Genotype - phenotype correlations and timing of prophylactic thyroidectomy in patients with familial medullary thyroid carcinoma
J. Podoba, M. Podobová, M. Grigerová, E. Weismanová & K. Závodná
Background: Recommendations on the timing of prophylactic thyroidectomy (PTTE) in patients with familial medullary carcinoma (FMTC) are based on classification of RET mutations into four risk levels according to genotype - phenotype correlations. In clinical practice it is/was not always possible to fulfill the recommended timing of PTTE.
Objectives: To study the clinical course of FMTC patients with various RET mutations who were operated with a time delay against recommended timing.
Patients and methods: Retrospective analysis of clinical course in 42 RET mutation carriers from 12 FMTC and MEN 2A families.
Results: ###25 high risk mutation carriers (codone 634) undergone an operation at the age 1348 years. In all but one aged 13 years MTC was histologically confirmed. 30% of them continued to suffer from persistent disease after delayed operation and 70% achieved remission. One patient operated after 40 years of age died from the progression of MTC after 6 years.
###12 patients with low risk mutations (codone 618 and 620) had surgery aged between 1660 years. In all but one aged 52 years MTC was verified. In the whole group of patients remission was achieved only in 58%.
In 3 least high risk mutation carriers (codone 791) aged 36, 40 and 42 years respectively TTE was indicated after possitive calcium stimulation test. It was completelly prophylactic, only C-cell hyperplasia was revealed.
Conclusions: Our data confirm the necessity to fulfill the guidelines on the timing of PTTE at the age of 5 years for high risk mutation (codone 634) carriers, while in least high risk mutation carriers surgery may be postponed untill an abnormal stimulation test result is observed (delay even to young adulthood). Our results in a small group of low risk mutation carriers (codones 618 and 620) suggest the need to be much more radical. In the case of negative results of thyroid USG and calcitonin stimulation test PTTE can be postponed no later than to the age of 10 years.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector