Role of calcitonin for diagnosis and treatment of medullary thyroid carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

RAN Yanhao , ZHENG Xun ,  WEI Tao

Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

WEI Tao, Email: surgeonwei@163.com

Keywords：

calcitonin; medullary thyroid cancer; diagnosis; treatment

DOI：

10.7507/1007-9424.202301022

Video：

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Objective To understand the role of calcitonin testing for the diagnosis and treatment of medullary thyroid cancer (MTC) as well as recent research progress, so as to provide assistance in the early clinical diagnosis and treatment of MTC and improve patients’ prognosis. Method The literatures about the role of calcitonin testing in MTC in recent years were reviewed. Results In recent years, both domestic and international scholars had extensively investigated the role of calcitonin in the early detection of MTC and accurate postoperative prognosis assessment. With respect to early diagnosis, advancements had been made in the three main measurement methods: basal calcitonin, stimulated calcitonin, and calcitonin measurement in the thyroid nodule fine-needle aspiration washout fluid. These developments in calcitonin levels had contributed to improved guidance in surgical treatment and prognosis evaluation. While calcitonin monitoring could inform treatment decisions and improve patients’prognosis, numerous challenges remain to be addressed. Conclusion The study of calcitonin detection can deepen the understanding of MTC, further research on calcitonin related detection in the future will be of great significance for the diagnosis, treatment and prognosis evaluation of MTC.

Citation： RAN Yanhao, ZHENG Xun, WEI Tao. Role of calcitonin for diagnosis and treatment of medullary thyroid carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(6): 751-756. doi: 10.7507/1007-9424.202301022 Copy

