GENETIC TESTING IN THE DIAGNOSIS AND MANAGEMENT OF MULTIPLE ENDOCRINENEOPLASIA TYPE-II

Purpose: To review significant advances in the early diagnosis and tre atment of medullary thyroid carcinoma in patients with the multiple en docrine 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 an d DNA analysis in the MEN II syndromes. Study Selection: Articles on f amiliar and sporadic forms of medullary thyroid carcinoma; pentagastri n-calcitonin determination; and genetic testing. Data Extraction: Info rmation from recent studies on 1) the usefulness and limitations of ge netic testing, especially DNA and linkage analysis, in the early diagn osis 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 mo st of the morbidity and mortality among patients with the familiar med ullary thyroid carcinoma syndromes. Multiple endocrine neoplasia IIa a nd IIb and familiar medullary thyroid carcinoma are inherited conditio ns with autosomal dominance and incomplete penetrance. Traditionally, diagnosis of and screening for these conditions have been done using p entagastrin stimulation tests and plasma calcitonin determinations. Re cent 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 protoonc ogene are responsible for MEN IIa and IIb and familial non-MEN medulla ry thyroid carcinoma. Thus, genetic testing can identify affected memb ers of a kindred and will probably lead to early thyroidectomy and pos sible cure for gene carriers. Conclusions: Early studies confirm the u sefulness of DNA analysis in the diagnosis and treatment of patients w ith familial forms of medullary thyroid carcinoma. We review changes i n the diagnosis and treatment of these patients and offer a strategy f or operative intervention based on results of genetic testing.