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Medullary Thyroid Carcinoma (MTC): Diagnosis, Treatment and Follow-Up

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Atlas of Thyroid and Neuroendocrine Tumor Markers

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Abstract

Medullary thyroid carcinoma (MTC) is a rare thyroid tumour (2–5% of all thyroid malignancies) deriving from thyroid C-cells. Calcitonin is the main secretory product and marker for diagnosis and follow-up. MTC frequently metastasizes to cervical lymph nodes and may give distant metastases. This tumour is familial in 25% of cases, frequently in the context of multiple endocrine neoplasia syndromes. Mutations in the RET proto-oncogene are responsible for transmission of the inherited disease. The majority of mutations responsible for familial disease have now been recognized, and the molecular study is routinely performed in all MTC cases. Gene carriers can be thus identified at a preclinical stage, and prophylactic thyroidectomy may be performed. The risk level associated with the various mutations has now been studied and appears to be variable. The most important treatment is surgery. The treatment strategies for recurrent and metastatic disease remain a challenge. Tyrosine kinase inhibitors are the therapeutic agents currently used in patients with advanced, metastatic or rapidly progressive disease and result in stabilization of the disease in the majority of patients, especially those carrying a RET mutation.

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References

  1. Elisei R, Bottici V, Luchetti F, Di Coscio G, Romei C, Grasso L, Miccoli P, Iacconi P, Basolo F, Pinchera A, Pacini F. 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):163–8.

    Article  CAS  PubMed  Google Scholar 

  2. Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. https://doi.org/10.1089/thy.2014.0335.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Trimboli P, Seregni E, Treglia G, Alevizaki M, Giovanella L. Procalcitonin for detecting medullary thyroid carcinoma: a systematic review. Endocr Relat Cancer. 2015;22(3):R157–64. https://doi.org/10.1530/erc-15-0156.

    Article  CAS  PubMed  Google Scholar 

  4. Kebebew E, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 2000;88(5):1139–48. https://doi.org/10.1002/(SICI)1097-0142(20000301)88:5<1139::AID-CNCR26>3.0.CO;2-Z. [pii]

    Article  CAS  PubMed  Google Scholar 

  5. Modigliani E, Cohen R, Campos JM, Conte-Devolx B, Maes B, Boneu A, Schlumberger M, Bigorgne JC, Dumontier P, Leclerc L, Corcuff B, Guilhem I. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d'etude des tumeurs a calcitonine. Clin Endocrinol. 1998;48(3):265–73.

    Article  CAS  Google Scholar 

  6. Alevizaki M, Saltiki K, Rentziou G, Papathoma A, Sarika L, Vasileiou V, Anastasiou E. Medullary thyroid carcinoma: the influence of policy changing in clinical characteristics and disease progression. Eur J Endocrinol. 2012;167(6):799–808. https://doi.org/10.1530/EJE-12-0388. [pii] EJE-12-0388

    Article  CAS  PubMed  Google Scholar 

  7. Verbeek HH, Meijer JA, Zandee WT, Kramp KH, Sluiter WJ, Smit JW, Kievit J, Links TP, Plukker JT. Fewer cancer reoperations for medullary thyroid cancer after initial surgery according to ATA guidelines. Ann Surg Oncol. 2015;22(4):1207–13. https://doi.org/10.1245/s10434-014-4115-6.

    Article  PubMed  Google Scholar 

  8. Saltiki K, Rentziou G, Stamatelopoulos K, Georgiopoulos G, Stavrianos C, Lambrinoudaki E, Alevizaki M. Small medullary thyroid carcinoma: post-operative calcitonin rather than tumour size predicts disease persistence and progression. Eur J Endocrinol. 2014;171(1):117–26. https://doi.org/10.1530/eje-14-0076.

    Article  CAS  PubMed  Google Scholar 

  9. Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer. 2006;107(9):2134–42. https://doi.org/10.1002/cncr.22244.

