Background: Medullary thyroid cancer (MTC) in MEN 2A is caused by mutations in RET. Guidelines (2001/2009/2015) recommend prophylactic total thyroidectomy (TT) based on mutation specific risk levels (ATA 2015: high/moderate).
Objective: The aim of this study was to analyse changes of age at TT, frequency of metastatic MTC (MMTC), and frequency of TT according to guidelines since introduction of RET testing in 1995.
Methods: Patients in publications from 19952014 aged 020 years with individual information on age at TT, histology, and RET-mutation, if available, were included. Patients were grouped according to publication year: groups A=19951999, B=20002004, C=20052009, and D=20102014. Median age at TT, rate of MMTC, and rate of TT according guidelines were compared in the four groups.
Results: In 110 publications 601 patients were identified (A=128, B=149, C=220, D=107). Overall, median age at TT was not different in the four groups (11, 11, 10, 8 years), while frequency of MMTC decreased significantly (A=17% vs D=5%, P<0.001). In ATA 2015 high risk mutation carriers (c634, c883; n=296) median age at TT decreased significantly in the four groups from 13, 11, 9 to 7 years (P<0.01) in parallel with a significant decrease of MMTC in group A vs. D (27% vs 8%, P<0.01). However, in this high-risk group, the rate of children thyroidectomised at latest with 5 years according to guidelines remained low (15%, 22%, 20%, 30%) despite genetic testing. In ATA 2015 moderate risk mutation carriers (all 11 other MEN2A causing mutations; n=263) median age at TT did not differ between groups (9, 11, 12, 10 years) in accordance with risk level specific age recommendations for TT.
Conclusion: Age at TT and MMTC rate decreased overall and in high risk mutations carriers. However, still 70% of high-risk mutation carriers are thyroidectomised beyond recommended age of 5 years.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology