4th April 2024

Multiple endocrine neoplasia types 1 & 2

Introduction

Multiple endocrine neoplasia (MEN) is a group of rare autosomal dominant inherited tumour disorders that manifest with specific organ dysfunction. MEN-1 is caused by a mutation of the MEN1 gene and MEN-2 by a mutation of the RET proto-oncogene. 

MEN-1

Background

Primary hyperparathyroidism is present in approximately 90% of patients. 40 to 70% of patients have functioning or non-functioning pancreatic neuroendocrine tumours, which include insulinomas, gastrinomas, VIPomas, and somatostatinomas. Pituitary adenomas are present in 30 to 40% of MEN-1 patients.

Patients, therefore, may present with symptoms of hyperparathyroidism and of a pituitary adenoma. Hyperparathyroidism leads to hypercalcaemia manifesting as ‘bones, stones and groans’. These symptoms are the most common presenting feature. Those with pituitary adenomas may have symptoms of hyperprolactinaemia (erectile dysfunction, infertility, galactorrhoea, headaches), acromegaly, hyperthyroidism and hypercortisolism. Pituitary adenomas cause both visual and endocrinologic symptoms. Patients may experience gradual vision loss, hyperprolactinaemia (erectile dysfunction, infertility, galactorrhoea, headaches), acromegaly, hyperthyroidism and hypercortisolism.

Diagnosis

The criteria for diagnosis involve any one of the following:

• Two or more MEN-1 associated endocrine tumours 
• One or more MEN-1 associated tumours and a first degree relative with MEN-1
• MEN1 mutation

Treatment

Treatment is focused on medical management of the manifestations of MEN and consideration of surgical removal of tumours.

MEN-2

Background

MEN-2 is extremely rare. MEN-2a and 2b both are associated with a high risk for early onset medullary thyroid carcinoma and phaeochromocytomas. Phaeochromocytomas can be screened with serum free metanephrines and normetanephrines. MEN-2a, in addition, has an increased association with parathyroid adenomas or hyperplasia.

Diagnosis

• MEN2A is diagnosed clinically by 2 or more specific endocrine tumours
• MEN2b is diagnosed clinically with medullary thyroid carcinoma < 40 years old, mucosal neuromas and a marfanoid habitus 
• If clinical features are inconclusive, RET genetic testing can be used

Treatment

Treatment for medullary thyroid carcinoma is thyroidectomy and lymph node dissection. However, patients with the RET gene may be offered a prophylactic thyroidectomy and then follow up calcitonin levels. Calcitonin is released by C cells of the thyroid and it opposes the action of PTH. Phaeochromocytomas are removed by adrenalectomy.

The table below summarises the features of the main types of MEN: