[Preventive thyroidectomy].

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy that occurs in hereditary (25%) and sporadic (75%) clinical settings. MTC is present in all patients with the multiple endocrine neoplasia type 2 syndromes. MTCs produce calcitonin, the measurement of which can indicate the presence of tumors in people who are at risk and the effectiveness of therapy in treated patients. Surgical cure is possible in young patients with multiple endocrine neoplasia type 2 who undergo preventative thyroidectomy (approximately 50% of patients who are diagnosed with a palpable thyroid mass) and in some patients with recurrent nodal metastatic disease in the neck. Mortality from MTC is caused by tumor invasion of the trachea, great vessels in the neck, or mediastinum or by the effects of distant metastatic disease. Surgery for cervical recurrence can prevent death from tracheal invasion. The role of radiation therapy is not well defined. There is no effective systemic therapy for MTC. Activating mutations in a tyrosine kinase receptor gene (RET) are present in most MTCs, and experience with tyrosine kinase inhibitors and other agents in clinical trials is critical for the identification of effective systemic treatment.

Carcinoma, Medullary↗

PubMed2003

Segregation of the V804L mutation and S836S polymorphism of exon 14 of the RET gene in an extended kindred with familial medullary thyroid cancer.

In multiple endocrine neoplasia type 2A (MEN 2A) and familial medullary thyroid cancer (FMTC), the majority of germline mutations are restricted to specific positions in exons 10 and 11 of the RET gene. However, germline mutations may very occasionally occur in other exons, including exon 14 of the RET gene. Interestingly, an increased frequency of a rare germline sequence variant of the RET exon 14, S836S, has been detected in patients with sporadic medullary thyroid cancer (MTC), and this variant has been proposed to play a role in the genesis of MTC and, perhaps, FMTC. In this study we report the segregation of a germline V804L mutation and a germline sequence variant S836S in exon 14 of the RET gene in an extended Hungarian FMTC kindred comprising 80 individuals of four generations. Molecular analysis of the RET gene was performed by direct DNA sequencing in 23 family members, of whom 12 had the V804L mutation, three had the V804L mutation and S836S polymorphism in separate alleles, and six had the S836S polymorphism, all in heterozygous forms. Two of the family members had neither mutation nor polymorphism of the RET gene. Three of the family members who had the V804L mutation and one member who could not be tested for mutation were operated for non-metastatic MTC, while one member with MTC who had the V804L mutation refused surgery. In all patients affected with MTC, the disease developed relatively late in life and never caused death. None of the other family members carrying the V804L mutation and/or the S836S polymorphism had clinical or biochemical evidence of MTC. These observations suggest that the co-existence of the V804L mutation and S836S polymorphism in separate alleles does not seem to aggravate the relatively low-risk disease phenotype characteristic in most patients with codon 804 mutations of the RET exon 14.

Carcinoma, Medullary↗