Is thyroidectomy necessary in RET mutations carriers of the familial medullary thyroid carcinoma syndrome?

Abstract

BACKGROUND The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary thyroid carcinoma (MTC). In 4 of 10 families, mutation in exon 10 was found in codon 611. RESULTS One hundred fifty persons belonging to 30 families were tested, of which 10 families were carriers of RET mutation in exon 10. In 1 of these families with MTC only, 2 brothers were gene carriers of a RET codon 611 mutation and lived without any sign of MTC. One is aged 79 years, and the other died at the age of 71 of other causes. CONCLUSIONS The results indicate that the gene carrier in families with MTC without other endocrine tumors (FMTC) exhibits a highly variable disease course. A 611 codon mutation is most often a rather mild and slow progression form of MTC. Because 2 gene carriers were still alive at age 70 years without showing any sign of the disease, it is tempting to ask if all gene carriers with a 611 codon mutation without other endocrine tumors should be operated on, and if so, at what age? In the authors' opinion, more information is needed to be able to answer these questions. The current guidelines for treatment of patients with hereditary MTC are discussed. Cancer 2000;89:863–7. © 2000 American Cancer Society.

Familial prevalence and age of RET germline mutations: implications for screening

“…Considering our data, many of the germline mutations running in German RET families obviously were created by spontaneous mutation many decades, if not centuries ago. In keeping, rare literature reports ( Table 1) [12][13][14][15][16][17][18][19][20] suggested that the germline mutation in some RET families can be fairly old, existing since 1896 at the latest in a Swedish RET family harbouring the C618S mutation, 15 and possibly since 1865 at least in a German RET family with the C634W mutation. 20 Rigorous ascertainment of RET carriers with solitary, seemingly sporadic tumours, early family screening, early surgical intervention, and continual hormonal and radiological surveillance, in all likelihood, minimize differential effects that detection bias otherwise might have had on the identification of carriers with different RET mutations.…”

Clinical and Oncological Features of Children and Young Adults with Multiple Endocrine Neoplasia Type 2A

“…The diagnosis was made concomitantly to MTC in one case (25 years of age) and 9, 12, and 15 years after the thyroid tumor (26,30, and 31 years of age).…”

“…Theoretically, if thyroid surgery is performed before the neoplastic transformation from C-cell hyperplasia to MTC, the prophylactic procedure can be limited to the thyroid gland. When performed by an experienced endocrine surgeon, this intervention presents few complications and a high rate of biochemical cure (18)(19)(20)(21)(22)(23)(24)(25)(26). Indeed, recent studies evaluating the follow-up of children who underwent total thyroidectomy prophylactically have reported a lower incidence of persistent or recurrent disease (21)(22)(23).…”

Advances in the management of hereditary medullary thyroid cancer

“…All three patients could have acquired additional, albeit unrecognized, germline or somatic mutations. Variation in expression and penetrance has been described for RET codons 611, 618, 790, 791 and 804 [12, 41–44]. These examples epitomize how unreliable individual predictions of phenotype can be when these are based solely on RET genotype.…”