Multiple Endocrine Neoplasia


  • Rare, autosomal dominant syndromes characterised by hyperplastic/neoplastic activity in multiple glands
  • Generally, MEN can be classified as
    • MEN 1 (Wermer’s syndrome) (inactivating mutations of MENIN- tumour suppressor gene; Ch 11)
    • MEN 2 (Sipple’s syndrome) (gain of function mutations of RET proto-oncogene; Ch 10
      • Primary Hyperparathyroidism
      • Medullary carcinoma of the thyroid (of C cell origin)
      • Phaeochromocytoma/adrenal hyperplasia
      • NB There may also be physical signs (MEN 2b)
        • Marfanoid; skeletal abnormalities, dental abnormalities, multiple mucosal neuromas


  • MEN 1
    • Cutaneous and mucosal tumours (90%) tend to present from teenage years onward.  If there is a family history, the diagnosis may already be known.  If not, diagnosis is often not made until 40s
    • Usually presents with symptoms of tumours/hyperplasia e.g.
      • Hypercalcaemia and stone disease (80%)
      • Zollinger-Ellison
        • Dyspepsia and peptic ulcers occur in around 10% and are a major source of mortality in patients with MEN 1
      • Hypoglycaemia
      • Amenorrhoea (hyperprolactinaemia) (30%)
        • Prolactinomas tend to be more aggressive in patients with MEN 1 than sporadic cases
      • Acromegaly
      • Mass effects of pituitary tumours
  • MEN 2
    • Most patients will present with medullary thyroid carcinoma and often present with a neck lump and hypercalcitoninaemia (hypercalcaemia)
    • Symptoms of phaeochromocytoma and hypercalcaemia may also present in the first instance
    • MEN 2A (Sipple’s syndrome)
      • Usually presents later (4th-5th decade); parathyroid hyperplasia is common but hypercalcaemia is uncommon (as is hyperparathyroidism)
    • MEN 2B
      • Tends to present earlier with mucosal neuromas and intestinal gangliomas (which may cause GI symptoms including failure to thrive)


  • In general, the management of MEN syndromes is surgical as hyperplasia/neoplasia arises
    • In MEN 2, thyroidectomy is usually performed prophylactically in childhood
    • In MEN 1, patients should be routinely screened for hypercalcaemia, GI hormones and imaging
      • (Pituitary and pancreas imaging in MEN1)
    • In MEN 2, screening should include calcium, urinary catecholamine/metabolites

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