析，确定在DTC合并NG患者中ps-Tg预测复发或转移的最佳临界点。结果·Logistic分析结果显示，ps-Tg（OR=1.002，P=0.005）、N_1b（OR=0.235，P＝0.001）和组织病理类型（OR=0.263，P=0.012）是肿瘤远处转移的预测因子。ps-Tg预测疾病复发或转移的最佳截断值为26.97 ng/mL，敏感度和特异度分别为66.7%和83.3%，ROC曲线下面积为0.795。结论·对于DTC合并NG患者，ps-Tg、N_1b和组织病理类型对术后早期肿瘤复发或转移有重要预测意义；Ps-Tg的截断值有助于预测肿瘤的复发或转移。

关键词: 分化型甲状腺癌, 结节性甲状腺肿, 消融前刺激性甲状腺球蛋白

Abstract:

Objective·To evaluate the role of preablative stimulated thyroglobulin (ps-Tg) as an early prognostic marker for patients with differentiated thyroid carcinoma (DTC) complicated with nodular goitre (NG) after operation and determine the corresponding cut-off value.

Methods·A total of 268 patients with DTC complicated with NG who underwent the ¹³¹I treatment and thyroidectomy were analyzed. Logistic regression analysis were performed to evaluate baseline ps-Tg and other clinicopathologic characteristics in the prediction of distant metastasis. The receiver operating characteristic (ROC) curve analysis was conducted to analyze optimal cut-off point of ps-Tg for predicting the recurrence or metastasis for patients with DTC complicated with NG.

Results·In the Logistic analysis, ps-Tg (OR=1.002, P=0.005), N_1b (OR=0.235, P＝0.001) and the histological-pathological types (OR=0.263, P=0.012) were predictors of distant metastasis. The cut-off value of ps-Tg for predicting the recurrence or metastasis was 26.97 ng/mL, with sensitivity of 66.7% and specificity of 83.3%. Area under the ROC curve was 0.795.

Conclusion·For patients with DTC complicated with NG, ps-Tg, N_1b and the histological- pathological types have a significant prognostic implication in early postoperative metastasis or recurrence. The cut off value of ps-Tg could be more useful for the prediction of metastasis or recurrence.

Key words: differentiated thyroid carcinoma (DTC), nodular goitre (NG), preablative stimulated thyroglobulin (ps-Tg)

中图分类号:

R736.1

柴红, 黄琴, 陈泽泉, 杨佳欢, 余永利. 消融前刺激性甲状腺球蛋白对分化型甲状腺癌合并结节性甲状腺肿复发或转移的诊断价值[J]. 上海交通大学学报(医学版), 2021, 41(5): 617-621.

Hong CHAI, Qin HUANG, Ze-quan CHEN, Jia-huan YANG, Yong-li YU. Diagnostic value of preablative stimulated thyroglobulin for recurrence or metastases of differentiated thyroid carcinoma complicated with nodular goitre[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(5): 617-621.

