Value of serum thyroglobulin in diagnosis and monitoring of differentiated thyroid cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Zongping , WU Bo , KANG Jie , DENG Xianzhao , GUO Bomin ,  FAN Youben

Department of General Sugery, The Sixth People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, P.R.China;

Corresponding author：

FAN Youben, Email: fanyouben2006@163.com

Keywords：

thyroglobulin; differentiated thyroid cancer; diagnosis; monitoring; prognosis

DOI：

10.7507/1007-9424.201610046

Video：

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Objective To summarize the value of serum thyroglobulin (Tg) in diagnosis before surgery and monitoring after surgery for differentiated thyroid cancer (DTC). Methods By using the method of literature review, the literatures related to the diagnosis and monitoring value of serum Tg for DTC were studied. Results ① Serum thyroglobulin had a certain value in diagnosis of thyroid nodules, especially in follicular cancer or Hürthle cancer whose diagnosis undetermined by fine-needle aspiration biopsy (FNAB), and it was closely linked with the tumor’s size and distant metastasis of the DTC. ② Raise of serum Tg postoperatively was important for judging the recurrence and metastasis of DTC. However, how to establish an appropriate threshold of serum Tg, identify the differences of results for different measurement methods, make the accurate judgment for false positive and false negative, and combine with other imaging methods appropriately, needed our attention. Conclusion Serum Tg plays a very important role in diagnosis before surgery and monitoring after surgery of DTC, clinical doctors need pay high attention on it.

Citation： WANG Zongping, WU Bo, KANG Jie, DENG Xianzhao, GUO Bomin, FAN Youben. Value of serum thyroglobulin in diagnosis and monitoring of differentiated thyroid cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2017, 24(3): 391-395. doi: 10.7507/1007-9424.201610046 Copy

1.	Jung CK, Little MP, Lubin JH,et al. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab, 2014, 99(2): E276-E285.
2.	Bray F, Ferlay J, Laversanne M,et al. Cancer incidence in five continents: inclusion criteria, highlights from volume X and the global status of cancer registration. Int J Cancer, 2015, 137(9): 2060-2071.
3.	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: 33-38.
4.	Rosen JE, Stone MD. Contemporary diagnostic approach to the thyroid nodule. J Surg Oncol, 2006, 94(8): 649-661.
5.	Tuttle RM, Leboeuf R. Follow up approaches in thyroid cancer: a risk adapted paradigm. Endocrinol Metab Clin North Am, 2008, 37(2): 419-435.
6.	Feldt-Rasmussen U, Verburg FA, Luster M,et al. Thyroglobulin autoantibodies as surrogate biomarkers in the management of patients with differentiated thyroid carcinoma. Curr Med Chem, 2014, 21(32): 3687-3692.
7.	Alonso-Gordoa T, Díez JJ, Durán M,et al. Advances in thyroid cancer treatment: latest evidence and clinical potential. Ther Adv Med Oncol, 2015, 7(1): 22-38.
8.	Evans C, Tennant S, Perros P. Serum thyroglobulin in the monitoring of differentiated thyroid cancer. Scand J Clin Lab Invest Suppl, 2016, 245(21): S119-S123.
9.	李小毅. 甲状腺球蛋白在分化型甲状腺癌诊治中的作用. 中国普外基础与临床杂志, 2006, 13(3): 265-267.
10.	Spencer CA. Challenges of serum thyroglobulin (Tg) measurement in the presence of Tg autoantibodies. J Clin Endocrinol Metab, 2004, 89(8): 3702-3704.
11.	Spencer C, LoPresti J, Fatemi S. How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies. Curr Opin Endocrinol Diabetes Obes, 2014, 21(5): 394-404.
12.	Clark PM. Laboratory services for thyroglobulin and implications for monitoring of differentiated thyroid cancer. J Clin Pathol, 2009, 62(5): 402-406.
13.	余小华, 骆磊, 朱郧鹤, 等. 化学发光免疫分析法和放射免疫分析法检测血浆甲状腺球蛋白的结果对比分析. 标记免疫分析与临床, 2012, 19(1): 54-56.
14.	Trimboli P, Treglia G, Giovanella L. Preoperative measurement of serum thyroglobulin to predict malignancy in thyroid nodules: a systematic review. Horm Metab Res, 2015, 47(4): 247-252.
15.	Lee EK, Chung KW, Min HS,et al. Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. J Korean Med Sci, 2012, 27(9): 1014-1018.
16.	Petric R, Besic H, Besic N. Preoperative serum thyroglobulin concentration as a predictive factor of malignancy in small follicular and Hürthle cell neoplasms of the thyroid gland. World J Surg Oncol, 2014, 12: 282.
17.	Oltmann SC, Leverson G, Lin SH,et al. Markedly elevated thyroglobulin levels in the preoperative thyroidectomy patient correlates with metastatic burden. J Surg Res, 2014, 187(1): 1-5.
18.	刘安民, 王永梅, 李玥. 分析甲状腺球蛋白 (TG) 与分化型甲状腺癌转移灶的相关性及 TG 的诊断意义. 当代医学, 2015, 21(36): 43-44.
19.	Giovanella L, Clark PM, Chiovato L,et al. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper. Eur J Endocrinol, 2014, 171(2): R33-R46.
20.	Gurleyik E, Dogan S. Accuracy of unstimulated Basal serum thyroglobulin levels in assessing the completeness of thyroidectomy. J Clin Med Res, 2014, 6(5): 369-373.
21.	Yang X, Liang J, Li T,et al. Preablative stimulated thyroglobulin correlates to new therapy response system in differentiated thyroid cancer. J Clin Endocrinol Metab, 2016, 101(3): 1307-1313.
22.	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. Clin Nucl Med, 2013, 38(1): 18-24.
23.	Polachek A, Hirsch D, Tzvetov G,et al. Prognostic value of post-thyroidectomy thyroglobulin levels in patients with differentiated thyroid cancer. J Endocrinol Invest, 2011, 34(11): 855-860.
24.	Piccardo A, Arecco F, Morbelli S,et al. Low thyroglobulin concentrations after thyroidectomy increase the prognostic value of undetectable thyroglobulin levels on levo-thyroxine suppressive treatment in low-risk differentiated thyroid cancer. J Endocrinol Invest, 2010, 33(2): 83-87.
25.	Heemstra KA, Liu YY, Stokkel M,et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf), 2007, 66(1): 58-64.
26.	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. Clin Nucl Med, 2012, 37(11): 1069-1074.
27.	Krajewska J, Jarzab M, Czarniecka A,et al. Ongoing risk stratification for differentiated thyroid cancer (DTC)-stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients. Endokrynol Pol, 2016, 67(1): 2-11.
28.	Phan HT, Jager PL, van der Wal JE,et al. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol, 2008, 158(1): 77-83.
29.	David A, Blotta A, Bondanelli M,et al. Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone. J Nucl Med, 2001, 42(10): 1470-1475.
30.	Robenshtok E, Tuttle RM. Role of recombinant human thyrotropin (rhTSH) in the treatment of well-differentiated thyroid cancer. Indian J Surg Oncol, 2012, 3(3): 182-189.
31.	Zhao T, Liang J, Guo Z,et al. Serum thyrotropin level of 30 μIU/mL is inadequate for preablative thyroglobulin to serve as a prognostic marker for differentiated thyroid cancer. Endocrine, 2016, 53(1): 166-173.
32.	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 Clin Endocrinol Metab, 2012, 97(8): 2754-2763.
33.	Bertagna F, Albano D, Bosio G,et al.¹⁸F-FDG-PET/CT in patients affected by differentiated thyroid carcinoma with positive thyroglobulin level and negative¹³¹I whole body scan. It’s value confirmed by a bicentric experience. Curr Radiopharm, 2016, 9(36): 1022-1035.
34.	American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer; Cooper DS, Doherty GM,et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 2009, 19(11): 1167-1214.
35.	Özdemir E, Yildirim Poyraz N, Polat SB,et al. Diagnostic value of¹⁸F-FDG PET/CT in patients with TENIS syndrome: correlation with thyroglobulin levels. Ann Nucl Med, 2014, 28(3): 241-247.

