What are the other Names for this Condition? (Also known as/Synonyms)

• MEN 1 Syndrome
• MEN Syndrome Type 1
• Wermer's Syndrome

What is Multiple Endocrine Neoplasia (MEN) Type 1? (Definition/Background Information)

• Multiple Endocrine Neoplasia Type 1 (MEN Type 1) is an inherited disorder of the endocrine glands
• The disorder occurs in individuals, who are genetically predisposed to the condition, where the endocrine glands grow tumors, become overactive, release excess hormones, causing a set of symptoms and medical complications
• The endocrine glands involved in MEN Type 1 syndrome are the parathyroid, pancreas, and the pituitary glands

Parathyroid:

• The parathyroid gland consists of 4 small glands that are situated behind the thyroid gland in the neck
• The gland secretes a hormone, called parathyroid hormone (PTH), which is responsible for calcium metabolism in the body
• In MEN Syndrome Type 1, the parathyroid gland produces excess amounts of hormones, which results in high calcium levels in blood and urine, causing a thinning of the bones
• The bones become weak and are consequently prone to fractures
• High calcium levels in blood, causes an increased excretion of calcium through the kidneys, leading to kidney stone formation and kidney damage

Pancreas:

• The pancreas is a gland that is located behind the stomach in the abdomen
• It has a dual role - as an exocrine gland secreting digestive juices into the intestines, and as an endocrine gland secreting hormones. These hormones include:
  • Insulin - lowers blood sugar
  • Glucagon - increases blood sugar
  • Somatostatin - an inhibitory hormone
  • Gastrin - stimulates acid production in the stomach
  • Vasoactive intestinal peptide - secretes water into the intestine
• The common hormone involved in MEN Type 1 disorder is gastrin. Numerous gastrin-producing tumors cause an increased production of acids in the stomach
• This excess acid causes multiple gastric and duodenal (in the first part of the small intestine) ulcers; sometimes, even jejunal ulcers (second part of the small intestine) are observed
• Gastrin-producing tumors may also be part of a disorder, called  Zollinger Ellison syndrome

Pituitary:

• The pituitary gland is a small gland located in the brain. The hormones produced by this gland controls most of the basic body functions
• The pituitary gland secretes various hormones, which include:
  • Thyroid stimulating hormone (TSH) - that stimulates the thyroid gland to produce thyroid hormones
  • Adrenocorticotropic hormone (ACTH) - that stimulates the adrenal glands to produce corticosteroids
  • Prolactin - that regulates milk production, influences fertility and bone strength
  • Growth hormone (GH) - regulates body growth
  • Luteinizing hormone (LH) - regulates the production of sex hormones
  • Follicle stimulating hormone (FSH) - regulates fertility in men and women
• The commonly involved hormone in MEN Type 1 disorder is prolactin, and tumors secreting prolactin are called prolactinomas
• This leads to excessive milk production, interferes with fertility in women, and reduces sex-drive in men
• If the tumor is big, it can compress the visual pathway in the brain, causing vision problems

Who gets Multiple Endocrine Neoplasia (MEN) Type 1? (Age and Sex Distribution)

• Multiple Endocrine Neoplasia Type 1 disorder commonly manifests around  the ages 20-50 years, in individuals who are genetically predisposed to it
• Both males and females are equally affected; no predilection towards any particular sex has been observed

What are the Risk Factors for Multiple Endocrine Neoplasia (MEN) Type 1? (Predisposing Factors)

• The only risk factor for Multiple Endocrine Neoplasia Type 1 is individuals with a positive family history of the condition. MEN Type 1 is a genetic disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Multiple Endocrine Neoplasia (MEN) Type 1? (Etiology)

• Multiple Endocrine Neoplasia Type 1 disorders are genetically inherited
• It is inherited in an autosomal dominant pattern, which means any parent with the abnormal gene can pass it on to their children - a single copy of the gene is sufficient to transmit the condition to the offspring

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children who do not inherit the abnormal gene will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Multiple Endocrine Neoplasia (MEN) Type 1?

The signs and symptoms of Multiple Endocrine Neoplasia Type 1 disorder are classified according to the endocrine gland affected.

Symptoms due to excessive parathyroid hormone production include:

• Tiredness, weakness
• Muscle or bone pain
• Nausea and vomiting
• Indigestion, constipation
• Recurrent fractures due to thinning of bone
• Kidney stone formation leading to back pain, blood in urine

Symptoms from pancreatic gland over-activity:

• Abdominal pain
• Bloated feeling after meals, loss of appetite
• Black tarry stools (melena), due to gastric ulcer bleeding
• Burning sensation, aching in the upper abdomen or lower chest, which is relieved by antacids, milk, or food
• Nausea and vomiting
• Unintentional weight loss

Symptoms from pituitary gland over-activity:

• Headaches, vision problems
• Irregular or absence of menstrual periods
• Infertility in women
• Excessive milk production from the breast
• Lack of sexual desire
• Loss of hair in men (body and/or face)

How is Multiple Endocrine Neoplasia (MEN) Type 1 Diagnosed?

Depending on the signs and symptoms noted, a positive medical history (of Multiple Endocrine Neoplasia Type 1 syndrome), and physical examination, the physician may order a variety of tests that include:

• Serum calcium, phosphate, PTH, kidney function, prolactin, and a fasting gut hormone profile
• 24 hour urine calcium excretion
• CT abdomen or endoscopic ultrasound of pancreas
• MRI of the pituitary gland
• Ultrasound of the neck and Sestamibi scan (parathyroid scan)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Multiple Endocrine Neoplasia (MEN) Type 1?

The complications from Multiple Endocrine Neoplasia Type 1 disorder could include:

• Recurrent tumors
• Recurrent gastric and duodenal ulcers
• Pathological fractures, due to weak bones
• Kidney stones
• Vision disturbances

How is Multiple Endocrine Neoplasia (MEN) Type 1 Treated?

Treatment measures for Multiple Endocrine Neoplasia Type 1 include:

• A surgical removal of the affected gland is the treatment of choice
• Removal of all 4 parathyroid gland and a search for accessory glands
• The individual must be supplemented with daily calcium and vitamin D, in order to prevent low calcium levels in the body
• Prolactinoma (common benign pituitary tumor): This tumor can be effectively treated with cabergoline (dopamine agonists) and rarely requires surgery
• In case of pancreatic gland over-activity, there could be multiple small tumors in the pancreas and small intestine that could be producing gastrin and causing ulcers. It is very difficult to cure these tumor types through surgical removal. However, the symptoms due to excess acid production have been successfully treated in most cases, using strong antacids and proton pump inhibiting drugs, like omeprazole
• Some pancreatic tumors are amenable to surgical removal. Inoperable tumors that secrete hormones can be suppressed with octreotide analogue injections (inhibitory hormones)

How can Multiple Endocrine Neoplasia (MEN) Type 1 be Prevented?

• Currently there are no specific methods or guidelines to prevent Multiple Endocrine Neoplasia Type 1 genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for  treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Multiple Endocrine Neoplasia (MEN) Type 1? (Outcomes/Resolutions)

• In individuals with Multiple Endocrine Neoplasia Type 1, most of the parathyroid and pituitary tumors are benign
• Some pancreatic tumors may become malignant and spread to other organs causing severe medical complications. Death has been known to occur in some rare cases
• There is a need for lifelong regular scanning of the pituitary and pancreas glands, in order to screen for new tumors. Periodic monitoring for recurrent high calcium and gut hormones is also necessary

Additional and Relevant Useful Information for Multiple Endocrine Neoplasia (MEN) Type 1:

• As the term indicates, Multiple Endocrine Neoplasia (MEN) is a category of disorder that affects many endocrine glands. These glands produce several important body hormones
• MEN Type 1 and MEN Type 2 are subsets of the MEN disorder, with MEN Type 2, primarily affecting the thyroid gland

Thanks and Gratitude:

We sincerely acknowledge and thank Dr. Kamalakkannan Chokkalingam for reviewing the Multiple Endocrine Neoplasia Type 1 article. His valuable input and feedback has helped enrich the contents of this article.

Dr. K. Chokkalingam DM FRCP
Consultant Physician (Diabetes and Endocrinology)
Nottingham University Hospitals
Nottingham NG72UH, United Kingdom