Multiple endocrine neoplasia type 2 surgery

{{}} Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Surgery

Prophylactic or Precocious Thyroidectomy in RET Gene Carrier

• Prophylactic thyroidectomy is advised in gene carriers to guarantee a definitive cure in these subjects. Four different risk levels (from A, the lowest, to D the highest) for RET mutations have been suggested by the American Thyroid Association task force, which developed the most recent guidelines for the management of MTC patients. According to these guidelines, these levels of risk, which are related to the clinical aggressiveness of the corresponding MTC, should be taken into consideration when planning surgical treatment. In particular patients with a level D, RET mutation (i.e., Met918Thr) should be treated as soon as possible in the first year of life; patients with level B and C mutations (located in exons 10, 11, 13, 14, and 15) should be operated on before 5 years of age; only for patients with a level A mutation (exon 8 and 5 mutations), total thyroidectomy can be delayed after five years of age or until the CT positivity.
• Recently, some evidences in big series of RET gene carriers demonstrated that gene carriers with undetectable levels of basal CT have an almost null risk to have already developed the MTC. Moreover, a serum Ct <30–40 pg/mL is always associated to an intrathyroidal micro-MTC without any evidence of lymph node metastases. Taking into account these observation, Elisei et al. designed a study in which they operated on only RET gene carriers on the basis of basal and stimulated CT. According to their results, the time of surgical treatment could be personalized and safely planned when the stimulated serum CT becomes positive at the annual control, independently from the type of RET mutation and its associated level of risk. Of course, both cysteine RET mutations and older age are risk factors for having an earlier positive result for either basal or Pg-stimulated serum CT. For these reasons, the follow-up controls should be more or less frequent in cysteine or noncysteine RET-mutated gene carriers, respectively. This strategy obviously implies a high compliance of theRET gene carriers to the scheduled followup with the advantage that young children can be treated later, sometime even after the puberty, close to the adulthood.