correct answer
c total thyroidectomy
MEN 2 is caused by activating germline missense variants in the RET proto-oncogene,
[1] and the definitive diagnosis is made by RET sequencing (positive in 98 % of cases). A complete curation of close to 200 RET germline variants reported (up to 2022 and including single or multiple variants, missense, duplications, insertions or deletions, and chromosomal rearrangements), are hosted in the continually updated
ARUP MEN 2 database[2].
Medullary thyroid cancer is highly associated with MEN 2. There are variants of MEN 2: MEN 2A (95% of cases) and MEN 2B (5%). MEN 2A is further subdivided into four phenotypes: Classical MEN 2A, MEN 2A with cutaneous lichen amyloidosis, MEN 2A with Hirschsprung’s disease, and Familial MTC (FMTC). The MTC risk is roughly:
- Classical MEN 2A - MTC 90%
- MEN 2A with CLA - MTC 95%
- MEN 2A with HD - MTC 80%
- MEN 2B (5%) - MTC 100%
The management of MEN2-related MTC depends on a) confirmation of a pathogenic RET variant, (2) classification of the MTC risk group by RET variant genotype, and (3) the calcitonin level. Surgery is the only cure for MTC, and the goal of “prophylactic thyroidectomy” is the, ‘
removal of the thyroid before MTC develops or while it is clinically unapparent and confined to the gland’, according to the ATA (American Thyroid Association) guidelines for MTC.
The MTC risk groups are highest, high, and moderate, based on the specific RET variant.
The
highest risk group should undergo total thyroidectomy within the first year of life, perhaps even in the first months of life, despite an increased risk of complications due to the young age.
In the
high risk group thyroidectomy is recommended at age 5 years or earlier based on the detection of elevated serum calcitonin levels.
For the
moderate risk group, the timing of thyroidectomy should be when serum calcitonin level becomes elevated.
The timing of prophylactic thyroidectomy in the
moderate risk group is especially challenging, since there is substantial variability in the age of MTC onset, even among patients with the same variant. Therefore, the optimal scheduling of thyroidectomy in this group is highly dependent on measuring the calcitonin level. In a study of 170 children with a preoperative calcitonin level below 30 pg/mL, all were cured after thyroidectomy regardless of MTC risk group.
[3] A Norwegian study showed similar results and found that all patients having thyroidectomy with a calcitonin level below 40 pg/mL were biochemically cured.
[4]
