Multiple endocrine neoplasia type 1 (MEN1)

MEN1 is inherited in an autosomal dominant manner. Each child of an affected individual has a 50% risk of inheriting the pathogenic variant. Approximately 10% of affected individuals develop MEN1 due to a de novo pathogenic variant in the MEN1 gene that occurs during early embryonic development.

The clinical diagnosis of MEN1 is established by published consensus criteria. (2012) define the diagnosis as either two or more MEN1-associated endocrine tumours, or one such tumour in combination with a first-degree relative with a clinical MEN1 diagnosis. Meeting these criteria constitutes the clinical diagnosis. The individual MEN1-associated tumours are themselves identified by their characteristic biochemical and imaging findings. Identification of a heterozygous pathogenic MEN1 variant by molecular genetic testing confirms the clinical diagnosis.

Main differential diagnoses include:

• : mild hypercalcaemia with reduced urinary calcium excretion, distinguished biochemically and by molecular testing; CASR, GNA11, AP2S1
• : clinically overlaps MEN1 but is typically milder and later in onset; CDKN1B
• : medullary thyroid carcinoma and phaeochromocytoma, with milder and often asymptomatic PHPT; RET
• : earlier-onset, predominantly GH-secreting tumours without MEN1-typical endocrinopathies; AIP

• Genetic testing supports establishing the diagnosis by identifying the underlying pathogenic variant, clarifying the genetic aetiology and providing a basis for genetic counselling.
• A confirmed result supports condition-specific surveillance and management options, which the treating physicians decide together with the affected individual.
• A known familial variant supports predictive testing of at-risk relatives, so they can clarify their personal risk and access surveillance and counselling where indicated.

• Giusti F, Marini F, Brandi ML. Multiple endocrine neoplasia type 1. 2005 Aug 31 [updated 2022 Mar 10]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: PMID:20301710.
• Halperin R, Tirosh A. Progress report on multiple endocrine neoplasia type 1. Fam Cancer. 2025;24(1):15. doi:10.1007/s10689-025-00440-4. PMID:.
• Thakker RV, Newey PJ, Walls GV, Bilezikian J, Dralle H, Ebeling PR, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990-3011. doi:10.1210/jc.2012-1230. PMID:.