Concepts for screening and diagnostic follow-up in multiple endocrine neoplasia type 1 (MEN1)[*]

Summary:

The recent identification of MEN1 gene mutations as the molecular cause of familial multiple endocrine neoplasia type 1 syndrome (MEN1) has had a significant impact on clinical patient care. In the following consensus statement we will present recommendations for clinical screening and follow-up in patients and relatives with suspected or established MEN1 syndrome. MEN1 mutational analysis should be performed in individuals with newly diagnosed MEN1-typical endocrine neoplasia (e.g., primary hyperparathyroidism, gastroenteropancreatic tumor, pituitary adenoma) if additional diagnostic criteria are met (e.g., age <40 years; positive family history; multifocal or recurrent neoplasia; two or more organ systems affected). Genetic family screening is advisable in first degree relatives of MEN1 patients during early adolescence to reliably assess future MEN1 disease risk. In symptomatic individuals carrying MEN1 germ line mutations, annual clinical and biochemical (calcium, PTH, gastrin, prolactin) follow-up as well as routine pancreatic and pituitary imaging may be complemented as individually needed. In contrast, relatives without family-specific MEN1 mutation do not require routine follow-up. Diagnostic procedures and treatment in symptomatic MEN1 mutation carriers and patients may differ from that in sporadic endocrine neoplasia, calling for individual management. Genetic counselling and dedicated endocrine surgery should be intergral parts of current medical care in MEN1 syndrome.

Key words:

Multiple endocrine neoplasia type 1 - MEN1 - tumor suppressor - gene screening

1 ^* In collaboration with the German MEN1 study group, listed in the appendix

References

• 1 Agarwal K S, Guru S C, Heppner C, Erdos M R, Collins R M, Park S Y. Menin interacts with the AP1 transcription factor JunD and represses JunD activated transcription.  Cell. 96 143-152 1999; 
• 2 Chandrasekharappa S C, Guru S C, Manickam P, Olufemi S-E, Collins F S, Emmert-Buck M R. Positional cloning of the gene for multiple endocrine neoplasia-type 1.  Science. 276 404-407 1997; 
• 3 Guru S C, Goldsmith P K, Burns A L, Marx S J, Spiegel A M, Collins F S. Menin, the product of the MEN1 gene, is a nuclear protein.  Proc Natl Acad Sci USA. 95 1630-1634 1998; 
• 4 Karges W, Maier S, Wissmann A, Dralle H, Dosch H M, Boehm B O. Primary structure, gene expression and chromosomal mapping of rodent homologs of the MEN1 tumor suppressor gene.  Biochim Biophys Acta. 1446 286-294 1999; 
• 5 Komminoth P, Heitz P U, Klöppel G. Pathology of MEN-1: morphology, clinicopathologic correlations and tumour development.  J Int Med. 243 455-464 1998; 
• 6 Larsson C, Skogseid B, Oeberg K, Nakamura Y, Nordenskjoeld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma.  Nature. 332 85-87 1988; 
• 7 Teh B T. Recent advances in multiple endocrine neoplasia type 1.  Current Opinion in Endocrinology and Diabetes. 5 35-39 1998; 
• 8 Thakker R V. Multiple endocrine neoplasia-syndromes of the twentieth century (editorial).  J Clin Endocrinol Metab. 83 2617-2620 1998; 
• 9 The European Consortium on MEN1 . Identification of the multiple endocrine neoplasia type 1 (MEN1) gene.  Hum Molec Genet. 6 1177-1183 1997; 
• 10 Zahrani A A, Levine M A. Primary hyperparathyroidism.  Lancet. 349 1233-1238 1997; 

Appendix

Members of the German MEN1 Study Group

(centers in alphabetical order) Berlin: H. Gerl; Bern: B. Göke; Chemnitz: A. Graupner; Düsseldorf: P. Goretzki, C. Dotzenrath, Essen: M. Bockhorn, A. Hahn; Halle: H. Dralle; Hamburg: W. Höppner; Heidelberg: A. Clemens, T. Schilling; F. Raue; Kiel: G. Klöppel; H. Mönig; Leipzig: A. Miedlich; Lübeck: T. Parlowsky; Mainz: O. Zwermann, A. Engelbach; Marburg: B. Simon, R. Arnold; D. Bartsch, M. Rothmund; München: J. Huber, F. Spelsberg; T. Strom; O. E. Janssen; J. Pickel, L. Schaaf; Tübingen: R. Lamberts; A. Rettig; Ulm: W. Karges, B. O. Boehm.

Information on MEN1 patient registration and documentation forms of patient consent

Deutsches MEN1 RegisterMax-Planck-Institut für PsychiatrieKraepelinstr. 10D-80804 MünchenTel./Fax: [phone]e-mail: [e-mail]

1 ^* In collaboration with the German MEN1 study group, listed in the appendix