MEN 1 syndrome

• Autosomally dominant inherited mutation in the MEN1 gene which encodes the menin protein– located on chromosome 11.
  • Tumour suppressor gene
• Causes:
  • Pituitary adenomas
  • Parathyroid adenomas
  • Pancreatic tumours

Hyperparathyroidism

• Usually multiglandular disease.
• Usually the first manifestation of MEN1
• 40% of patients develop disease by 20 years old. 100% by 50 years old.
• Patients with MEN1 associated hyperparathyroidism are more likely to be younger, have 4 gland disease, and have a higher recurrence rate after subtotal parathyroidectomy.
• Patients need a full neck exploration with a sub-total parathyroidectomy and a thymectomy.
• If they can’t under go surgery – need bisphosphonates and calcimimetic drugs.

Pituitary adenomas

• 50% of patients with MEN1 will develop a pituitary adenoma
• Most are prolactinoma’s – 50%
• Can also get growth hormone secreting, ACTH secreting, and non-functioning tumours.
• To screen for pituitary tumours - do a prolactin level, serum IGF-1 (screens for acromegaly), early morning cortisol, TFTs, and LH/FSH levels.

Pancreatic neuroendocrine neoplasms

• 80% will be non-functional - 50% likelihood of malignancy.
• The most common functional tumour is a Gastrinoma - Gastrinomas are likely to be malignant.
• Rarely they can get Insulinoma’s
  • If tumours are < 1cm – usually monitored/surveilled.
  • Once > 2cm in size – managed with resection.
• Pancreatic tumours are what these patients have the most morbidity and mortality from

Other tumours in MEN1

• Foregut carcinoids – including tumours in the thymus and bronchus.
• Can also get angiofibromas, collagenomas, and lipomas (all cutaneous manifestations)
• Can also get adreno-corticoid tumours but these are usually benign and non-functional.

Indications for testing

• Family history
  • Germline testing should be offered to the relatives of a patient with MEN1
• Clinical
  • Young patient presenting with 4 gland hyperplasia
  • Young patient with multi-focal pancreatic NET
  • Patients presenting with 2 manifestations of MEN1

Screening

• Should be offered a program of clinical, biochemical and radiological screening
• Parathyroid
  • Annual plasma Ca and PTH
• Pancreatic NET
  • Annual gastrin, glucagon, VIP, Chromogranin A, insulin levels, and BSL.
  • There hasn’t been an optimal radiological program determined – institution dependent
  • It would be reasonable to perform a CT or MRI pancreas every 1-2 years.
• Pituitary screening
  • Annual plasma prolactin, IGF-1 levels, Pituitary MRI every 3-5 years.