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The synthesis of aldos- terone by the adrenal cortex: two zones (fasciculata and glomentlosa) possess one enzyme for 1III-, 18-hydroxylation and al- dehyde synthesis. J Biol Chem 261:3556- 3562. Yanagibashi K, Kobayashi Y, Hall PF: 1990. Ascorbate as a source of reducing equiva- lents for the synthesis of aldosterone. Bio- them Biophys Res Commun 170: 1256 1262. TEM The Practical Management of Multiple Endocrine Neoplasia Diana L. Learoyd, Stephen and Bruce G. Robinson M. Twigg, Debbie J. Marsh, Advances in the identification and localization of the abnormal genes in the multiple endocrine nwplasia syndromes have provided new methods of identifying “ at risk” individuals in these families. Genetic testing using linkage analysis in multiple endocrine neoplasia (MEN) 1 and direct mutation analysis of the RET protooncogene in MEN 2 is now available for these disorders. New management issues for these disorders have resulted, and a practical approach to these issues is discussed. (Trends Endocrinol Metab 1995;6:273-278). The authors are at the Kolling Institute of Medical Research (D.L.L., S.M.T., D.J.M., B&R.), Following identification of a gene car- and the Department of Endocrinology (D.L.L., S.M.T., B.G.R.), at Royal North Shore Hospital, rier, specific organ screening should fol- St. Leonards, New South Wales 2065, and the University of Sydney (D.L.L., S.M.T., D.J.M., low in an attempt to detect and treat B.G.R.), Sydney, New South Wales 2006, Australia. tumors at their earliest stage. The com- There have been several recent advances in the understanding of the pathogenesis of the multiple endocrine neoplasia (M EN) syndromes. These new findings have subsequently been applied to iden- tification of disease gene carriers in these syndromes. A number of new man- agement issues have resulted and new guidelines are being formulated to mon- itor the expression of the disease pheno- type. In this review, we present a practi- cal approach to the investigation and management of families with MEN type 1 or 2. Earlier reviews of MEN 1 and MEN 2 in this journal preceded recent genetic advances in both of these condi- tions (Marx 1989, Gage1 1991). * Multiple Endocrine Neoplasia Type 1 M EN 1 is an autosomal dominant syn- drome characteristically involving tu- mors of the parathyroid glands, pancre- atic islet cells, and anterior pituitary. The propensity for specific organ in- volvement tends to be consistent in any one family (Skogseid et al. 1991). In con- trast to sporadic (nonfamilial) endocrine tumors in these involved tissues, tumors in MEN 1 are more often multicentric, are commonly associated with hyperpla- sia, and have a higher rate of recurrence following treatment. Genetic Screening in M ultiple Endocrine Neoplasia Ty pe 1 The gene segregating with the clinical defects found in MEN 1 is believed to be a tumor suppressor gene that maps to a 900-kb region on the long arm of chro- mosome 11 at 1 lq13 (Weber et al. 1994). Loss of heterozygosity at this site has been detected in 70% of tumor tissue samples studied in MEN 1. The disorder is autosomal dominant, and offspring of an affected individual have a 50% chance of inheriting the disease pheno- type. Genetic screening for this disease is performed by linkage analysis. In a family in which at least two individuals are affected and there are informative markers flanking the M EN1 locus, risk estimates of greater than 99.5% for car- rying the defective gene can be given (Larsson et al. 1992). TEM Vol. 6, No.8, 1995 01995, Elsevier Science Inc., 1043-2760/95/$9.50 SSDI 1043-2760(95)00151-4 273