1.	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.
2.	Kebebew E, Ituarte PH, Siperstein AE, et al. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer, 2000, 88(5): 1139-1148.
3.	Jiménez C, Hu MI, Gagel RF. Management of medullary thyroid carcinoma. Endocrinol Metab Clin North Am, 2008, 37(2): 481-496.
4.	Pacini F, Castagna MG, Cipri C, et al. Medullary thyroid carcinoma. Clin Oncol (R Coll Radiol), 2010, 22(6): 475-485.
5.	Gharib H, Papini E, Paschke R, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. Endocr Pract, 2010, 16(3): 468-475.
6.	Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid, 2015, 25(6): 567-610.
7.	Costante G, Durante C, Francis Z, et al. Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat Clin Pract Endocrinol Metab, 2009, 5(1): 35-44.
8.	高明, 葛明华. 甲状腺肿瘤学. 北京: 人民卫生出版, 2018: 153-154.
9.	Schneider HG, Lam QT. Procalcitonin for the clinical laboratory: a review. Pathology, 2007, 39(4): 383-390.
10.	Novotny AR, Luppa P, Rosenberg R, et al. Procalcitonin can be used for monitoring sepsis in patients with medullary thyroid carcinoma. Thyroid, 2009, 19(11): 1287-1289.
11.	Meisner M, Tschaikowsky K, Schnabel S, et al. Procalcitonin—influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Eur J Clin Chem Clin Biochem, 1997, 35(8): 597-601.
12.	Meisner M, Schmidt J, Hüttner H, et al. The natural elimination rate of procalcitonin in patients with normal and impaired renal function. Intensive Care Med, 2000, 26 Suppl 2: S212-S216. doi: 10.1007/BF02900740.
13.	Giovanella L, Garo ML, Ceriani L, et al. Procalcitonin as an alternative tumor marker of medullary thyroid carcinoma. J Clin Endocrinol Metab, 2021, 106(12): 3634-3643.
14.	Cohen R, Campos JM, Salaün C, et al. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d’Etudes des Tumeurs a Calcitonine (GETC). J Clin Endocrinol Metab, 2000, 85(2): 919-922.
15.	Elisei R, Bottici V, Luchetti F, et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10 864 patients with nodular thyroid disorders. J Clin Endocrinol Metab, 2004, 89(1): 163-168.
16.	Verbeek HH, de Groot JWB, Sluiter WJ, et al. Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules. Cochrane Database Syst Rev, 2020, 3(3): CD010159. doi: 10.1002/14651858.CD010159.pub2.
17.	Jassal K, Ravintharan N, Prabhakaran S, et al. Preoperative serum calcitonin may improve initial surgery for medullary thyroid cancer in patients with indeterminate cytology. ANZ J Surg, 2022, 92(6): 1428-1433.
18.	Workman AD, Soylu S, Kamani D, et al. Limitations of preoperative cytology for medullary thyroid cancer: proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery. Head Neck, 2021, 43(3): 920-927.
19.	Thomas CM, Asa SL, Ezzat S, et al. Diagnosis and pathologic characteristics of medullary thyroid carcinoma—review of current guidelines. Curr Oncol, 2019, 26(5): 338-344.
20.	Niederle MB, Scheuba C, Riss P, et al. Early diagnosis of medullary thyroid cancer: are calcitonin stimulation tests still indicated in the era of highly sensitive calcitonin immunoassays? Thyroid, 2020, 30(7): 974-984.
21.	Vannucchi G, Covelli D, Vigo B, et al. Thyroid volume and serum calcitonin changes during pregnancy. J Endocrinol Invest, 2017, 40(7): 727-732.
22.	Băetu M, Olariu CA, Moldoveanu G, et al. Calcitonin stimulation tests: rationale, technical issues and side effects: a review. Horm Metab Res, 2021, 53(6): 355-363.
23.	Doyle P, Düren C, Nerlich K, et al. Potency and tolerance of calcitonin stimulation with high-dose calcium versus pentagastrin in normal adults. J Clin Endocrinol Metab, 2009, 94(8): 2970-2974.
24.	Niederle MB, Scheuba C, Gessl A, et al. Calcium-stimulated calcitonin—The “new standard” in the diagnosis of thyroid C-cell disease —clinically relevant gender-specific cut-off levels for an “old test”. Biochem Med (Zagreb), 2018, 28(3): 030710.
25.	Pina G, Dubois S, Murat A, et al. Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test? Clin Endocrinol (Oxf), 2013, 78(3): 358-364.
