Purpose: To review significant advances in the early diagnosis and treatment of medullary thyroid carcinoma in patients with the multiple endocrine neoplasia II (MEN II) syndromes, advances made possible by the application of recently discovered genetic information.
Data sources: Recently published English-language literature on linkage analysis and DNA analysis in the MEN II syndromes.
Study selection: Articles on familial and sporadic forms of medullary thyroid carcinoma; pentagastrin-calcitonin determination; and genetic testing.
Data extraction: Information from recent studies on 1) the usefulness and limitations of genetic testing, especially DNA and linkage analysis, in the early diagnosis of the familial form of thyroid carcinoma and 2) the correlation between the results of genetic testing and the results of biochemical screening.
Data synthesis: Medullary thyroid carcinoma accounts for most of the morbidity and mortality among patients with the familial medullary thyroid carcinoma syndromes. Multiple endocrine neoplasia IIa and IIb and familial medullary thyroid carcinoma are inherited conditions with autosomal dominance and incomplete penetrance. Traditionally, diagnosis and screening for these conditions have been done using pentagastrin stimulation tests and plasma calcitonin determinations. Recent genetic mapping, however, has assigned the genes responsible for these tumors to the pericentromeric region of chromosome 10. Available data suggest that mutations in exon 10, 11, or 16 of the RET proto-oncogene are responsible for MEN IIa and IIb and familial non-MEN medullary thyroid carcinoma. Thus, genetic testing can identify affected members of a kindred and will probably lead to early thyroidectomy and possible cure for gene carriers.
Conclusions: Early studies confirm the usefulness of DNA analysis in the diagnosis and treatment of patients with familial forms of medullary thyroid carcinoma. We review changes in the diagnosis and treatment of these patients and offer a strategy for operative intervention based on results of genetic testing.