    Article  PubMed  Google Scholar 

  10. Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, Skinner M, Krebs A, Vasselli J, Schlumberger M. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol. 2010;28(5):767–72. https://doi.org/10.1200/JCO.2009.23.6604. [pii] JCO.2009.23.6604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Elisei R, Schlumberger MJ, Muller SP, Schoffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013;31(29):3639–46. https://doi.org/10.1200/jco.2012.48.4659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ahmed SR, Ball DW. Clinical review: Incidentally discovered medullary thyroid cancer: diagnostic strategies and treatment. J Clin Endocrinol Metab. 2011;96(5):1237–45. https://doi.org/10.1210/jc.2010-2359. [pii] jc.2010-2359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Valle LA, Kloos RT. The prevalence of occult medullary thyroid carcinoma at autopsy. J Clin Endocrinol Metab. 2011;96(1):E109–13. https://doi.org/10.1210/jc.2010-0959. [pii] jc.2010-0959

    Article  CAS  PubMed  Google Scholar 

  14. Trimboli P, Cremonini N, Ceriani L, Saggiorato E, Guidobaldi L, Romanelli F, Ventura C, Laurenti O, Messuti I, Solaroli E, Madaio R, Bongiovanni M, Orlandi F, Crescenzi A, Valabrega S, Giovanella L. Calcitonin measurement in aspiration needle washout fluids has higher sensitivity than cytology in detecting medullary thyroid cancer: a retrospective multicentre study. Clin Endocrinol. 2014;80(1):135–40. https://doi.org/10.1111/cen.12234.

    Article  CAS  Google Scholar 

  15. Boi F, Maurelli I, Pinna G, Atzeni F, Piga M, Lai ML, Mariotti S. 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):2115–8. https://doi.org/10.1210/jc.2007-0326. [pii] jc.2007-0326

    Article  CAS  PubMed  Google Scholar 

  16. Trimboli P, Guidobaldi L, Bongiovanni M, Crescenzi A, Alevizaki M, Giovanella L. Use of fine-needle aspirate calcitonin to detect medullary thyroid carcinoma: a systematic review. Diagn Cytopathol. 2016;44(1):45–51. https://doi.org/10.1002/dc.23375.

    Article  PubMed  Google Scholar 

  17. Scollo C, Baudin E, Travagli JP, Caillou B, Bellon N, Leboulleux S, Schlumberger M. Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab. 2003;88(5):2070–5.

    Article  CAS  PubMed  Google Scholar 

  18. Alevizaki M, Saltiki K. Primary hyperparathyroidism in MEN2 syndromes. Recent Results Cancer Res. 2015;204:179–86. https://doi.org/10.1007/978-3-319-22542-5_8.

    Article  PubMed  Google Scholar 

  19. Machens A, Dralle H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab. 2010;95(6):2655–63. https://doi.org/10.1210/jc.2009-2368. [pii] jc.2009-2368

    Article  CAS  PubMed  Google Scholar 

  20. Cohen R, Campos JM, Salaun C, Heshmati HM, Kraimps JL, Proye C, Sarfati E, Henry JF, Niccoli-Sire P, Modigliani E. 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):919–22.

    Article  CAS  PubMed  Google Scholar 

  21. Trimboli P, Giovanella L. Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature. Clin Chem Lab Med. 2015;53(10):1507–14. https://doi.org/10.1515/cclm-2015-0058.

    Article  CAS  PubMed  Google Scholar 

  22. Karagiannis AK, Girio-Fragkoulakis C, Nakouti T. Procalcitonin: a new biomarker for medullary thyroid cancer? A systematic review. Anticancer Res. 2016;36(8):3803–10.

    CAS  PubMed  Google Scholar 

  23. Giovanella L, Crippa S, Cariani L. Serum calcitonin-negative medullary thyroid carcinoma: role of CgA and CEA as complementary markers. Int J Biol Markers. 2008;23(2):129–31.

    Article  CAS  PubMed  Google Scholar 

  24. Elisei R, Alevizaki M, Conte-Devolx B, Frank-Raue K, Leite V, Williams GR. 2012 European thyroid association guidelines for genetic testing and its clinical consequences in medullary thyroid cancer. Eur Thyroid J. 2013;1(4):216–31. https://doi.org/10.1159/000346174.

    Article  CAS  PubMed  Google Scholar 

  25. Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612. https://doi.org/10.1089/thy.2008.0403.

    Article  PubMed  Google Scholar 

  26. Preissner CM, Dodge LA, O'Kane DJ, Singh RJ, Grebe SK. Prevalence of heterophilic antibody interference in eight automated tumor marker immunoassays. Clin Chem. 2005;51(1):208–10. https://doi.org/10.1373/clinchem.2004.040501.

