Familial Cancer

, Volume 11, Issue 2, pp 157–165 | Cite as

Hereditary medullary thyroid carcinoma: the management dilemma

  • Ping Zhou
  • Jian LiuEmail author
  • Shao-Wen Cheng
  • Bing Wang
  • Rong Yang
  • Ling Peng


Hereditary medullary thyroid carcinoma (hereditary MTC) is a rare malignancy, accounting for 25–30% of all MTC. It occurs as part of multiple endocrine neoplasia type 2 (MEN 2). Autosomal dominant gain-of-function mutations in the RET proto-oncogene is the cause of the disease, in which the common mutations are codons 609, 611, 618, 620, 630, 634 and 918. In recent years, the spectrum of RET gene mutations has changed. The classical mutations reduced, whereas the less aggressive mutations increased. Hereditary MTC is a time-dependent disease. Stages of the disorder at diagnosis can significantly influence survival rates. Based on the genotype–phenotype, RET mutations have been classified into four risk levels by American Thyroid Association (ATA) at 2009. The classification system guides the hereditary MTC management, including risk assessment, biochemical screenings and surgical intervention. Though the application of genetic testing and codon-specific phenotypes in hereditary MTC diagnosis is effective with high accuracy, there are some difficulties in implementing RET gene testing as a routine for MTC diagnosis. And most of carriers with RET mutations did not undergo thyroidectomy at the age recommended by the ATA guidelines. The aim of the study is to review the hereditary MTC and discuss the management dilemma.


Hereditary medullary thyroid carcinoma RET proto-oncogene Mutation Management Prophylactic thyroidectomy 



Rearranged during transfection

Hereditary MTC

Hereditary medullary thyroid carcinoma


Multiple endocrine neoplasia type 2


American Thyroid Association


Medullary thyroid carcinoma


C-cell hyperplasia






Familial MTC


Variant of unknown significance


Hirschsprung disease



We are deeply appreciative of our mentors and friends for guide and help, including Zhi-Min Ma, Wen-He Zhao, Wei-Bing Wang and Xin-Xing Duan. And we thank the following institutions which provided valuable information: Department of Surgical oncology and Pathology of the first affiliated hospital of Zhejiang university school of medicine.

Conflict of interest

There are no conflicts of interest.


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Ping Zhou
    • 1
  • Jian Liu
    • 4
    Email author
  • Shao-Wen Cheng
    • 2
  • Bing Wang
    • 1
  • Rong Yang
    • 1
  • Ling Peng
    • 3
  1. 1.Department of Surgical Oncology, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Trauma Center, The Affiliated Hospital of Hainan Medical CollegeHaikouChina
  3. 3.Department of Medical Oncology, The First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  4. 4.Department of Surgical OncologyHangzhou Hospital of Traditional Chinese MedicineHangzhouChina

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