Prophylactic thyroidectomy in multiple endocrine neoplasia 2 (MEN2) patients with the C634Y mutation: A long-term follow-up in a large single-center cohort

Eur J Surg Oncol. 2019 Apr;45(4):625-630. doi: 10.1016/j.ejso.2018.09.002. Epub 2018 Oct 17.


Background: Medullary thyroid carcinoma (MTC) is the main cause of death in multiple endocrine neoplasia 2A (MEN2A) patients. It is therefore important to treat this disease at an early stage. The mutation in codon 634 is considered to be associated with an aggressive clinical course, whereas the C634Y mutation may result in a more indolent course. Prophylactic thyroidectomy is performed before thyroid disease occurs. However, controversy surrounds this disease regarding levels of calcitonin (Ct) and age. In this context, few studies have investigated this mutation over a long period.

Objective: To analyze a large cohort of patients with the C634Y mutation who received prophylactic thyroidectomy.

Materials and methods: In a group of 110 MEN2 patients, we analyzed those with the C634Y mutation who had received prophylactic thyroidectomy (absence of clinical and radiological thyroid disease) treated in a tertiary referral hospital between 1983 and 2016. MTC is related to age and Ct. Statistical analysis was performed using the χ2 test, partial correlations, and logistic regression.

Results: Fifty patients with a mean age of 12 ± 9 years were analyzed; 56% of these had MTC (100% stage I). There was no case of hypoparathyroidism or permanent recurrent damage. MTC was associated mainly with age (OR 1.38). One 5-year-old patient presented with MTC. Mean follow-up time was 16 ± 6 years, and no cases of recurrence were observed.

Conclusions: Performing prophylactic thyroidectomy in patients with the C634Y mutation allows us to cure the disease without causing long-term complications. Our results support the notion that age <5 years should be a criterion for carrying out prophylactic thyroidectomy in these patients.

Keywords: MEN2; Medullary thyroid carcinoma; Prophylactic; Thyroidectomy.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Calcitonin / blood
  • Carcinoma, Neuroendocrine / blood
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / prevention & control*
  • Carcinoma, Neuroendocrine / surgery*
  • Child
  • Child, Preschool
  • Follow-Up Studies
  • Humans
  • Multiple Endocrine Neoplasia Type 2a / blood
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Multiple Endocrine Neoplasia Type 2a / surgery*
  • Proto-Oncogene Proteins c-ret / genetics
  • Thyroid Neoplasms / blood
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / prevention & control*
  • Thyroid Neoplasms / surgery*
  • Thyroidectomy*
  • Time Factors
  • Young Adult


  • Calcitonin
  • Proto-Oncogene Proteins c-ret

Supplementary concepts

  • Thyroid cancer, medullary