26.	Vardarli I, Weber M, Weidemann F, et al. Diagnostic accuracy of routine calcitonin measurement for the detection of medullary thyroid carcinoma in the management of patients with nodular thyroid disease: a meta-analysis. Endocr Connect, 2021, 10(3): 358-370.
27.	Fugazzola L, Di Stefano M, Censi S, et al. Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment. J Endocrinol Invest, 2021, 44(3): 587-597.
28.	Trimboli P, Guidobaldi L, Crescenzi A, et al. The essential use of FNA-calcitonin for detecting medullary thyroid cancer. Endocrine, 2014, 47(1): 342-344.
29.	Boi F, Maurelli I, Pinna G, et al. Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab, 2007, 92(6): 2115-2118.
30.	Trimboli P, Cremonini N, Ceriani L, et al. Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study. Clin Endocrinol (Oxf), 2014, 80(1): 135-140.
31.	Trimboli P, Giannelli J, Marques B, et al. Head-to-head comparison of FNA cytology vs. calcitonin measurement in FNA washout fluids (FNA-CT) to diagnose medullary thyroid carcinoma. A systematic review and meta-analysis. Endocrine, 2022, 75(1): 33-39.
32.	Wang M, Chen H, Wang Y, et al. Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma. Clin Endocrinol (Oxf), 2023, 98(5): 709-718.
33.	Marques B, Cunha N, Martins RG, et al. Lymph node metastases of medullary thyroid cancer: role of calcitonin in the washout fluid of fine-needle aspiration. Int J Endocrinol, 2020, 2020: 9267972. doi: 10.1155/2020/9267972.
34.	Gökçay Canpolat A, Şahin M, Ceyhan K, et al. Calcitonin levels in washout samples vs. cytology in the detection of malignant lymph node metastasis in recurrent medullary thyroid cancer . Turk J Med Sci, 2021, 51(6): 3061-3066.
35.	Trimboli P, Guidobaldi L, Bongiovanni M, et al. Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: a systematic review. Diagn Cytopathol, 2016, 44(1): 45-51.
36.	Brutsaert EF, Gersten AJ, Tassler AB, et al. Medullary thyroid cancer with undetectable serum calcitonin. J Clin Endocrinol Metab, 2015, 100(2): 337-341.
37.	Zhang G, Jiang Y, Zhang S, et al. Genetic analysis of a hereditary medullary thyroid carcinoma case with normal preoperative serum calcitonin levels. Pathol Res Pract, 2019, 215(10): 152529. doi: 10.1016/j.prp.2019.152529.
38.	Wang TS, Ocal IT, Sosa JA, et al. Medullary thyroid carcinoma without marked elevation of calcitonin: a diagnostic and surveillance dilemma. Thyroid, 2008, 18(8): 889-894.
39.	Busnardo B, Girelli ME, Simioni N, et al. Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer, 1984, 53(2): 278-285.
40.	Inzerillo AM, Zaidi M, Huang CL. Calcitonin: the other thyroid hormone. Thyroid, 2002, 12(9): 791-798.
41.	Essig GF, Porter K, Schneider D, et al. Multifocality in sporadic medullary thyroid carcinoma: an international multicenter study. Thyroid, 2016, 26(11): 1563-1572.
42.	Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab, 2010, 95(6): 2655-2663.
43.	Spanheimer PM, Ganly I, Chou JF, et al. Prophylactic lateral neck dissection for medullary thyroid carcinoma is not associated with improved survival. Ann Surg Oncol, 2021, 28(11): 6572-6579.
44.	Randle RW, Balentine CJ, Leverson GE, et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery, 2017, 161(1): 137-146.
45.	Tuttle RM, Ganly I. Risk stratification in medullary thyroid cancer: moving beyond static anatomic staging. Oral Oncol, 2013, 49(7): 695-701.
46.	Bihan H, Becker KL, Snider RH, et al. Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid, 2003, 13(8): 819-822.
47.	Machens A, Lorenz K, Dralle H. Prediction of biochemical cure in pati-ents with medullary thyroid cancer. Br J Surg, 2020, 107(6): 695-704.
48.	Machens A, Lorenz K, Dralle H. Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer. Br J Surg, 2019, 106(4): 412-418.
49.	Miyauchi A, Onishi T, Morimoto S, et al. Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann Surg, 1984, 199(4): 461-466.
50.	Barbet J, Campion L, Kraeber-Bodéré F, et al. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab, 2005, 90(11): 6077-6084.
51.	Ito Y, Miyauchi A, Kihara M, et al. Calcitonin doubling time in medullary thyroid carcinoma after the detection of distant metastases keenly predicts patients’ carcinoma death. Endocr J, 2016, 63(7): 663-667.

