What is it?
- Multiple endocrine neoplasia type 1 (MEN1) syndrome, or Wermer's syndrome, was first described in 1954 by US physician Dr Paul Wermer. It is an uncommon (1:30,000) inherited disease that affects men and women equally. Those who inherit the gene for MEN1 have an increased chance of developing overactivity, and enlargement and neoplasia of the parathyroid glands, the pancreas and the pituitary.
- The abnormality is on the long arm of chromosome 11. It is autosomal dominant with a high degree of penetrance.
How does it present?
- Presentation in 80% of cases is with parathyroid hyperplasia, adenomata and hyperparathyroidism. Patients develop asymptomatic hypercalcaemia on biochemical screening, or may have sporadic hyperparathyroidism.
- Pancreatic endocrine tumours occur in about 70%, usually between 15 and 50 years of age. Most are gastrinomas that cause Zollinger-Ellison syndrome. Peptic ulcers and oesophagitis are responsible for most of the morbidity and mortality. About 30% are insulinomas. Non-functioning tumours are fairly common.
- With both parathyroid and pancreatic disease there is diffuse hyperplasia and the pancreas usually has small multiple adenomata.
- Screening detects pituitary adenomas in 30% of patients. There is no diffuse hyperplasia, but prolactinomas are most common, causing hyperprolactinaemia. High levels of growth hormone produce acromegaly in about 30% of cases.
- Cushing's syndrome may occur due to excess adrenocorticotropic hormone. Other functioning tumours are rare.
- Subtle changes in the skin occur in as many as 90% of cases. There may be lipomas, collagenomas and multiple angiofibromas.
Making the diagnosis
- MEN1 should be considered in a patient with features of hyperparathyroidism or increased gastric acid production. If another family member is affected, screening may detect undiagnosed cases.
- Screening of firstand second-degree relatives can detect parathyroid, pancreatic or pituitary lesions. Early detection helps in morbidity, but does not seem to affect mortality. Screening should include checking serum calcium, fasting gastrin and prolactin.
Managing MEN1
- Drug treatment includes diazoxide to inhibit insulin release, PPIs in high dosage for gastrin-secreting tumours, and pituitary hormone replacement after surgery.
- Surgical treatment includes parathyroidectomy, but there is a high rate of recurrence. Pituitary tumours are treated by transsphenoidal excision. Surgery for pancreatic tumours is controversial and varies from complete excision of the pancreas and duodenum to removal of large lesions.
- Genetic counselling is needed.
- The prognosis for parathyroid and pituitary tumours is good, and pancreatic tumours are less malignant than sporadic tumours, with median survival of 15 years (only five years for sporadic tumours).
- Dr Barnard is a former GP in Fareham, Hampshire
