4th April 2024

MEN syndromes

Multiple endocrine neoplasia (MEN) syndromes are a rare group of disorders characterised by an inherited predisposition to benign or malignant neoplasms of the endocrine system with characteristic organ involvement. 

Pathophysiology 

MEN syndromes are a group of autosomal dominant disorders divided into ‘types’ by clinical characteristics. MEN1 affects 1-3 in 100,000 and is due to a defect in the MEN1 gene, whilst MEN2 has been reported in approximately 1000 families worldwide and is caused by a mutated RET proto-oncogene. Based on clinical characteristics, MEN2 can be further subdivided into MEN2A and MEN2B subtypes (see Table 1). Other genetic conditions affecting the parathyroid gland include pseudohypoparathyroidism. 

Table 1: characteristics of different MEN syndromes. 

*This is the most common presenting feature of individuals with MEN1.

Tumours form in distinctive organ systems and may be functioning or non-functioning; hypersecretion of hormones from functioning tumours leads to specific symptoms dependent on tumour type. Individuals with MEN1 can present with hypercalcaemia caused by hyperparathyroidism. 40-70% of patients with MEN1 have pancreatic neuroendocrine tumours; ranging from insulinomas, which present with hypoglycaemia, VIPomas causing severe, watery diarrhoea, to gastrinomas, (Zollinger-Ellison syndrome). Zollinger-Ellison syndrome is the most common cause of symptomatic disease in patients with pancreatic tumours.

Management

Early prophylactic thyroidectomy in patients diagnosed genetically with MEN2 in childhood may be indicated, given that most patients will ultimately develop MTC. Otherwise, treatment centres around surgical management of tumours and medical management of symptomatology. Routine monitoring of known carriers begins in childhood and should take place every few years to reduce associated morbidity and mortality.