1. Jung CK, Little MP, Lubin JH,et al. The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations. J Clin Endocrinol Metab, 2014, 99(2): E276-E285.
2. Bray F, Ferlay J, Laversanne M,et al. Cancer incidence in five continents: inclusion criteria, highlights from volume X and the global status of cancer registration. Int J Cancer, 2015, 137(9): 2060-2071.
3. 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: 33-38.
4. Rosen JE, Stone MD. Contemporary diagnostic approach to the thyroid nodule. J Surg Oncol, 2006, 94(8): 649-661.
5. Tuttle RM, Leboeuf R. Follow up approaches in thyroid cancer: a risk adapted paradigm. Endocrinol Metab Clin North Am, 2008, 37(2): 419-435.
6. Feldt-Rasmussen U, Verburg FA, Luster M,et al. Thyroglobulin autoantibodies as surrogate biomarkers in the management of patients with differentiated thyroid carcinoma. Curr Med Chem, 2014, 21(32): 3687-3692.
7. Alonso-Gordoa T, Díez JJ, Durán M,et al. Advances in thyroid cancer treatment: latest evidence and clinical potential. Ther Adv Med Oncol, 2015, 7(1): 22-38.
8. Evans C, Tennant S, Perros P. Serum thyroglobulin in the monitoring of differentiated thyroid cancer. Scand J Clin Lab Invest Suppl, 2016, 245(21): S119-S123.
9. 李小毅. 甲状腺球蛋白在分化型甲状腺癌诊治中的作用. 中国普外基础与临床杂志, 2006, 13(3): 265-267.
10. Spencer CA. Challenges of serum thyroglobulin (Tg) measurement in the presence of Tg autoantibodies. J Clin Endocrinol Metab, 2004, 89(8): 3702-3704.
11. Spencer C, LoPresti J, Fatemi S. How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies. Curr Opin Endocrinol Diabetes Obes, 2014, 21(5): 394-404.
12. Clark PM. Laboratory services for thyroglobulin and implications for monitoring of differentiated thyroid cancer. J Clin Pathol, 2009, 62(5): 402-406.
13. 余小华, 骆磊, 朱郧鹤, 等. 化学发光免疫分析法和放射免疫分析法检测血浆甲状腺球蛋白的结果对比分析. 标记免疫分析与临床, 2012, 19(1): 54-56.
14. Trimboli P, Treglia G, Giovanella L. Preoperative measurement of serum thyroglobulin to predict malignancy in thyroid nodules: a systematic review. Horm Metab Res, 2015, 47(4): 247-252.
15. Lee EK, Chung KW, Min HS,et al. Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules. J Korean Med Sci, 2012, 27(9): 1014-1018.
16. Petric R, Besic H, Besic N. Preoperative serum thyroglobulin concentration as a predictive factor of malignancy in small follicular and Hürthle cell neoplasms of the thyroid gland. World J Surg Oncol, 2014, 12: 282.
17. Oltmann SC, Leverson G, Lin SH,et al. Markedly elevated thyroglobulin levels in the preoperative thyroidectomy patient correlates with metastatic burden. J Surg Res, 2014, 187(1): 1-5.
18. 刘安民, 王永梅, 李玥. 分析甲状腺球蛋白 (TG) 与分化型甲状腺癌转移灶的相关性及 TG 的诊断意义. 当代医学, 2015, 21(36): 43-44.
19. Giovanella L, Clark PM, Chiovato L,et al. Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper. Eur J Endocrinol, 2014, 171(2): R33-R46.
20. Gurleyik E, Dogan S. Accuracy of unstimulated Basal serum thyroglobulin levels in assessing the completeness of thyroidectomy. J Clin Med Res, 2014, 6(5): 369-373.
21. Yang X, Liang J, Li T,et al. Preablative stimulated thyroglobulin correlates to new therapy response system in differentiated thyroid cancer. J Clin Endocrinol Metab, 2016, 101(3): 1307-1313.
22. 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. Clin Nucl Med, 2013, 38(1): 18-24.
23. Polachek A, Hirsch D, Tzvetov G,et al. Prognostic value of post-thyroidectomy thyroglobulin levels in patients with differentiated thyroid cancer. J Endocrinol Invest, 2011, 34(11): 855-860.
24. Piccardo A, Arecco F, Morbelli S,et al. Low thyroglobulin concentrations after thyroidectomy increase the prognostic value of undetectable thyroglobulin levels on levo-thyroxine suppressive treatment in low-risk differentiated thyroid cancer. J Endocrinol Invest, 2010, 33(2): 83-87.
25. Heemstra KA, Liu YY, Stokkel M,et al. Serum thyroglobulin concentrations predict disease-free remission and death in differentiated thyroid carcinoma. Clin Endocrinol (Oxf), 2007, 66(1): 58-64.
26. 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. Clin Nucl Med, 2012, 37(11): 1069-1074.
27. Krajewska J, Jarzab M, Czarniecka A,et al. Ongoing risk stratification for differentiated thyroid cancer (DTC)-stimulated serum thyroglobulin (Tg) before radioiodine (RAI) ablation, the most potent risk factor of cancer recurrence in M0 patients. Endokrynol Pol, 2016, 67(1): 2-11.
28. Phan HT, Jager PL, van der Wal JE,et al. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Eur J Endocrinol, 2008, 158(1): 77-83.
29. David A, Blotta A, Bondanelli M,et al. Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone. J Nucl Med, 2001, 42(10): 1470-1475.
30. Robenshtok E, Tuttle RM. Role of recombinant human thyrotropin (rhTSH) in the treatment of well-differentiated thyroid cancer. Indian J Surg Oncol, 2012, 3(3): 182-189.
31. Zhao T, Liang J, Guo Z,et al. Serum thyrotropin level of 30 μIU/mL is inadequate for preablative thyroglobulin to serve as a prognostic marker for differentiated thyroid cancer. Endocrine, 2016, 53(1): 166-173.
32. 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 Clin Endocrinol Metab, 2012, 97(8): 2754-2763.
33. Bertagna F, Albano D, Bosio G,et al.¹⁸F-FDG-PET/CT in patients affected by differentiated thyroid carcinoma with positive thyroglobulin level and negative¹³¹I whole body scan. It’s value confirmed by a bicentric experience. Curr Radiopharm, 2016, 9(36): 1022-1035.
34. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer; Cooper DS, Doherty GM,et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid, 2009, 19(11): 1167-1214.
35. Özdemir E, Yildirim Poyraz N, Polat SB,et al. Diagnostic value of¹⁸F-FDG PET/CT in patients with TENIS syndrome: correlation with thyroglobulin levels. Ann Nucl Med, 2014, 28(3): 241-247.

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