Definition and Overview

Multiple endocrine neoplasia (MEN) syndromes are rare, inherited disorders characterised by the development of abnormal growths in endocrine glands, namely the parathyroid, pituitary, thyroid, and adrenal glands as well as the pancreas. The condition can cause the glands to enlarge and become hormonally overactive, or produce more hormones than the body needs.

MEN syndromes occur in three patterns, namely types 1, 2A, and 2B. MEN type 1, which is also known as multiple endocrine adenomatosis and Wermer syndrome, results in the formation of tumours in the pituitary gland, islet cells of the pancreas, and parathyroid glands. Some patients also have tumours in other parts of the digestive tract as well as adrenal cortical and carcinoid tumours.

MEN1 sufferers experience a range of symptoms due to hormonal imbalance. Hormones released by different endocrine glands are responsible for controlling and instructing the functions of various organs. The overproduction of hormones results in different disorders, including hyperparathyroidism (caused by an overactive parathyroid glands), ulcers in the stomach and small intestine (caused by the overproduction of gastrin by islet cell tumors), and excessive growth of soft tissue (overproduction of growth hormone).

Based on statistics, MEN1 affects just one in every 30,000 people. It can affect both genders and can develop at any age. Currently, there is no cure for the condition but therapies are available for the treatment and management of symptoms and complications.

Causes of Condition

MEN1 is an inherited disorder, which means that it is passed from parents to their children. It is caused by a mutation in a gene also called MEN1, which increases a person’s risk of developing endocrine tumours and other MEN1 symptoms.

Every cell in the body has two copies of each gene; one is inherited from the father and the other one from the mother. The mutation only occurs in one copy of the gene, which means that a parent with a gene mutation has a 50% chance of passing along his or her mutated gene to his or her child. MEN1 develops when the normal gene that is inherited from the unaffected parent is lost or damaged during normal cell division.

A MEN1 sufferer who wishes to have children has an option to undergo a medical procedure called pre-implantation genetic diagnosis, which allows people with genetic mutations to prevent their children from inheriting their condition. For this procedure, several embryos are tested and those that do not have the mutation are transferred to the uterus through in vitro fertilisation (IVF).

Key Symptoms

Symptoms of MEN1 vary from person to person and depend on which glands are affected. These include:

  • Anxiety

  • Black, tarry stools

  • Bloated feeling after meals

  • Bone enlargement

  • Changes in vision

  • Constant headaches

  • Cushing’s syndrome, which is caused by pituitary tumours. Its symptoms include weight gain, fatty deposits in the midsection, skin injuries that are slow to heal, fatigue, and glucose intolerance, among others.

  • Discomfort in the lower chest or upper abdomen

  • Hair loss

  • Hyperparathyroidism, which causes muscle or bone pain, tiredness, and weakness, among others

  • Infertility

  • Lack of menstrual periods (in women)

  • Mental changes

  • Overproduction of breast milk

  • Problems with sexual function

Patients with pancreatic neuroendocrine tumours, which affects up to 60% of MEN1 sufferers, develop gastrinoma, which causes the overproduction of gastrin and acid in the stomach, resulting in stomach or duodenal ulcers. Also known as Zollinger-Ellison syndrome, this can cause severe bleeding, ulceration, and stricture of the upper gastrointestinal tract. 10% of patients with MEN1 also develop insulinoma, which causes the overproduction of insulin and results in low blood sugar level.

Who to See and Types of Treatments Available

A genetic testing for MEN1, which is conducted by a genetic counselor or doctor trained in genetics, is used to diagnose MEN1 in those showing symptoms mentioned above or test first-degree family members to see if they also have the condition. This is followed by blood tests that measure the levels of specific hormones as well as imaging tests to detect abnormal growths. These tests often include:

  • Computed tomography (CT) scan and/or magnetic resonance imaging (MRI) of the head and abdomen

  • Insulin test

  • Parathyroid biopsy

  • Serum adrenocorticotropic, follicle stimulating, luteinising, and parathyroid hormones level tests

  • Cortisol, calcium, gastrin, and glucagon level tests

  • Ultrasound of the neck

Treatment of MEN1 often involves the removal of part (partial resection) or the entire (complete resection) affected glands.

  • Hyperparathyroidism is managed by removing the parathyroid glands.

  • Pituitary tumours - Some small pituitary tumours can be adequately managed with dopamine agonists. However, larger tumours that cause vision problems are removed with surgery.

  • Pancreatic neuroendocrine tumours - Surgery is considered if the tumour is larger than 2cm. It could involve removing just a part of the pancreas, stomach, and duodenum. In severe cases, the whole pancreas may be removed.

Patients are then placed on life-long hormone replacement therapy in which they take medications to replace the hormones that their resected gland can no longer produce.

Aside from hormone replacement therapy, patients with benign tumours that have been removed with surgery typically no longer require further treatment. However, if tumours are found to be malignant or cancerous, gland resection is commonly followed by either chemotherapy or radiation therapy; both aim to destroy remaining cancer cells to prevent recurrence.

The prognosis for patients with malignant tumours is often not as good as those with benign growths. Their chance of survival depends on the stage of their cancer, whether or not cancer has spread to nearby or distant body parts, and how their body responds to treatment.

References:

  • Kronenberg HM. Polyglandular disorders. in: Goldman L, Ausiello D, eds. Cecil Medicine. 24th ed. Philadelphia, Pa: Saunders Elsevier; 2011: chap 239.

  • National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Neuroendocrine Tumors. National Comprehensive Cancer Network; 2011. Version 1.2011.

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