    Article  CAS  PubMed  Google Scholar 

  27. Kwon H, Kim WG, Choi YM, Jang EK, Jeon MJ, Song DE, Baek JH, Ryu JS, Hong SJ, Kim TY, Kim WB, Shong YK. A cut-off value of basal serum calcitonin for detecting macroscopic medullary thyroid carcinoma. Clin Endocrinol. 2015;82(4):598–603. https://doi.org/10.1111/cen.12562.

    Article  CAS  Google Scholar 

  28. Mian C, Perrino M, Colombo C, Cavedon E, Pennelli G, Ferrero S, De Leo S, Sarais C, Cacciatore C, Manfredi GI, Verga U, Iacobone M, De Pasquale L, Pelizzo MR, Vicentini L, Persani L, Fugazzola L. Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety. J Clin Endocrinol Metab. 2014;99(5):1656–64. https://doi.org/10.1210/jc.2013-4088.

    Article  CAS  PubMed  Google Scholar 

  29. Fugazzola L. Stimulated calcitonin cut-offs by different tests. Eur Thyroid J. 2013;2(1):49–56. https://doi.org/10.1159/000346020.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Machens A, Hoffmann F, Sekulla C, Dralle H. Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer. Endocr Relat Cancer. 2009;16(4):1291–8. https://doi.org/10.1677/ERC-09-0136. [pii] ERC-09-0136

    Article  CAS  PubMed  Google Scholar 

  31. Cho YY, Jang HW, Jang JY, Kim TH, Choe JH, Kim JH, Kim JS, Kim SW, Chung JH. Clinical outcomes of patients with hypercalcitoninemia after initial treatment for medullary thyroid cancer and postoperative serum calcitonin cutoffs for predicting structural recurrence. Head Neck. 2016;38(10):1501–8. https://doi.org/10.1002/hed.24469.

    Article  PubMed  Google Scholar 

  32. Siironen P, Hagstrom J, Maenpaa HO, Louhimo J, Arola J, Haglund C. Lymph node metastases and elevated postoperative calcitonin: predictors of poor survival in medullary thyroid carcinoma. Acta Oncol. 2016;55(3):357–64. https://doi.org/10.3109/0284186x.2015.1070963.

    Article  CAS  PubMed  Google Scholar 

  33. Mendelsohn G, Wells SA Jr, Baylin SB. Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. An immunohistochemical study in early, localized, and virulent disseminated stages of disease. Cancer. 1984;54(4):657–62.

    Article  CAS  PubMed  Google Scholar 

  34. Lim SK, Guechot J, Vaubourdolle M. Negative predictive value of procalcitonin in medullary thyroid carcinoma. Ann Biol Clin (Paris). 2016;74(2):213–8. https://doi.org/10.1684/abc.2015.1115.

    Google Scholar 

  35. Walter MA, Meier C, Radimerski T, Iten F, Kranzlin M, Muller-Brand J, de Groot JW, Kema IP, Links TP, Muller B. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer. 2010;116(1):31–40. https://doi.org/10.1002/cncr.24738.

    CAS  PubMed  Google Scholar 

  36. Alevizaki M, Grigorakis SI, Tseleni-Balafouta S, Alevizaki CC, Philippou G, Anastasiou E, Souvatzoglou A. High plasma amylin/islet amyloid polypeptide levels in patients with residual medullary thyroid carcinoma after total thyroidectomy. Eur J Endocrinol. 2001;145(5):585–9.

    Article  CAS  PubMed  Google Scholar 

  37. Wimalawansa SJ. CGRP radioreceptor assay: a new diagnostic tool for medullary thyroid carcinoma. J Bone Miner Res. 1993;8(4):467–73. https://doi.org/10.1002/jbmr.5650080411.

    Article  CAS  PubMed  Google Scholar 

  38. Raue F, Blind E, Grauer A. PDN-21 (katacalcin) and chromogranin A: tumor markers for medullary thyroid carcinoma. Henry Ford Hosp Med J. 1992;40(3–4):296–8.

    CAS  PubMed  Google Scholar 

  39. Blind E, Raue F, Klaiber T, Zink A, Schroth J, Buhr H, Ziegler R. Evaluation of sensitive PDN-21 (katacalcin) determination as tumor marker in medullary thyroid carcinoma. J Endocrinol Investig. 1992;15(2):93–8.

