Multiple endocrine neoplasia: types 1 and 2

Abstract

Multiple endocrine neoplasia type 1 (MEN 1) and type 2 (MEN 2) are autosomal-dominantly inherited syndromes where highly penetrant germline mutations predispose patients to the development of tumours in hormone-secreting cells. In the case of MEN 1, loss-of-function germline mutations in the tumour suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumours, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumours. In the case of MEN 2, gain-of-function germline mutations clustered in specific codons of the RET proto-oncogene increase the risk of developing medullary thyroid carcinoma (MTC), phaeochromocytoma and parathyroid tumours. Offering RET testing is best practice for the clinical management of patients at-risk of MEN 2, and MEN 2 has become a classic model for the integration of molecular medicine into patient care. Prophylactic thyroidectomy in an asymptomatic RET mutation carrier to address the risk of developing MTC can prevent or cure this malignancy. No similar preventative strategies can be employed to prevent or cure MEN 1-associated tumours. Genetic testing for MEN 1 is therefore both more complex due to a general lack of mutational hotspots, and the benefit to patients is less straight forward. While a number of genotype-phenotype correlations exist in MEN 2, providing further rationale for performing genetic testing in this condition, these correlations are absent in MEN 1. This review summarises our current knowledge of these two syndromes with emphasis on those aspects with specific relevance to the otorhinolaryngologist.