DIAGNOSIS AND MANAGEMENT OF PHEOCHROMOCYTOMAS IN PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE 2-RELEVANCE OF SPECIFIC MUTATIONS IN THE RET PROTOONCOGENE

It has been suggested that specific mutations in the RET proto-oncogen e correlate with clinical manifestation of the multiple endocrine neop lasia type 2 (MEN 2) syndrome, We retrospectively analyzed 61 patients with MEN 2, 28 with associated pheochromocytoma, regarding the releva nce of specific mutations in the RET proto-oncogene and the diagnostic sensitivity of catecholamine screening and localization procedures. T he present study shows that the position of the RET mutation is relate d to disease phenotype; codon 634 mutations are predictive of families predisposed to pheochromocytoma. In 18% of our patients. the diagnosi s of pheochromocytoma preceded detection of medullary thyroid carcinom a. Therefore, mutation analysis of the RET gene should be performed in apparently ''sporadic'' cases of pheochromocytoma to confirm or exclu de MEN 2. The most sensitive biochemical marker for pheochromocytoma i n MEN 2 is 24-h urinary epinephrine excretion. Computed tomography, ma gnetic resonance imaging and MIBG scintigraphy are all highly sensitiv e methods to localize pheochromocytoma. We conclude that, in all famil ies with MEN 2, mutational analysis of the RET proto-oncogene should b e performed, both to identify gene carriers for MEN 2 and to identify specific mutations that are more strongly associated with pheochromocy toma.