    Article  CAS  Google Scholar 

  40. Barbet J, Campion L, Kraeber-Bodere F, Chatal JF. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2005;90(11):6077–84. https://doi.org/10.1210/jc.2005-0044. [pii] jc.2005-0044

    Article  CAS  PubMed  Google Scholar 

  41. van Veelen W, de Groot JW, Acton DS, Hofstra RM, Hoppener JW, Links TP, Lips CJ. Medullary thyroid carcinoma and biomarkers: past, present and future. J Intern Med. 2009;266(1):126–40. https://doi.org/10.1111/j.1365-2796.2009.02106.x. [pii] JIM2106

    Article  PubMed  Google Scholar 

  42. Machens A, Ukkat J, Hauptmann S, Dralle H. Abnormal carcinoembryonic antigen levels and medullary thyroid cancer progression: a multivariate analysis. Arch Surg. 2007;142(3):289–293.; discussion 294. https://doi.org/10.1001/archsurg.142.3.289.

    Article  CAS  PubMed  Google Scholar 

  43. Milman S, Arnold JL, Price M, Negassa A, Surks MI, Fleischer N, Whitney KD. Medullary thyroid cancer that stains negative for ca 19-9 has decreased metastatic potential. Endocr Pract. 2015;21(6):590–4. https://doi.org/10.4158/ep14357.or.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Elisei R, Lorusso L, Piaggi P, Torregrossa L, Pellegrini G, Molinaro E, Agate L, Bottici V, Pani F, Cacciato Insilla A, Casella F, Ciampi R, Tognetti I, Materazzi G, Basolo F, Romei C. Elevated level of serum carbohydrate antigen 19.9 as predictor of mortality in patients with advanced medullary thyroid cancer. Eur J Endocrinol. 2015;173(3):297–304. https://doi.org/10.1530/eje-15-0304.

    Article  CAS  PubMed  Google Scholar 

  45. de Groot JW, Kema IP, Breukelman H, van der Veer E, Wiggers T, Plukker JT, Wolffenbuttel BH, Links TP. Biochemical markers in the follow-up of medullary thyroid cancer. Thyroid. 2006;16(11):1163–70. https://doi.org/10.1089/thy.2006.16.1163.

    Article  PubMed  Google Scholar 

  46. Barakat MT, Meeran K, Bloom SR. Neuroendocrine tumours. Endocr Relat Cancer. 2004;11(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  47. Pacini F, Elisei R, Anelli S, Gasperini L, Schipani E, Pinchera A. Circulating neuron-specific enolase in medullary thyroid cancer. Int J Biol Markers. 1986;1(2):85–8.

    CAS  PubMed  Google Scholar 

  48. Moers AM, Landsvater RM, Schaap C, Jansen-Schillhorn van Veen JM, de Valk IA, Blijham GH, Hoppener JW, Vroom TM, van Amstel HK, Lips CJ. Familial medullary thyroid carcinoma: not a distinct entity? Genotype-phenotype correlation in a large family. Am J Med. 1996;101(6):635–41.

    Article  CAS  PubMed  Google Scholar 

  49. Santoro M, Carlomagno F, Romano A, Bottaro DP, Dathan NA, Grieco M, Fusco A, Vecchio G, Matoskova B, Kraus MH, et al. Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science. 1995;267(5196):381–3.

    Article  CAS  PubMed  Google Scholar 

  50. Romei C, Mariotti S, Fugazzola L, Taccaliti A, Pacini F, Opocher G, Mian C, Castellano M, Degli Uberti E, Ceccherini I, Cremonini N, Seregni E, Orlandi F, Ferolla P, Puxeddu E, Giorgino F, Colao A, Loli P, Bondi F, Cosci B, Bottici V, Cappai A, Pinna G, Persani L, Verga U, Boscaro M, Castagna MG, Cappelli C, Zatelli MC, Faggiano A, Francia G, Brandi ML, Falchetti A, Pinchera A, Elisei R. Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes. Eur J Endocrinol. 2010;163(2):301–8. https://doi.org/10.1530/eje-10-0333.

