Multiple Endocrine Neoplasia Type 2
Table 5. American Thyroid Association Medullary Thyroid Cancer Risk Stratification and Management Guidelinesa
|Risk level||Mutated Codon(s)||Age ofRETTesting||Timing of Prophylactic Thyroidectomy|
|a Adapted from Kloos et al.|
|b These mutations had not been reported at the time of the 7th International Workshop.|
|c Criteria include a normal annual basal and/or stimulated serum count, normal annual neck ultrasound, less aggressive medullary thyroid cancer family history, and family preference.|
|D||883, 918, and compound heterozygotes V804M+E805K, V804M+Y806C, and V804M+S904C||ASAP and within the first y of life||ASAP and within the first y of life.|
|C||634||<3–5 y||Before age 5 y.|
|B||609b, 611, 618, 620, 630b, and compound heterozygote V804M+V778I||<3–5 y||Consider surgery before age 5 y. May delay surgery after age 5 y if criteria are met.c|
|A||768, 790, 791, 804, 891||<3–5 y||May delay surgery after age 5 y if criteria are met.c|
In a study of biochemical screening in a large family with MEN2A performed before mutation analysis became available, 22 family members without evidence of clinical disease had elevated calcitonin and underwent thyroidectomy. During a mean follow-up period of 11 years, all remained free of clinical disease, and 3 out of 22 had transient elevation of postoperative calcitonin levels. The use of biochemical screening is limited, however, by the lack of data on age-specific calcitonin levels in children under 3 years of age; caution should be used when interpreting these values in this age group.
A study of 93 patients with MEN2 from a Dutch tumor registry documented the importance of early prophylactic thyroidectomy. This group of patients represented all known Dutch patients with hereditary MTC; the majority of cases (67%) were codon 634 mutations; only 6% were MEN2B cases. Patients in this series were screened with either biochemical testing (pre-RET era) or RET mutation analysis. In both groups, patients who underwent surgery at a later age than recommended by current guidelines (see Table 5), but the percentage from the pre-RET era was significantly higher (96% vs. 69%, P = .004). Older age at prophylactic thyroidectomy was significantly associated with a higher risk of postoperative persistent/recurrent disease. Although there is concern that young age at total thyroidectomy is associated with higher risk of surgical complications, this study found no such evidence.