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131I治疗是DTC术后患者综合治疗的主要方法之一。在行首次131I治疗后,DTC术后患者唾液腺的摄取及排泌功能会受到不同程度的影响,其发生率为46%~78%[1-2]。国外大量研究结果表明,年龄、性别、131I治疗剂量、唾液腺疾病、TSH水平、身体质量指数(body mass index,BMI)、收缩压、舒张压、肿瘤分期、糖尿病史、淋巴结受累情况、131I全身扫描(whole body scan,WBS)结果、左甲状腺素钠片(levothyroxine sodium,L-T4)停药时间、DTC术后行131I治疗的时间等是DTC患者发生唾液腺损伤的危险因素[3-8]。目前,国内研究DTC患者术后行131I治疗发生唾液腺损伤的预测因素的文献报道非常有限。本研究中,我们回顾性分析107例接受首次131I治疗的DTC术后患者的临床资料,探讨131I治疗对唾液腺功能损伤的影响因素,旨在发现我国DTC术后131I治疗患者唾液腺功能损伤的危险因素。
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107例患者均为甲状腺乳头状癌,其中唾液腺正常患者70例,唾液腺损伤患者37例,唾液腺损伤发生率为34.6%(表1)。唾液腺正常患者和唾液腺损伤患者的唾液腺动态显像图分别见图2和图3。
因素 唾液腺损伤(n=37) 唾液腺正常(n=70) 检验值 P值 年龄(岁, )$\bar x \pm s $ 45.84±2.10 41.11±0.97 F=5.457 0.046 BMI( )$\bar x \pm s $ 22.02±1.35 24.71±0.43 F=5.556 0.064 收缩压(mm Hg, )$\bar x \pm s $ 127.59±3.10 119.86±1.84 F=5.210 0.024 舒张压(mm Hg, )$\bar x \pm s $ 83.06±1.82 82.01±1.24 F=0.231 0.632 糖尿病(例,%) − 0.657 有 1(2.7) 4(5.7) 无 36(97.3) 66(94.3) 组织病理学分型 − 1.000 乳头状癌 37(100) 70(100) 肿瘤分期 χ2=0.830 0.362 Ⅰ期 27(73.0) 45(64.3) Ⅱ期 10(27.0) 25(35.7) 淋巴结转移(例,%) − 0.769 有 29(78.4) 61(87.1) 无 8(21.6) 9(12.9) 131I治疗剂量(例,%) − 0.568 <3.7 GBq 0(0) 1(1.4) 3.7~5.6 GBq 34(91.9) 67(95.7) >5.6 GBq 3(8.1) 2(2.9) 131I治疗前TSH水平(mIU/L, )$\bar x \pm s $ 99.82±8.46 122.59±4.03 F=6.288 0.019 L-T4服用情况(例,%) χ2=1.613 0.204 停用1个月 18(48.6) 43(61.4) 未服用 19(51.4) 27(38.6) 术后月数(月, )$\bar x \pm s $ 1.94±0.18 2.25±0.21 F=0.899 0.345 131I WBS结果 − 0.543 阴性 0(0) 2(2.9) 阳性 37(100) 68(97.1) 注:−表示使用Fisher确切概率法,无检验值。BMI为身体质量指数;TSH为促甲状腺激素;L-T4为左甲状腺素钠片;WBS为全身扫描 表 1 107例分化型甲状腺癌患者131I治疗后影响唾液腺功能损伤的单因素分析
Table 1. Univariate analysis of factors affecting salivary gland function injury in 107 patients with differentiated thyroid cancer after 131I treatment
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单因素分析结果显示,患者的年龄、131I治疗前TSH水平、收缩压与DTC患者131I治疗后唾液腺功能损伤有关,唾液腺损伤患者的年龄、收缩压大于唾液腺正常患者,唾液腺损伤患者131I治疗前TSH水平低于唾液腺正常患者,且差异均有统计学意义(均P<0.05)(表1)。
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多因素Logistic 回归分析结果显示,年龄、131I治疗前TSH水平、收缩压是唾液腺功能损伤的非独立危险因素(均P>0.05)(表2)。
因素 B值 Wald值 OR值 95%CI P值 年龄 0.017 0.443 1.017 0.968~1.068 0.506 131I治疗前TSH水平 −0.011 3.771 0.989 0.979~1.000 0.052 收缩压 0.023 2.592 1.023 0.995~1.051 0.107 注:TSH为促甲状腺激素;OR为比值比;CI为置信区间 表 2 分化型甲状腺癌患者131I治疗后影响唾液腺功能损伤的多因素Logistic 回归分析
Table 2. Multivariate Logistic regression analysis of factors affecting salivary gland function injury in patients with differentiated thyroid cancer after 131I treatment
分化型甲状腺癌患者131I治疗后唾液腺损伤的相关因素分析
Analysis of related factors to salivary gland injury in patients with differentiated thyroid cancer after 131I treatment
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摘要:
目的 探讨分化型甲状腺癌(DTC)患者131I 治疗后唾液腺损伤的危险因素。 方法 回顾性分析2019年1月至2022年7月于山西医科大学第一医院行131I治疗的107例DTC患者的临床资料,其中男性35例、女性72例,年龄(42.8±1.0)岁。比较唾液腺损伤患者与唾液腺正常患者年龄、身体质量指数、收缩压、舒张压、原发肿瘤的组织病理学分型及分期、是否有淋巴结转移、是否并发糖尿病、131I治疗前促甲状腺素(TSH)水平、停用左甲状腺素钠片(L-T4)时间、131I治疗剂量、131I全身显像(WBS)等临床资料的差异。符合正态分布的计量资料的组间比较采用单因素方差分析(ANOVA),计数资料的组间比较采用χ2检验,期望频数<5时采用Fisher确切概率法。通过单因素分析和多因素Logistic回归分析明确唾液腺损伤的相关因素。 结果 107例DTC患者中,37例患者发生唾液腺损伤,唾液腺损伤的发生率为34.6%。单因素分析结果显示,唾液腺损伤患者的年龄、收缩压大于唾液腺正常患者[(45.84±2.10)岁 对(41.11±0.97)岁,(127.59±3.10) mm Hg对(119.86±1.84) mm Hg],唾液腺损伤患者131I治疗前TSH水平低于唾液腺正常患者[(99.82±8.46) mIU/L对(122.59±4.03) mIU/L],且差异有统计学意义(F=5.457、5.210、6.288,均P<0.05)。多因素Logistic回归分析结果显示,年龄、131I治疗前TSH水平、收缩压是唾液腺功能损伤的非独立危险因素(OR=1.017、0.989、1.023,均P>0.05)。 结论 年龄较大、131I治疗前TSH水平较低及收缩压较高是DTC患者行131I 治疗出现唾液腺损伤的相关因素。 Abstract:Objective To investigate the risk factors of salivary gland injury in patients with differentiated thyroid cancer (DTC) after 131I treatment. Methods The clinical data of 107 patients with DTC who received 131I treatment in the First Hospital of Shanxi Medical University from January 2019 to July 2022 were retrospectively analyzed. The patients included 35 males and 72 females, aged (42.8±1.0) years. The age, body mass index, systolic blood pressure, diastolic blood pressure, histopathological classification and stage of the primary tumor, lymph node metastasis, diabetes, thyroid stimulating hormone (TSH) level before 131I treatment, levothyroxine sodium discontinuation (L-T4) time, 131I treatment dose, 131I whole-body imaging, and other clinical data were compared between patients with salivary gland injury and those with normal salivary gland. Univariate analysis of variance was used to compare the measurement data conforming to normal distribution, and χ2 test was used to compare count data. Fisher's exact probability method was used when the expected frequency is less than 5. Univariate regression analyses and multivariate Logistic regression analyses were conducted to identify factors related to salivary gland injury. Results Among 107 DTC patients, 37 cases had salivary gland injury with an incidence of 34.6%. Univariate regression analysis showed that age and systolic blood pressure of patients with salivary gland injury were higher than those of patients with normal salivary gland ((45.84±2.10) years vs. (41.11±0.97) years, (127.59±3.10) mm Hg vs. (119.86±1.84) mm Hg); the TSH level before 131I treatment of patients with salivary gland injury was lower than that of patients with normal salivary gland ((99.82±8.46) mIU/L vs. (122.59±4.03) mIU/L), and the differences were statistically significant (F=5.457, 5.210, 6.288; all P<0.05). Multivariate Logistic regression analysis showed that age, TSH level before 131I treatment, and systolic blood pressure were independent risk factors for salivary gland injury (OR=1.017, 0.989, 1.023; all P>0.05). Conclusion Old age, low TSH level before 131I treatment, and high systolic blood pressure are related factors to salivary gland injury in patients with DTC after 131I treatment. -
Key words:
- Thyroid neoplasms /
- Iodion radioisotopes /
- Sialadenitis /
- Risk factors
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表 1 107例分化型甲状腺癌患者131I治疗后影响唾液腺功能损伤的单因素分析
Table 1. Univariate analysis of factors affecting salivary gland function injury in 107 patients with differentiated thyroid cancer after 131I treatment
因素 唾液腺损伤(n=37) 唾液腺正常(n=70) 检验值 P值 年龄(岁, )$\bar x \pm s $ 45.84±2.10 41.11±0.97 F=5.457 0.046 BMI( )$\bar x \pm s $ 22.02±1.35 24.71±0.43 F=5.556 0.064 收缩压(mm Hg, )$\bar x \pm s $ 127.59±3.10 119.86±1.84 F=5.210 0.024 舒张压(mm Hg, )$\bar x \pm s $ 83.06±1.82 82.01±1.24 F=0.231 0.632 糖尿病(例,%) − 0.657 有 1(2.7) 4(5.7) 无 36(97.3) 66(94.3) 组织病理学分型 − 1.000 乳头状癌 37(100) 70(100) 肿瘤分期 χ2=0.830 0.362 Ⅰ期 27(73.0) 45(64.3) Ⅱ期 10(27.0) 25(35.7) 淋巴结转移(例,%) − 0.769 有 29(78.4) 61(87.1) 无 8(21.6) 9(12.9) 131I治疗剂量(例,%) − 0.568 <3.7 GBq 0(0) 1(1.4) 3.7~5.6 GBq 34(91.9) 67(95.7) >5.6 GBq 3(8.1) 2(2.9) 131I治疗前TSH水平(mIU/L, )$\bar x \pm s $ 99.82±8.46 122.59±4.03 F=6.288 0.019 L-T4服用情况(例,%) χ2=1.613 0.204 停用1个月 18(48.6) 43(61.4) 未服用 19(51.4) 27(38.6) 术后月数(月, )$\bar x \pm s $ 1.94±0.18 2.25±0.21 F=0.899 0.345 131I WBS结果 − 0.543 阴性 0(0) 2(2.9) 阳性 37(100) 68(97.1) 注:−表示使用Fisher确切概率法,无检验值。BMI为身体质量指数;TSH为促甲状腺激素;L-T4为左甲状腺素钠片;WBS为全身扫描 表 2 分化型甲状腺癌患者131I治疗后影响唾液腺功能损伤的多因素Logistic 回归分析
Table 2. Multivariate Logistic regression analysis of factors affecting salivary gland function injury in patients with differentiated thyroid cancer after 131I treatment
因素 B值 Wald值 OR值 95%CI P值 年龄 0.017 0.443 1.017 0.968~1.068 0.506 131I治疗前TSH水平 −0.011 3.771 0.989 0.979~1.000 0.052 收缩压 0.023 2.592 1.023 0.995~1.051 0.107 注:TSH为促甲状腺激素;OR为比值比;CI为置信区间 -
[1] Krcalova E, Horacek J, Gabalec F, et al. Salivary gland function in thyroid cancer patients with radioiodine administration history[J]. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 2020, 164(3): 277−283. DOI: 10.5507/bp.2019.023. [2] Badam RK, Suram J, Babu DB, et al. Assessment of salivary gland function using salivary scintigraphy in pre and post radioactive iodine therapy in diagnosed thyroid carcinoma patients[J]. J Clin Diagn Res, 2016, 10(1): ZC60−ZC62. DOI: 10.7860/JCDR/2016/16091.7121. [3] Lee HN, An JY, Lee KM, et al. Salivary gland dysfunction after radioactive iodine (I-131) therapy in patients following total thyroidectomy: emphasis on radioactive iodine therapy dose[J]. Clin Imaging, 2015, 39(3): 396−400. DOI: 10.1016/j.clinimag.2014.12.018. [4] Riachy R, Ghazal N, Haidar MB, et al. Early sialadenitis after radioactive iodine therapy for differentiated thyroid cancer: prevalence and predictors[J]. Int J Endocrinol, 2020, 2020: 8649794. DOI: 10.1155/2020/8649794. [5] 梁昌平, 徐颖, 何涛. 131I治疗前不同撤药时间对分化型甲状腺癌患者甲状腺激素、血脂、心血管相关因素的影响及其临床分析[J]. 标记免疫分析与临床, 2022, 29(3): 408−412,437. DOI: 10.11748/bjmy.issn.1006-1703.2022.03.011.
Liang CP, Xu Y, He T. Effects of different withdrawal time points before 131I treatment on thyroid hormones, blood lipids and cardiovascular related factors in patients with differentiated thyroid carcinoma and its clinical analysis[J]. Labeled Immunoassays Clin Med, 2022, 29(3): 408−412,437. DOI: 10.11748/bjmy.issn.1006-1703.2022.03.011.[6] Hollingsworth B, Senter L, Zhang XL, et al. Risk factors of 131I-induced salivary gland damage in thyroid cancer patients[J]. J Clin Endocrinol Metab, 2016, 101(11): 4085−4093. DOI: 10.1210/jc.2016-1605. [7] Iakovou I, Goulis DG, Tsinaslanidou Z, et al. Effect of recombinant human thyroid-stimulating hormone or levothyroxine withdrawal on salivary gland dysfunction after radioactive iodine administration for thyroid remnant ablation[J]. Head Neck, 2016, 38(S1): SE227−E230. DOI: 10.1002/hed.23974. [8] Lee SM, Lee JW, Kim SY, et al. Prediction of risk for symptomatic sialadenitis by post-therapeutic dual 131I scintigraphy in patients with differentiated thyroid cancer[J]. Ann Nucl Med, 2013, 27(8): 700−709. DOI: 10.1007/s12149-013-0735-3. [9] 刘岩, 杨爱民, 欧阳雁, 等. 放射性核素唾液腺显像及抗核抗体联合检查在干燥综合征中的诊断价值[J]. 国际放射医学核医学杂志, 2014, 38(4): 219−222. DOI: 10.3760/cma.j.issn.1673-4114.2014.04.003.
Liu Y, Yang AM, Ouyang Y, et al. The diagnostic value of joint inspection of radionuclide salivary gland scintigraphy and antinuclear antibody examination in Sjögren's syndrome patients[J]. Int J Radiation Med Nucl Med, 2014, 38(4): 219−222. DOI: 10.3760/cma.j.issn.1673-4114.2014.04.003.[10] Byeon HK, Jeong GC, Kim B, et al. Clinical utility of quantitative parameters of salivary gland scintigraphy for diagnosing burning mouth syndrome[J/OL]. Diagnostics (Basel), 2022, 12(9): 2256[2022-10-10]. https://www.mdpi.com/2075-4418/12/9/2256. DOI: 10.3390/diagnostics12092256. [11] Upadhyaya A, Zhou PP, Meng ZW, et al. Radioprotective effect of vitamin E on salivary glands after radioiodine therapy for differentiated thyroid cancer: a randomized-controlled trial[J]. Nucl Med Commun, 2017, 38(11): 891−903. DOI: 10.1097/MNM.0000000000000727. [12] Almeida JP, Sanabria ÁE, Lima ENP, et al. Late side effects of radioactive iodine on salivary gland function in patients with thyroid cancer[J]. Head Neck, 2011, 33(5): 686−690. DOI: 10.1002/hed.21520. [13] 杨静, 郑容. 131I治疗分化型甲状腺癌肺转移患者的疗效及其影响因素[J]. 中国医学影像技术, 2016, 32(10): 1624−1627. DOI: 10.13929/j.1003-3289.2016.10.038.