    Article  CAS  PubMed  Google Scholar 

  51. Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, Agate L, Vivaldi A, Faviana P, Basolo F, Miccoli P, Berti P, Pacini F, Pinchera A. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93(3):682–7. https://doi.org/10.1210/jc.2007-1714. [pii] jc.2007-1714

    Article  CAS  PubMed  Google Scholar 

  52. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, van Amstel HK, Lips CJ, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xue F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjold M, Komminoth P, Hendy GN, Mulligan LM, et al. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA. 1996;276(19):1575–9.

    Article  CAS  PubMed  Google Scholar 

  53. Machens A, Gimm O, Hinze R, Hoppner W, Boehm BO, Dralle H. Genotype-phenotype correlations in hereditary medullary thyroid carcinoma: oncological features and biochemical properties. J Clin Endocrinol Metab. 2001;86(3):1104–9.

    CAS  PubMed  Google Scholar 

  54. Pappa T, Alevizaki M. Management of hereditary medullary thyroid carcinoma. Endocrine. 2016;53(1):7–17. https://doi.org/10.1007/s12020-016-0873-1.

    Article  CAS  PubMed  Google Scholar 

  55. Mathiesen JS, Kroustrup JP, Vestergaard P, Stochholm K, Poulsen PL, Rasmussen AK, Feldt-Rasmussen U, Gaustadnes M, Orntoft TF, van Overeem HT, Nielsen FC, Brixen K, Godballe C, Frederiksen AL. Distribution of RET mutations in multiple endocrine neoplasia 2 in Denmark 1994-2014: a nationwide study. Thyroid. 2017;27(2):215–23. https://doi.org/10.1089/thy.2016.0411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Raue F, Frank-Raue K. Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management. Hormones (Athens). 2009;8(1):23–8.

    Article  Google Scholar 

  57. Spinelli C, Di Giacomo M, Costanzo S, Elisei R, Miccoli P. Role of RET codonic mutations in the surgical management of medullary thyroid carcinoma in pediatric age multiple endocrine neoplasm type 2 syndromes. J Pediatr Surg. 2010;45(8):1610–6. https://doi.org/10.1016/j.jpedsurg.2010.03.019.

    Article  PubMed  Google Scholar 

  58. Machens A, Niccoli-Sire P, Hoegel J, Frank-Raue K, van Vroonhoven TJ, Roeher HD, Wahl RA, Lamesch P, Raue F, Conte-Devolx B, Dralle H. Early malignant progression of hereditary medullary thyroid cancer. N Engl J Med. 2003;349(16):1517–25. https://doi.org/10.1056/NEJMoa012915.

    Article  CAS  PubMed  Google Scholar 

  59. Skinner MA, Moley JA, Dilley WG, Owzar K, Debenedetti MK, Wells SA Jr. Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A. N Engl J Med. 2005;353(11):1105–13. https://doi.org/10.1056/NEJMoa043999.

    Article  CAS  PubMed  Google Scholar 

  60. Shepet K, Alhefdhi A, Lai N, Mazeh H, Sippel R, Chen H. Hereditary medullary thyroid cancer: age-appropriate thyroidectomy improves disease-free survival. Ann Surg Oncol. 2013;20(5):1451–5. https://doi.org/10.1245/s10434-012-2757-9.

    Article  PubMed  Google Scholar 

  61. Elisei R, Romei C, Renzini G, Bottici V, Cosci B, Molinaro E, Agate L, Cappagli V, Miccoli P, Berti P, Faviana P, Ugolini C, Basolo F, Vitti P, Pinchera A. The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. J Clin Endocrinol Metab. 2012;97(2):426–35. https://doi.org/10.1210/jc.2011-2046.

    Article  CAS  PubMed  Google Scholar 

  62. Romei C, Cosci B, Renzini G, Bottici V, Molinaro E, Agate L, Passannanti P, Viola D, Biagini A, Basolo F, Ugolini C, Materazzi G, Pinchera A, Vitti P, Elisei R. RET genetic screening of sporadic medullary thyroid cancer (MTC) allows the preclinical diagnosis of unsuspected gene carriers and the identification of a relevant percentage of hidden familial MTC (FMTC). Clin Endocrinol. 2011;74(2):241–7. https://doi.org/10.1111/j.1365-2265.2010.03900.x.