1. 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.
2. Kebebew E, Ituarte PH, Siperstein AE, et al. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer, 2000, 88(5): 1139-1148.
3. Jiménez C, Hu MI, Gagel RF. Management of medullary thyroid carcinoma. Endocrinol Metab Clin North Am, 2008, 37(2): 481-496.
4. Pacini F, Castagna MG, Cipri C, et al. Medullary thyroid carcinoma. Clin Oncol (R Coll Radiol), 2010, 22(6): 475-485.
5. Gharib H, Papini E, Paschke R, et al. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules: executive summary of recommendations. Endocr Pract, 2010, 16(3): 468-475.
6. Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid, 2015, 25(6): 567-610.
7. Costante G, Durante C, Francis Z, et al. Determination of calcitonin levels in C-cell disease: clinical interest and potential pitfalls. Nat Clin Pract Endocrinol Metab, 2009, 5(1): 35-44.
8. 高明, 葛明华. 甲状腺肿瘤学. 北京: 人民卫生出版, 2018: 153-154.
9. Schneider HG, Lam QT. Procalcitonin for the clinical laboratory: a review. Pathology, 2007, 39(4): 383-390.
10. Novotny AR, Luppa P, Rosenberg R, et al. Procalcitonin can be used for monitoring sepsis in patients with medullary thyroid carcinoma. Thyroid, 2009, 19(11): 1287-1289.
11. Meisner M, Tschaikowsky K, Schnabel S, et al. Procalcitonin—influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations. Eur J Clin Chem Clin Biochem, 1997, 35(8): 597-601.
12. Meisner M, Schmidt J, Hüttner H, et al. The natural elimination rate of procalcitonin in patients with normal and impaired renal function. Intensive Care Med, 2000, 26 Suppl 2: S212-S216. doi: 10.1007/BF02900740.
13. Giovanella L, Garo ML, Ceriani L, et al. Procalcitonin as an alternative tumor marker of medullary thyroid carcinoma. J Clin Endocrinol Metab, 2021, 106(12): 3634-3643.
14. Cohen R, Campos JM, Salaün C, et al. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d’Etudes des Tumeurs a Calcitonine (GETC). J Clin Endocrinol Metab, 2000, 85(2): 919-922.
15. Elisei R, Bottici V, Luchetti F, et al. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10 864 patients with nodular thyroid disorders. J Clin Endocrinol Metab, 2004, 89(1): 163-168.
16. Verbeek HH, de Groot JWB, Sluiter WJ, et al. Calcitonin testing for detection of medullary thyroid cancer in people with thyroid nodules. Cochrane Database Syst Rev, 2020, 3(3): CD010159. doi: 10.1002/14651858.CD010159.pub2.
17. Jassal K, Ravintharan N, Prabhakaran S, et al. Preoperative serum calcitonin may improve initial surgery for medullary thyroid cancer in patients with indeterminate cytology. ANZ J Surg, 2022, 92(6): 1428-1433.
18. Workman AD, Soylu S, Kamani D, et al. Limitations of preoperative cytology for medullary thyroid cancer: proposal for improved preoperative diagnosis for optimal initial medullary thyroid carcinoma specific surgery. Head Neck, 2021, 43(3): 920-927.
19. Thomas CM, Asa SL, Ezzat S, et al. Diagnosis and pathologic characteristics of medullary thyroid carcinoma—review of current guidelines. Curr Oncol, 2019, 26(5): 338-344.
20. Niederle MB, Scheuba C, Riss P, et al. Early diagnosis of medullary thyroid cancer: are calcitonin stimulation tests still indicated in the era of highly sensitive calcitonin immunoassays? Thyroid, 2020, 30(7): 974-984.
21. Vannucchi G, Covelli D, Vigo B, et al. Thyroid volume and serum calcitonin changes during pregnancy. J Endocrinol Invest, 2017, 40(7): 727-732.
22. Băetu M, Olariu CA, Moldoveanu G, et al. Calcitonin stimulation tests: rationale, technical issues and side effects: a review. Horm Metab Res, 2021, 53(6): 355-363.
23. Doyle P, Düren C, Nerlich K, et al. Potency and tolerance of calcitonin stimulation with high-dose calcium versus pentagastrin in normal adults. J Clin Endocrinol Metab, 2009, 94(8): 2970-2974.
24. Niederle MB, Scheuba C, Gessl A, et al. Calcium-stimulated calcitonin—The “new standard” in the diagnosis of thyroid C-cell disease —clinically relevant gender-specific cut-off levels for an “old test”. Biochem Med (Zagreb), 2018, 28(3): 030710.
25. Pina G, Dubois S, Murat A, et al. Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test? Clin Endocrinol (Oxf), 2013, 78(3): 358-364.
26. Vardarli I, Weber M, Weidemann F, et al. Diagnostic accuracy of routine calcitonin measurement for the detection of medullary thyroid carcinoma in the management of patients with nodular thyroid disease: a meta-analysis. Endocr Connect, 2021, 10(3): 358-370.
