Multiple Endocrine Neoplasia Type 1 (MEN1)

What are the tumours associated with MEN1?

MEN1 is typically characterised by tumours in the following locations of the body:

• Glands of the endocrine system (i.e., parathyroid, pituitary, pancreas)
• Other parts of the digestive tract (e.g., duodenum and stomach)

1. Parathyroid glands
About 95% of people with MEN1 develop tumours in the parathyroid glands by age 50.

These four pea-sized glands produce the parathyroid hormone, which helps to maintain the right balance of calcium and phosphate in your body. Over time, MEN1 can affect all four glands.

MEN1-related tumours cause the parathyroid glands to become overactive, producing too much parathyroid hormone. This condition, called hyperparathyroidism, is the most common complication associated with MEN1.

The parathyroid glands are located near the thyroid gland in the neck

Excess parathyroid hormone can cause calcium levels in your blood to rise too high. Complications may include:

• Fractures
• Kidney stones
• Muscle weakness
• Tiredness or confusion
• Increased thirst and urination
• Depression
• Aches and pains in bones and joints
• Constipation or abdominal pain

2. Pancreas and digestive tract
About 40% of people with MEN1 develop tumours in the pancreas, duodenum (small intestine), or other parts of the digestive tract.

Many different types of tumours may develop at the same time. Many of these tumours produce hormones while others do not. Some tumours may be cancerous.

In people with MEN1, the two most common tumours of the digestive tract are:

• Gastrinomas. These tumours produce the hormone gastrin, which causes the stomach to release acid that helps it digest food. Too much gastrin can cause stomach ulcers and severe diarrhoea. Over time, some of these tumours may become cancerous.
• Insulinomas. These tumours form in the pancreas, where the cells produce the hormone insulin. Insulinomas make too much insulin, leading to low blood sugar. These tumours are almost always noncancerous and can usually be removed with surgery.

Other rare pancreatic tumours include:

• Glucagonomas. These tumours produce too much of the hormone glucagon, which raises blood sugar levels.
• VIPomas. These tumours may produce too much of a hormone called vasoactive intestinal peptide (VIP), which may result in profuse watery diarrhoea.

3. Pituitary gland
Nearly one in three people with MEN1 develop tumours in the front part of the pituitary gland called the anterior lobe. Like other pituitary tumours, these growths are often small in size and are almost always noncancerous.

The pituitary gland sits at the base of the brain

In people with MEN1, the two most common pituitary tumours are:

• Prolactinomas. These tumours are the most common, and produce the hormone prolactin. Normally, this hormone signals women’s breasts to produce milk during pregnancy and breastfeeding. Women with a prolactinoma may notice milk discharge from their breast(s) (galactorrhea) when they are not pregnant or breastfeeding. In both men and women, high prolactin levels can lead to infertility and bone loss.

• Growth hormone (GH) tumours. These tumours are the second most common, and produce excess GH which causes bones and other vital organs to grow larger in size. This condition is called acromegaly. Health problems caused by excessive GH include hypertension, diabetes, heart disease, stroke, arthritis, carpal tunnel syndrome and tumours of the colon or rectum.
  
  Pituitary tumours that grow large in size may prevent the pituitary gland from making enough hormones, leading to a condition called hypopituitarism.
  
  The tumours may also press against nearby brain tissues such as the eye nerve, causing vision problems and headaches.
  
  Hypopituitarism can usually be treated with oral hormone replacement pills.

• Other tumours
  MEN1 can also cause tumours to develop in other parts of the body. Examples include:

  • Tumours in other endocrine glands. An example is the adrenal glands.
  • Carcinoid tumours. Slowgrowing tumours most often found in the stomach, thymus and lungs.
  • Skin tumours and tumours under the skin. Common ones include angiofibromas, lipomas (benign tumours made of fat cells), and collagenomas (tumours involving a protein in the skin called collagen).
  • Meningiomas and ependymomas. Tumours of cells that line the brain and spinal cord.