    Article  CAS  Google Scholar 

  63. Sarika HL, Papathoma A, Garofalaki M, Vasileiou V, Vlassopoulou B, Anastasiou E, Alevizaki M. High prevalence of exon 8 g533c mutation in apparently sporadic medullary thyroid carcinoma (mtc) in Greece. Clin Endocrinol. 2012;77(6):857–62. https://doi.org/10.1111/j.1365-2265.2012.04462.x.

    Article  CAS  Google Scholar 

  64. Sarika L, Papathoma A, Garofalaki M, Saltiki K, Pappa T, Pazaitou-Panayiotou K, Anastasiou E, Alevizaki M. Genetic screening of patients with Medullary Thyroid Cancer (MTC) in a referral center in Greece during the past two decades. Eur J Endocrinol. 2015;172(4):501–9. https://doi.org/10.1530/eje-14-0817.

    Article  CAS  PubMed  Google Scholar 

  65. Machens A, Frank-Raue K, Lorenz K, Rondot S, Raue F, Dralle H. Clinical relevance of RET variants G691S, L769L, S836S and S904S to sporadic medullary thyroid cancer. Clin Endocrinol. 2012;76(5):691–7. https://doi.org/10.1111/j.1365-2265.2011.04293.x.

    Article  CAS  Google Scholar 

  66. Miyauchi A, Matsuzuka F, Hirai K, Yokozawa T, Kobayashi K, Ito Y, Nakano K, Kuma K, Futami H, Yamaguchi K. Prospective trial of unilateral surgery for nonhereditary medullary thyroid carcinoma in patients without germline RET mutations. World J Surg. 2002;26(8):1023–8. https://doi.org/10.1007/s00268-002-6665-1.

    Article  PubMed  Google Scholar 

  67. Kebebew E, Greenspan FS, Clark OH, Woeber KA, Grunwell J. Extent of disease and practice patterns for medullary thyroid cancer. J Am Coll Surg. 2005;200(6):890–6. https://doi.org/10.1016/j.jamcollsurg.2004.12.011. [pii] S1072-7515(04)01544-3

    Article  PubMed  Google Scholar 

  68. Yip DT, Hassan M, Pazaitou-Panayiotou K, Ruan DT, Gawande AA, Gaz RD, Moore FD Jr, Hodin RA, Stephen AE, Sadow PM, Daniels GH, Randolph GW, Parangi S, Lubitz CC. Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma. Surgery. 2011;150(6):1168–77. https://doi.org/10.1016/j.surg.2011.09.043. [pii] S0039-6060(11)00557-5

    Article  PubMed  Google Scholar 

  69. Meijer JA, le Cessie S, van den Hout WB, Kievit J, Schoones JW, Romijn JA, Smit JW. Calcitonin and carcinoembryonic antigen doubling times as prognostic factors in medullary thyroid carcinoma: a structured meta-analysis. Clin Endocrinol. 2010;72(4):534–42. https://doi.org/10.1111/j.1365-2265.2009.03666.x.

    Article  CAS  Google Scholar 

  70. Laure Giraudet A, Al Ghulzan A, Auperin A, Leboulleux S, Chehboun A, Troalen F, Dromain C, Lumbroso J, Baudin E, Schlumberger M. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol. 2008;158(2):239–46. https://doi.org/10.1530/eje-07-0667.

    Article  PubMed  Google Scholar 

  71. Giraudet AL, Vanel D, Leboulleux S, Auperin A, Dromain C, Chami L, Ny Tovo N, Lumbroso J, Lassau N, Bonniaud G, Hartl D, Travagli JP, Baudin E, Schlumberger M. Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels. J Clin Endocrinol Metab. 2007;92(11):4185–90. https://doi.org/10.1210/jc.2007-1211.

    Article  CAS  PubMed  Google Scholar 

  72. Skoura E, Datseris IE, Rondogianni P, Tsagarakis S, Tzanela M, Skilakaki M, Exarhos D, Alevizaki M. Correlation between calcitonin levels and [(18)F]FDG-PET/CT in the detection of recurrence in patients with sporadic and hereditary medullary thyroid cancer. ISRN Endocrinol. 2012;2012:375231. https://doi.org/10.5402/2012/375231.

