Prophylactic and Therapeutic Surgery in Familial Medullary Thyroid Cancer

  • Atakan Sezer
  • Mehmet Çelik


Medullary thyroid cancer (MTC) is a neuroendocrine malignancy, which originates from C cells (parafollicular) of the gland. MTC is inherited in autosomal dominant pattern in 20–25% of patients with MEN syndromes. Familial MTC (FMTC) is the most frequent type of MEN syndromes.

The most accepted approach for deciding surgical treatment of the disease based on the precise polymer mutation within the douse factor occurring within the family and blood serum calcitonin levels.

RET mutations may be classified as highest, high, and moderate risk, concerning the potential risk for native and distant MTC metastases at an early age. The advised temporal order of excision relies upon proof of age-dependent and codon-specific progression of early MTC.

In conclusion, patients with inherited MTC ought to experience age-suitable thyroidectomy in view of RET mutational status to evade recurrences.


Medullary thyroid cancer MEN syndromes Calcitonin RET mutation 


  1. 1.
    Cancer of the Thyroid Invasive: Trends in SEER Incidence and U.S. Mortality Using the Joinpoint Regression Program, 1975–2011(SEER) Stat version 8.1.2 Rate Session. Access the SEER 18 database at Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2012 Sub (2000–2010) - Linked To County Attributes - Total U.S., 1969–2011 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2013, based on the November 2012 submission.
  2. 2.
    Hadoux J, Pacini F, Tuttle RM, Schlumberger M. Management of advanced medullary thyroid cancer. Lancet Diabetes Endocrinol. 2016;4:64–71.CrossRefGoogle Scholar
  3. 3.
    Leboulleux S, Baudin E, Travagli J, Schlumberger M. Medullary thyroid carcinoma. Clin Endocrinol. 2004;61:299–310.CrossRefGoogle Scholar
  4. 4.
    Wells S, Asa S, Dralle H, Elisei R, Evans D, Gagel R, et al. Revised American Thyroid Association guidelines for the Management of Medullary Thyroid Carcinoma. Thyroid. 2015;25:567–610.CrossRefGoogle Scholar
  5. 5.
    Bockhorn M, Frilling A, Rewerk S, Liedke M, Dirsch O, Schmid K, et al. Lack of elevated serum Carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma. Thyroid. 2004;14:468–70.CrossRefGoogle Scholar
  6. 6.
    Redding A, Levine S, Fowler M. Normal preoperative calcitonin levels do not always exclude medullary thyroid carcinoma in patients with large palpable thyroid masses. Thyroid. 2000;10:919–22.CrossRefGoogle Scholar
  7. 7.
    Diez JJ, Iglesias P. Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma. Thyroid. 2004;14:984–5.PubMedGoogle Scholar
  8. 8.
    Heshmati HM, Hofbauer LC. Multiple endocrine neoplasia type 2: recent progress in diagnosis and management. Eur J Endocrinol. 1997;137:572–8.CrossRefGoogle Scholar
  9. 9.
    Schilling T, Burck J, Sinn HP, Clemens A, Otto HF, Hoppner W, et al. Prognostic value of codon 918 (ATG-->ACG) RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. Int J Cancer. 2001;95:62–6.CrossRefGoogle Scholar
  10. 10.
    Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93:682–7.CrossRefGoogle Scholar
  11. 11.
    Raue F, Frank-Raue K. Genotype-phenotype correlation in multiple endocrine neoplasia type 2. Clinics (Sao Paulo). 2012;67(Suppl 1):69–75.CrossRefGoogle Scholar
  12. 12.
    Imai T, Uchino S, Okamoto T, Suzuki S, Kosugi S, Kikumori T, et al. High penetrance of pheochromocytoma in multiple endocrine neoplasia 2 caused by germ line RET codon 634 mutation in Japanese patients. Eur J Endocrinol. 2013;168:683–7.CrossRefGoogle Scholar
  13. 13.
    Jasim S, Ying AK, Waguespack SG, Rich TA, Grubbs EG, Jimenez C, et al. Multiple endocrine neoplasia type 2B with a RET proto-oncogene A883F mutation displays a more indolent form of medullary thyroid carcinoma compared with a RET M918T mutation. Thyroid. 2011;21:189–92.CrossRefGoogle Scholar
  14. 14.
    Frank-Raue K, Rybicki LA, Erlic Z, Schweizer H, Winter A, Milos I, et al. Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. Hum Mutat. 2011;32:51–8.CrossRefGoogle Scholar
  15. 15.
    Cuccuru G, Lanzi C, Cassinelli G, Pratesi G, Tortoreto M, Petrangolini G, et al. Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma. J Natl Cancer Inst. 2004;96:1006–14.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Atakan Sezer
    • 1
  • Mehmet Çelik
    • 2
  1. 1.Department of SurgeryTrakya University Medical FacultyEdirneTurkey
  2. 2.Department of EndocrinologyTrakya University Medical FacultyEdirneTurkey

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