27. Fugazzola L, Di Stefano M, Censi S, et al. Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment. J Endocrinol Invest, 2021, 44(3): 587-597.
28. Trimboli P, Guidobaldi L, Crescenzi A, et al. The essential use of FNA-calcitonin for detecting medullary thyroid cancer. Endocrine, 2014, 47(1): 342-344.
29. Boi F, Maurelli I, Pinna G, et al. Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab, 2007, 92(6): 2115-2118.
30. Trimboli P, Cremonini N, Ceriani L, et al. Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study. Clin Endocrinol (Oxf), 2014, 80(1): 135-140.
31. Trimboli P, Giannelli J, Marques B, et al. Head-to-head comparison of FNA cytology vs. calcitonin measurement in FNA washout fluids (FNA-CT) to diagnose medullary thyroid carcinoma. A systematic review and meta-analysis. Endocrine, 2022, 75(1): 33-39.
32. Wang M, Chen H, Wang Y, et al. Diagnostic value and cost-effectiveness of FNA-CT versus FNAC for medullary thyroid carcinoma. Clin Endocrinol (Oxf), 2023, 98(5): 709-718.
33. Marques B, Cunha N, Martins RG, et al. Lymph node metastases of medullary thyroid cancer: role of calcitonin in the washout fluid of fine-needle aspiration. Int J Endocrinol, 2020, 2020: 9267972. doi: 10.1155/2020/9267972.
34. Gökçay Canpolat A, Şahin M, Ceyhan K, et al. Calcitonin levels in washout samples vs. cytology in the detection of malignant lymph node metastasis in recurrent medullary thyroid cancer . Turk J Med Sci, 2021, 51(6): 3061-3066.
35. Trimboli P, Guidobaldi L, Bongiovanni M, et al. Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: a systematic review. Diagn Cytopathol, 2016, 44(1): 45-51.
36. Brutsaert EF, Gersten AJ, Tassler AB, et al. Medullary thyroid cancer with undetectable serum calcitonin. J Clin Endocrinol Metab, 2015, 100(2): 337-341.
37. Zhang G, Jiang Y, Zhang S, et al. Genetic analysis of a hereditary medullary thyroid carcinoma case with normal preoperative serum calcitonin levels. Pathol Res Pract, 2019, 215(10): 152529. doi: 10.1016/j.prp.2019.152529.
38. Wang TS, Ocal IT, Sosa JA, et al. Medullary thyroid carcinoma without marked elevation of calcitonin: a diagnostic and surveillance dilemma. Thyroid, 2008, 18(8): 889-894.
39. Busnardo B, Girelli ME, Simioni N, et al. Nonparallel patterns of calcitonin and carcinoembryonic antigen levels in the follow-up of medullary thyroid carcinoma. Cancer, 1984, 53(2): 278-285.
40. Inzerillo AM, Zaidi M, Huang CL. Calcitonin: the other thyroid hormone. Thyroid, 2002, 12(9): 791-798.
41. Essig GF, Porter K, Schneider D, et al. Multifocality in sporadic medullary thyroid carcinoma: an international multicenter study. Thyroid, 2016, 26(11): 1563-1572.
42. Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab, 2010, 95(6): 2655-2663.
43. Spanheimer PM, Ganly I, Chou JF, et al. Prophylactic lateral neck dissection for medullary thyroid carcinoma is not associated with improved survival. Ann Surg Oncol, 2021, 28(11): 6572-6579.
44. Randle RW, Balentine CJ, Leverson GE, et al. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery, 2017, 161(1): 137-146.
45. Tuttle RM, Ganly I. Risk stratification in medullary thyroid cancer: moving beyond static anatomic staging. Oral Oncol, 2013, 49(7): 695-701.
46. Bihan H, Becker KL, Snider RH, et al. Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid, 2003, 13(8): 819-822.
47. Machens A, Lorenz K, Dralle H. Prediction of biochemical cure in pati-ents with medullary thyroid cancer. Br J Surg, 2020, 107(6): 695-704.
48. Machens A, Lorenz K, Dralle H. Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer. Br J Surg, 2019, 106(4): 412-418.
49. Miyauchi A, Onishi T, Morimoto S, et al. Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma. Ann Surg, 1984, 199(4): 461-466.
50. Barbet J, Campion L, Kraeber-Bodéré F, et al. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab, 2005, 90(11): 6077-6084.
51. Ito Y, Miyauchi A, Kihara M, et al. Calcitonin doubling time in medullary thyroid carcinoma after the detection of distant metastases keenly predicts patients’ carcinoma death. Endocr J, 2016, 63(7): 663-667.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Role of calcitonin for diagnosis and treatment of medullary thyroid carcinoma

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