    Article  PubMed  PubMed Central  Google Scholar 

  73. de Baere T, Auperin A, Deschamps F, Chevallier P, Gaubert Y, Boige V, Fonck M, Escudier B, Palussiere J. Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases. Ann Oncol. 2015;26(5):987–91. https://doi.org/10.1093/annonc/mdv037.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Papotti M, Olivero M, Volante M, Negro F, Prat M, Comoglio PM, DiRenzo MF. Expression of hepatocyte growth factor (HGF) and its receptor (MET) in medullary carcinoma of the thyroid. Endocr Pathol. 2000;11(1):19–30.

    Article  CAS  PubMed  Google Scholar 

  75. Plaza-Menacho I, Mologni L, McDonald NQ. Mechanisms of RET signaling in cancer: current and future implications for targeted therapy. Cell Signal. 2014;26(8):1743–52. https://doi.org/10.1016/j.cellsig.2014.03.032.

    Article  CAS  PubMed  Google Scholar 

  76. Schlumberger M, Bastholt L, Dralle H, Jarzab B, Pacini F, Smit JW. 2012 European thyroid association guidelines for metastatic medullary thyroid cancer. Eur Thyroid J. 2012;1(1):5–14. https://doi.org/10.1159/000336977.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Links TP, Verbeek HH, Hofstra RM, Plukker JT. Endocrine tumours: progressive metastatic medullary thyroid carcinoma: first- and second-line strategies. Eur J Endocrinol. 2015;172(6):R241–51. https://doi.org/10.1530/eje-14-0726.

    Article  CAS  PubMed  Google Scholar 

  78. Hadoux J, Pacini F, Tuttle RM, Schlumberger M. Management of advanced medullary thyroid cancer. Lancet Diabetes Endocrinol. 2016;4(1):64–71. https://doi.org/10.1016/s2213-8587(15)00337-x.

    Article  CAS  PubMed  Google Scholar 

  79. Verbeek HH, Alves MM, de Groot JW, Osinga J, Plukker JT, Links TP, Hofstra RM. The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells. J Clin Endocrinol Metab. 2011;96(6):E991–5. https://doi.org/10.1210/jc.2010-2381.

    Article  CAS  PubMed  Google Scholar 

  80. Fox E, Widemann BC, Chuk MK, Marcus L, Aikin A, Whitcomb PO, Merino MJ, Lodish M, Dombi E, Steinberg SM, Wells SA, Balis FM. Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin Cancer Res. 2013;19(15):4239–48. https://doi.org/10.1158/1078-0432.ccr-13-0071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Moura MM, Cavaco BM, Leite V. RAS proto-oncogene in medullary thyroid carcinoma. Endocr Relat Cancer. 2015;22(5):R235–52. https://doi.org/10.1530/erc-15-0070.

    Article  CAS  PubMed  Google Scholar 

  82. Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Karlin N, Sideras K, Morris JC 3rd, McIver B, Hay I, Fatourechi V, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Cher Goh B, Isham CR, Harris P, Erlichman C. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab. 2014;99(5):1687–93. https://doi.org/10.1210/jc.2013-3713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Schlumberger M, Jarzab B, Cabanillas ME, Robinson B, Pacini F, Ball DW, McCaffrey J, Newbold K, Allison R, Martins RG, Licitra LF, Shah MH, Bodenner D, Elisei R, Burmeister L, Funahashi Y, Ren M, O'Brien JP, Sherman SI. A phase II trial of the multitargeted tyrosine kinase inhibitor Lenvatinib (E7080) in advanced medullary thyroid cancer. Clin Cancer Res. 2016;22(1):44–53. https://doi.org/10.1158/1078-0432.ccr-15-1127.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Endocrine Unit, Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University, Athens, Greece

    M. Alevizaki M.D., Ph.D., K. Saltiki, G. Simeakis & T. Pappa

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  1. M. Alevizaki M.D., Ph.D.
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  2. K. Saltiki
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  3. G. Simeakis
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  4. T. Pappa
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  1. Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland

    Luca Giovanella

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Alevizaki, M., Saltiki, K., Simeakis, G., Pappa, T. (2018). Medullary Thyroid Carcinoma (MTC): Diagnosis, Treatment and Follow-Up. In: Giovanella, L. (eds) Atlas of Thyroid and Neuroendocrine Tumor Markers. Springer, Cham. https://doi.org/10.1007/978-3-319-62506-5_8

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