Multiple Endocrine Neoplasia

Background/Epidemiology

• 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)
    • Primary Hyperparathyroidism
    • Pituitary tumours
    • Pancreatic neuro-endocrine tumours (e.g. insulinoma, gastrinoma) (70%)
  • 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

Presentation

• 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)

Management

• 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