Multiple endocrine neoplasia (MEN)

R V Thakker

Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7LJ

Summer School 13-16 July 2004
St Anne's College, Oxford University, UK

MEN is characterized by the occurrence of tumours involving two or more endocrine glands, and two major forms, referred to as MEN1 and MEN2, are recognised. MEN1 is characterised by parathyroid, pancreatic islet, and anterior pituitary tumours, whilst MEN2 is characterised by medullary thyroid carcinoma (MTC) in association with phaeochromocytoma, and three clinical variants referred to as MEN2A, MEN2B, and MTC only are recognized. All these forms of MEN may be inherited as autosomal dominant syndromes. The MEN1 gene is on chromosome 11q13 and about 300 MEN1 mutations have been identified. These are of diverse types and are scattered throughout the coding region. There is also a lack of genotype-phenotype correlation. All these findings make it difficult to implement MEN1 mutational analysis in the clinical setting. The situation in MEN2 is more straightforward. The gene causing all three MEN2 variants is located on chromosome 10cen-10q11.2, and is the c-ret proto-oncogene which encodes a tyrosine kinase receptor with cadherin-like and cysteine-rich extracellular domains, and a tyrosine kinase intracellular domain. Specific mutations of c-ret have been identified for each of the three MEN2 variants and mutational analysis has been used in the diagnosis and management of patients and families with the MEN2 variants.

References

1. Thakker RV. Multiple Endocrine Neoplasia Type 1. In Endocrinology 4th edition. (Ed: LJ DeGroot and JL Jameson). 2001 : pp 2503-2517 (publishers: WB Saunders Company, Philadelphia, USA).

2. Thakker RV. 1998. Multiple Endocrine Neoplasia – Syndromes of the twentieth century. Journal of Clinical Endocrinology & Metabolism 83: 2617-2620.

3. Pannett AAJ and Thakker RV. 1999. Multiple Endocrine Neoplasia Type 1 (MEN1) gene. Endocrine Related Cancer 6: 449-473.

4. Gagel RF. Multiple Endocrine Neoplasia Type 2. In Endocrinology 4th edition. Ed. LJ DeGroot and JL Jameson. 2001. pp2518-2532 (publishers WB Saunders Company, Philadelphia, USA).

5. Eng C. The RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung disease. New England Journal of Medicine. 1996. 335:943-951.

The opinions expressed in this paper are those of the speaker and do not necessarily reflect the views of the Society

Revised: 05-Nov-2004