图/表 3

参考文献 29

1	Wiltshire JJ, Drake TM, Uttley L, et al. Systematic review of trends in the incidence rates of thyroid cancer[J]. Thyroid, 2016, 26(11): 1541-1552.
2	Miller KD, Goding Sauer A, Ortiz AP, et al. Cancer statistics for hispanics/latinos, 2018[J]. CA Cancer J Clin, 2018, 68(6): 425-445.
3	Lim H, Devesa SS, Sosa JA, et al. Trends in thyroid cancer incidence and mortality in the United States, 1974-2013[J]. JAMA, 2017, 317(13): 1338-1348.
4	Raposo L, Morais S, Oliveira MJ, et al. Trends in thyroid cancer incidence and mortality in Portugal[J]. Eur J Cancer Prev, 2017, 26(2): 135-143.
5	Haugen BR, Alexander EK, Bible KC, et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer[J]. Thyroid, 2016, 26(1): 1-133.
6	Iqbal M, Mehmood Z, Rasul S, et al. Carcinoma thyroid in multi and uninodular goiter[J]. J Coll Physicians Surg Pak, 2010, 20(5): 310-312.
7	Edino ST, Mohammed AZ, Ochicha O, et al. Thyroid cancers in nodular goiters in Kano, Nigeria[J]. Niger J Clin Pract, 2010, 13(3): 298-300.
8	Karalus M, Tamatea JA, Conaglen HM, et al. Rates of unsuspected thyroid cancer in multinodular thyroid disease[J]. N Z Med J, 2018, 131(1468): 69-74.
9	Indrasena BSH. Use of thyroglobulin as a tumour marker[J]. World J Biol Chem, 2017, 8(1): 81-85.
10	Mutsuddy P, Jeon S, Yoo SW, et al. Optimization of serum thyroglobulin measured at different time points for prognostic evaluation in differentiated thyroid carcinoma patients[J]. Medicine, 2020, 99(14): e19652.
11	Kim MH, Ko SH, Bae JS, et al. Combination of initial stimulation thyroglobulins and staging system by revised ATA guidelines can elaborately discriminate prognosis of patients with differentiated thyroid carcinoma after high-dose remnant ablation[J]. Clin Nucl Med, 2012, 37(11): 1069-1074.
12	Baudin E, Do Cao C, Cailleux AF, et al. Positive predictive value of serum thyroglobulin levels, measured during the first year of follow-up after thyroid hormone withdrawal, in thyroid cancer patients[J]. J Clin Endocrinol Metab, 2003, 88(3): 1107-1111.
13	Hall FT, Beasley NJ, Eski SJ, et al. Predictive value of serum thyroglobulin after surgery for thyroid carcinoma[J]. Laryngoscope, 2003, 113(1): 77-81.
14	Piccardo A, Arecco F, Puntoni M, et al. Focus on high-risk DTC patients: high postoperative serum thyroglobulin level is a strong predictor of disease persistence and is associated to progression-free survival and overall survival[J]. Clin Nucl Med, 2013, 38(1): 18-24.
15	Ronga G, Filesi M, Ventroni G, et al. Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma[J]. Eur J Nucl Med, 1999, 26(11): 1448-1452.
16	Ciappuccini R, Hardouin J, Heutte N, et al. Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: the impact of treatment preparation modalities and tumor burden[J]. Eur J Endocrinol, 2014, 171(2): 247-252.
17	González C, Aulinas A, Colom C, et al. Thyroglobulin as early prognostic marker to predict remission at 18-24 months in differentiated thyroid carcinoma[J]. Clin Endocrinol (Oxf), 2014, 80(2): 301-306.
18	Webb RC, Howard RS, Stojadinovic A, et al. The utility of serum thyroglobulin measurement at the time of remnant ablation for predicting disease-free status in patients with differentiated thyroid cancer: a meta-analysis involving 3 947 patients[J]. J Clin Endocrinol Metab, 2012, 97(8): 2754-2763.
19	Prior-Sánchez I, Barrera Martín A, Moreno Ortega E, et al. Is a second recombinant human thyrotropin stimulation test useful? The value of postsurgical undetectable stimulated thyroglobulin level at the time of remnant ablation on clinical outcome[J]. Clin Endocrinol (Oxf), 2017, 86(1): 97-107.
20	Heemstra KA, Liu YY, Stokkel M, et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma[J]. Clin Endocrinol (Oxf), 2007, 66(1): 58-64.
21	刘新峰,李娇,赵腾,等.刺激性甲状腺球蛋白<10 ng/ml 的分化型甲状腺癌¹³¹I治疗后的临床转归[J]. 中国医学科学院学报, 2016, 38(1):88-92.
22	Orlov S, Salari F, Kashat L, et al. Post-operative stimulated thyroglobulin and neck ultrasound as personalized criteria for risk stratification and radioactive iodine selection in low- and intermediate-risk papillary thyroid cancer[J]. Endocrine, 2015, 50(1): 130-137.
23	Verkooijen RBT, Verburg FA, van Isselt JW, et al. The success rate of I-131 ablation in differentiated thyroid cancer: comparison of uptake-related and fixed-dose strategies[J]. Eur J Endocrinol, 2008,159(3): 301-307.
24	Melo M, Costa G, Ribeiro C, et al. Stimulated thyroglobulin at recombinant human TSH-aided ablation predicts disease-free status one year later[J]. J Clin Endocrinol Metab, 2013, 98(11): 4364-4372.
25	Corrales EP, Príncipe RM, Muro SL, et al. Incidental differentiated thyroid carcinoma is less prevalent in Graves' disease than in multinodular goiter[J]. Endocrinol Nutr, 2012, 59(3):169-173.
26	Xu L, Wang WB, Zhao YP, et al. Medullary thyroid carcinoma with nodular goiter carries an excellent prognosis[J]. J Surg Oncol, 2012, 106(2): 169-173.
27	Filipović A, Paunović I. Characteristics of thyroid carcinoma in Grave's disease Hashimoto's thyroiditis and nodular goiter[J]. Acta Chir Iugosl, 2003, 50(3): 135-139.
28	Kitahara CM, Farkas DKR, Jørgensen JOL, et al. Benign thyroid diseases and risk of thyroid cancer: a nationwide cohort study[J]. J Clin Endocrinol Metab, 2018,103(6): 2216-2224.
29	Veit F, Graf D, Momberger S, et al. Papillary thyroid cancer and coexisting autoimmune thyroiditis[J]. Horm Metab Res, 2017, 49(11): 869-872.

Item	NG with PTC (n=230)	NG with other types of DTC (n=38)	P value
Gender/% （n/n）
Female	71.30 (164/230)	63.16 (24/38)	1.034
Male	28.70 (66/230)	36.84 (14/38)	0.309
Age/years	46.02±13.45	47.08±15.30	0.659
TSH/(U·L^-1)	94.50±50.72	96.97±48.24	0.780
TgAb/(mIU·L^-1)	150.66±531.5	58.07±116.99	0.286
N stage/% （n/n）			0.000
N₀	29.13 (67/230)	63.16 (24/38)
N_1a	23.91 (55/230)	5.26 (2/38)
N_1b	26.96 (62/230)	21.05 (8/38)
N_1a+N_1b	20.00 (46/230)	10.53 (4/38)
TNM stage/% （n/n）			0.267
Ⅰ	49.13 (113/230)	34.21 (13/38)
Ⅱ	12.61 (29/230)	18.42 (7/38)
Ⅲ	10.87 (25/230)	18.42 (7/38)
Ⅳ	27.40 (63/230)	28.95 (11/38)
Risk stratification/% （n/n）			0.051
Low	56.52 (130/230)	42.11 (16/38)
Inter	22.17 (51/230)	18.42 (7/38)
High	21.30 (49/230)	39.47 (15/38)
Distant metastasis/% （n/n）			0.017
Yes	14.35 （33/230）	31.58 （12/38）
No	85.65 （197/230）	68.42 （26/38）

Item	NG with PTC (n=230)	NG with other types of DTC (n=38)	P value
Gender/% （n/n）
Female	71.30 (164/230)	63.16 (24/38)	1.034
Male	28.70 (66/230)	36.84 (14/38)	0.309
Age/years	46.02±13.45	47.08±15.30	0.659
TSH/(U·L^-1)	94.50±50.72	96.97±48.24	0.780
TgAb/(mIU·L^-1)	150.66±531.5	58.07±116.99	0.286
N stage/% （n/n）			0.000
N₀	29.13 (67/230)	63.16 (24/38)
N_1a	23.91 (55/230)	5.26 (2/38)
N_1b	26.96 (62/230)	21.05 (8/38)
N_1a+N_1b	20.00 (46/230)	10.53 (4/38)
TNM stage/% （n/n）			0.267
Ⅰ	49.13 (113/230)	34.21 (13/38)
Ⅱ	12.61 (29/230)	18.42 (7/38)
Ⅲ	10.87 (25/230)	18.42 (7/38)
Ⅳ	27.40 (63/230)	28.95 (11/38)
Risk stratification/% （n/n）			0.051
Low	56.52 (130/230)	42.11 (16/38)
Inter	22.17 (51/230)	18.42 (7/38)
High	21.30 (49/230)	39.47 (15/38)
Distant metastasis/% （n/n）			0.017
Yes	14.35 （33/230）	31.58 （12/38）
No	85.65 （197/230）	68.42 （26/38）

