Multiple Endocrine Neoplasia syndromes



Last Review Date: March 15, 2015


What is multiple endocrine neoplasia?

The multiple endocrine neoplasia (MEN) syndromes are a group of genetically inherited diseases that result in cancer or dysfunction in multiple organs. Cancer may arise in multiple organs at the same time, or a person may develop one cancer, then a second cancer in another organ, many years later. These cancers also often arise in younger people and may be more aggressive than ‘sporadic’ cancers – those that do not have a genetic inheritance pattern.

These syndromes can be divided into two groups, MEN-1 and MEN-2

MEN-1

This syndrome affects about 2 - 20 in every 100,000 people and is caused by a heritable defect in the MEN-1 tumour suppressor gene. If one of your parents has this syndrome, you have a 50 per cent chance of having the syndrome yourself. The syndrome most commonly affects the parathyroid gland (four small glands on the front of your thyroid), pancreas and pituitary gland (a small gland at the base of your brain). However, a patient with MEN-1 may also develop cancer of the small intestines, adrenal glands and lipomas (fatty lumps on your skin).

MEN-2

MEN-2 can be further subdivided into type 2A and type 2B. In type 2A people develop medullary thyroid cancer (MTC), phaeochromocytoma and an over-active parathyroid gland. Type 2B is characterised by MTC, phaeochromocytoma and cancer on the lips or tongue. In this syndrome there is a genetic mutation in the 'RET proto-oncogene' (see RET gene mutation testing in Tests).


Signs and symptoms

MEN-1

Someone who has MEN-1 syndrome is often asymptomatic. However, the first health problems people often notice are due to dysfunction of the parathyroid gland. By the age of 40, most will have abnormally high levels of calcium in their blood and this can lead to kidney stones, osteoporosis or muscle aches and pains. They may also notice symptoms caused by cancers in other organs. This may include an upset stomach, due to increased acid secretion, and low blood sugar levels. 

MEN-2

The most common presentation of this syndrome is a lump at the front of the neck that could be a sign of medullary thyroid cancer. Some people may first notice a racing heart or palpitations, sweating and anxiety. These symptoms are related to the development of a phaeochromocytoma. Finally, some people may notice changes or growths on their tongue or lips.


Tests

The choice of tests ordered by a doctor may vary depending on how the problem first comes to be recognised. They may include:

Laboratory tests

MEN-1

  • Calcium levels
    Calcium levels will often be raised in someone who has cancer in their parathyroid. Deranged levels of parathyroid hormone cause this increase.
  • Parathyroid hormone levels
    A cancerous parathyroid gland will often produce an increased amount of parathyroid hormone.
  • Renal (kidney) function tests
    An increase in blood levels of calcium may lead to deposition of calcium in the kidney and subsequent damage. At the time of diagnosis, it may be important to rule out any kidney damage or stones.
  • Insulin and C-peptide
    Measuring levels of insulin and C-peptide can test for a cancer that arises in the pancreas.
  • Prolactin and growth hormone levels
    Some cancers in MEN-1 may arise in a small gland just below the brain – the pituitary gland. This can be detected by measuring prolactin and growth hormone levels.
  • MEN1 gene mutation testing
    The MEN1 gene codes for a protein called menin. If both copies of the MEN1 gene are faulty not enough protein is produced and cells in some endocrine organs divide and proliferate uncontrollably leading to tumour development. More than 1000 different mutations have been found in the MEN1 gene in patients with MEN-1. DNA testing, which can detect most of these mutations, is available in Australia, however this testing is not covered by Medicare. 

MEN-2

  • Fine needle aspiration
    When someone has a lump in the neck, a sample is taken in a procedure that uses a fine needle and is guided by ultrasound. The small amount of tissue can give an indication of whether or not the lump is cancer.
  • Urine and plasma metanephrine
    If someone develops a cancer within their adrenal gland they will often produce elevated levels of chemicals such as metanephrine. High urine and plasma levels of these chemicals are used to diagnose phaeochromocytoma.
  • Serum calcitonin levels
    Calcitonin is produced by the c-cells in the thyroid gland. In cases of medullary thyroid cancer it will often be raised. Calcitonin levels, as well as a calcitonin stimulation test may be ordered to confirm MTC.
  • Thyroid function tests
    These are one of the first tests ordered when a doctor suspects a problem with your thyroid. It includes TSH, FT4 and FT3 and provides information about how your thyroid in functioning.
  • RET gene mutation testing
    The RET proto-oncogene codes for a signalling protein called RET that spans the cell membrane in various types of cells. There are more than 25 known mutations that cause this protein to become overactive and send signals into the cell promoting uncontrolled cell growth even when it has no signalling molecule bound to its outside region. DNA testing to detect these known mutations is available in Australia and is covered by Medicare in patients with a suspected diagnosis of multiple endocrine neoplasia type 2.
Non-laboratory tests
  • MRI and CT scan
    Imaging of the abdomen may be used to look for other cancers at the time of diagnosis.
  • Ultrasound
    People with MEN-2 often develop a lump in the neck and this can be investigated with the use of ultrasound. This imaging technique allows doctors to assess the location and characteristics of the lump and to help guide them in taking a sample for the lab to assess. 
 

It is important to note that due to the complex nature of these syndromes, the tests ordered by your doctor may vary from those listed above.


Treatment

This will vary depending on which organs are affected and the stage of the disease. It may involve both surgical and medical treatment.

  • Surgery – Some cancers may be removed from places like the thyroid and parathyroid glands as well as the adrenal glands
  • Medical treatment – In some cases surgery is not warranted and the doctor may advise taking medication rather than having a gland removed.

Related pages

On this site

Tests: calcium, calcitonin, metanephrines, prolactin, parathyroid hormone, growth hormone, thyroid function tests, insulin, C-peptide, eGFR

Conditions: Osteoporosis, medullary thyroid cancer

Inside the lab: Genetic testing

Elsewhere on the web

Medline Plus – MEN type 1
Medline Plus – MEN type 2
National Library of Medicine – Genetics: MEN
Medscape Reference – MEN 1
Medscape Reference – MEN 2


References


Fauci, Braunwald, Kasper et al. Harrison’s Principles of Internal Medicine 17th Ed. Mcgraw Hill, USA: 2360-63

Tuttle R. Clinical manifestations, diagnosis, evaluation, and staging of medullary thyroid cancer. (internet)Up to date (updated august 2012) Available at: http://www.uptodate.com.ezproxy.library.uq.edu.au/contents/clinical-manifestations-diagnosis-evaluation-and-staging-of-medullary-thyroid-cancer?

Kumar V, Abbas A, Fausto N, Aster J. Robins and Cotran’s Pathological Basis of Disease 8th Ed. Philadelphia, USA: Saunders Elsevier; 2010. Ch 24