Yang J, Zheng R. Curative effect and influencing factors of 131I in treatment of differentiated thyroid cancer patients with pulmonary metastases[J]. Chin Med Imaging Technol, 2016, 32(10): 1624−1627. DOI: 10.13929/j.1003-3289.2016.10.038.[14] Adramerinas M, Andreadis D, Vahtsevanos K, et al. Sialadenitis as a complication of radioiodine therapy in patients with thyroid cancer: where do we stand?[J]. Hormones (Athens), 2021, 20(4): 669−678. DOI: 10.1007/s42000-021-00304-3. [15] Dehbi HM, Mallick U, Wadsley J, et al. Recurrence after low-dose radioiodine ablation and recombinant human thyroid-stimulating hormone for differentiated thyroid cancer (HiLo): long-term results of an open-label, non-inferiority randomised controlled trial[J]. Lancet Diabetes Endocrinol, 2019, 7(1): 44−51. DOI: 10.1016/S2213-8587(18)30306-1. [16] Dong P, Qu Y, Yang L, et al. Outcomes after radioiodine ablation in patients with thyroid cancer: long-term follow-up of a Chinese randomized clinicaltrial[J]. Clin Endocrinol (Oxf), 2021, 95(5): 782−789. DOI: 10.1111/cen.14563. [17] Rosário PW, Borges MAR, Purisch S. Preparation with recombinant human thyroid-stimulating hormone for thyroid remnant ablation with 131I is associated with lowered radiotoxicity[J]. J Nucl Med, 2008, 49(11): 1776−1782. DOI: 10.2967/jnumed.108.050591. [18] Shen FC, Hsieh CJ, Huang IC, et al. Dynamic risk estimates of outcome in Chinese patients with well-differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation[J]. Thyroid, 2017, 27(4): 531−536. DOI: 10.1089/thy.2016.0479. [19] Ahn J, Jin MH, Song EY, et al. Clinical outcomes after early and delayed radioiodine remnant ablation in patients with low-risk papillary thyroid carcinoma: propensity score matching analysis[J]. Endocrinol Metab (Seoul), 2020, 35(4): 830−837. DOI: 10.3803/EnM.2020.747. [20] Cheng F, Xiao J, Huang FY, et al. Delay of initial radioactive iodine therapy beyond 3 months has no effect on clinical responses and overall survival in patients with thyroid carcinoma: a cohort study and a meta-analysis[J/OL]. Cancer Med, 2022, 11(12): 2386−2396[2022-10-10]. https://onlinelibrary.wiley.com/doi/10.1002/cam4.4607. DOI: 10.1002/cam4.4607. [21] Li H, Zhang YQ, Wang C, et al. Delayed initial radioiodine therapy related to incomplete response in low- to intermediate-risk differentiated thyroid cancer[J]. Clin Endocrinol (Oxf), 2018, 88(4): 601−606. DOI: 10.1111/cen.13551. [22] 王鑫, 宋清斌, 徐冬冬, 等. 术后首次放射性碘治疗时机的选择对分化型甲状腺癌早期疗效的影响[J]. 中国医科大学学报, 2019, 48(4): 359−362, 369. DOI: 10.12007/j.issn.0258-4646.2019.04.016.
Wang X, Song QB, Xu DD, et al. Effects of timing of initial postoperative radioactive iodine therapy on the outcome of patients with differentiated thyroid cancer[J]. J China Med Univ, 2019, 48(4): 359−362, 369. DOI: 10.12007/j.issn.0258-4646.2019.04.016.[23] 仝慧敏, 杨素云, 程艳. 131I致分化型甲状腺癌患者唾液腺辐射损伤及其防治的研究进展[J]. 国际放射医学核医学杂志, 2022, 46(7): 425−429. DOI: 10.3760/cma.j.cn121381-202111007-00198.
Tong HM, Yang SY, Cheng Y. Research progress on radiation injury of salivary gland and its prevention and treatment in patients with differentiated thyroid cancer induced by 131I[J]. Int J Radiat Med Nucl Med, 2022, 46(7): 425−429. DOI: 10.3760/cma.j.cn121381-202111007-00198.[24] Giontella A, Lotta LA, Overton JD, et al. Association of thyroid function with blood pressure and cardiovascular disease: a mendelian randomization[J/OL]. J Pers Med, 2021, 11(12): 1306[2022-10-10]. https://www.mdpi.com/2075-4426/11/12/1306. DOI: 10.3390/jpm11121306. [25] Goswami B, Bhattacharjya H, Sengupta S, et al. Hypovitaminosis D, dyslipidemia, and thyroid dysfunction among adolescents and their associations with blood pressure in a northeastern city of India[J]. Indian J Community Med, 2021, 46(3): 484−488. DOI: 10.4103/ijcm.IJCM_907_20.