Variable	OR (95%CI)	P value
Gender	1.874 （0.732?4.805）	0.191
Age	0.794 （0.089?7.097）	0.837
T stage	1.864 （0.738?4.709）	0.188
Capsular invasion	0.915 （0.257?3.257）	0.891
Multifocality	1.232 （0.508?2.987）	0.644
Pathological type	0.263 （0.092?0.750）	0.012
TSH	0.995 （0.988?1.003）	0.256
TgAb	1.418 （0.578?3.479）	0.446
ps-Tg	1.002 （1.001?1.004）	0.005
N_1b	0.235 （0.099?0.559）	0.001

Variable	OR (95%CI)	P value
Gender	1.874 （0.732?4.805）	0.191
Age	0.794 （0.089?7.097）	0.837
T stage	1.864 （0.738?4.709）	0.188
Capsular invasion	0.915 （0.257?3.257）	0.891
Multifocality	1.232 （0.508?2.987）	0.644
Pathological type	0.263 （0.092?0.750）	0.012
TSH	0.995 （0.988?1.003）	0.256
TgAb	1.418 （0.578?3.479）	0.446
ps-Tg	1.002 （1.001?1.004）	0.005
N_1b	0.235 （0.099?0.559）	0.001

[1]	许飞，汤玲琳，袁红，宋少莉,黄钢. 分化型甲状腺癌患者碘治疗前肝功能、血脂及血常规水平变化[J]. 上海交通大学学报（医学版）, 2018, 38(6): 632-.
[2]	叶智轶，马超，傅宏亮，等. 18F-FDG PET/CT显像在131I全身显像阴性的分化型甲状腺癌中的应用价值[J]. 上海交通大学学报（医学版）, 2016, 36(01): 76-.
[3]	叶智轶，马超，王辉. 核素定位显像探查分化型甲状腺癌转移灶的临床研究[J]. 上海交通大学学报（医学版）, 2014, 34(1): 44-.
[4]	姚小芹, 王辉, 马超, 等. ¹⁸F-FDG符合线路显像在Tg阳性、¹³¹I显像阴性分化型甲状腺癌转移灶中的应用价值[J]. , 2013, 33(2): 174-.
[5]	程维维, 王辉, 冯方, 等. ¹⁸F-FDG PET/CT显像在¹³¹I全身扫描及血清Tg均阴性的已清除残留甲状腺组织的分化型甲状腺癌患者中的应用价值[J]. , 2012, 32(8): 1068-.
[6]	盛矢薇, 陆汉魁, 陈立波, 等. 分化型甲状腺癌合并甲状腺功能亢进症患者的临床特征及¹³¹I清除甲状腺残余组织的疗效[J]. , 2012, 32(1): 82-.
[7]	叶智轶, 傅宏亮, 李佳宁, 等. ¹³¹I-SPECT/CT融合显像对¹³¹I全身显像在分化型甲状腺癌诊治中的增益价值[J]. , 2011, 31(8): 1150-.
[8]	吴震宇, 王辉. 分化型甲状腺癌不同部位转移灶¹³¹I-SPECT/CT影像学数据分析[J]. , 2011, 31(8): 1154-.
[9]	邱忠领, 许艳红, 宋红俊, 等. 分化型甲状腺癌骨转移的临床特点及影像学诊断分析[J]. , 2010, 30(9): 1059-.
[10]	吴震宇, 陈素芸, 杜学良, 等. 分化型甲状腺癌术后或替代药物撤除后患者血清相关激素水平的变化研究[J]. , 2010, 30(6): 713-.
[11]	王磊, 钟竑, 张辅贤, 等. 巨大气管腺样囊性癌伴结节性甲状腺肿一例报道[J]. , 2010, 30(4): 485-.
[12]	傅宏亮, 杜学亮, 顾振辉, 等. 分化型甲状腺癌¹³¹I疗效影响因素分析[J]. , 2010, 30(3): 249-.
[13]	邹仁健, 傅宏亮, 吴靖川, 等. 分化型甲状腺癌¹³¹I治疗中多种核素显像的联合应用[J]. , 2010, 30(3): 256-.
[14]	冯方, 傅宏亮, 叶智轶, 等. 分化型甲状腺癌细胞株FTC-133失分化现象与¹³¹I辐射的关系[J]. , 2010, 30(3): 259-.
[15]	叶智轶, 傅宏亮, 李佳宁, 等. 儿童和青少年分化型甲状腺癌¹³¹I治疗分析[J]. , 2010, 30(3): 264-.