FROM MEDICAL HISTORY AND BIOCHEMICAL TESTS TO PRESYMPTOMATIC TREATMENT IN A LARGE MEN 2A FAMILY

An extensive study was published in 1959 in the Netherlands on a large family, which initially attracted attention because of a family histo ry of attacks of shaking. Clinical investigation revealed phaeochromoc ytomas in four family members. In 1975, the family was identified to b e a MEN 2A family, and since then, the members were examined annually using measurement of catecholamine metabolites in 24-h excreted urine and C-cell stimulation tests, In 1993, the RET proto-oncogene on chrom osome 10q11 was found to be associated with MEN 2A and a specific muta tion in this gene was identified in the family. In this family, 32 MEN 2A patients were detected. Since screening started in 1975, no patien t died of phaeochromocytoma; however, two patients died of metastasize d medullary thyroid carcinoma (MTC) (mean age 46 years). Twelve patien ts were operated on for phaeochromocytoma, and 13 for MTC. The results of DNA-analysis revealed the failures of the biochemical tests to ide ntify affected family members. Six disease gene carriers with normal C -cell stimulation test results appeared to have small multifocal MTCs. Two carriers with normal excretion levels of catecholamines had a sma ll phaeochromocytoma. DNA-analysis enables the unambiguous diagnosis o f MEN 2A gene carriership, allowing presymptomatic surgery for MTC.