Multiple endocrine neoplasia type 2 is a rare genetic disorder that causes tumors in the thyroid, parathyroid, and adrenal glands.

Multiple endocrine neoplasia type 2 (MEN2) is one of several types of multiple endocrine neoplasia (MEN) along with MEN1 and MEN4. These three forms of the disease are associated with different genetic mutations passed through families.

Some of the conditions that people with MEN2 are at a high risk of developing include:

  • medullary thyroid cancer (MTC)
  • pheochromocytoma, a type of adrenal gland tumor
  • parathyroid disease

MEN2 can also be subdivided depending on its genetic features and the types of tumors that develop. For people with gene mutations that put them at a high risk of aggressive MTC, doctors often recommend the removal of the thyroid gland in childhood before cancer occurs.

In this article, we examine MEN2 in more detail subtypes, treatment options, and its outlook.

Multiple endocrine neoplasia type 2 vs. type 1

MEN is divided into MEN1, MEN2, and MEN4. Mutations in the MEN1 gene cause MEN1, while mutations in the RETgene cause MEN2. MEN4 is much rarer than these two forms but develops due to mutations in CDKN1B.

MEN1 occurs in roughly 1 in 30,000 people and puts you at risk of:

MEN2 occurs in roughly 1 in 35,000 people and increases your risk of:

  • MTC and C-cell hyperplasia, its precursor
  • pheochromocytoma adrenal gland tumors
  • tumors and enlargement of your parathyroid gland

MEN2 is a hereditary cancer syndrome caused by genes inherited from your parents. MEN2 is further subdivided into three types:

  • MEN2A: People with MEN2A have an increased risk of MTC, usually in early adulthood. They also have an increased risk of pheochromocytoma and parathyroid disease.
  • MEN2B: People with MEN2B have an increased risk of MTC, usually in early childhood. They also have an increased risk of pheochromocytoma and some other conditions like mucosal neuromas of the lips and tongue.
  • Familial medullary thyroid carcinoma (FMTC): People with FMTC have an increased risk of MTC, often in middle age. FMTC is sometimes considered a variant of MEN2A

MEN2A is the most common form, making up about 70% to 80% of cases. Some people can develop MEN2 without a family history due to sporadic genetic mutations.

Almost everybody with MEN2 develops MTC at some point, but lifetime rates of other associated tumors vary by subtype:

PhenotypeMedullary thyroid carcinomaPheochromocytomaParathyroid disease
MEN2A95%50%20% to 30%
FMTC100%less than 1%less than 1%
MEN2B100%50%less than 1%

Medullary thyroid carcinoma symptoms

Signs and symptoms of MTC can include a lump in your thyroid gland and swelling around the front of your neck. More advanced cases might also cause:

Pheochromocytoma symptoms

Pheochromocytomas cause your body to produce too much epinephrine and norepinephrine. They may or may not cause symptoms. Symptoms can occur as often as several times per day or as infrequently as a couple of times per month.

Associated signs and symptoms that may appear for sustained periods or brief moments include:

Parathyroid disease symptoms

Parathyroid disease often doesn’t cause symptoms in the early stages. Symptoms are often related to high calcium levels in your blood. They might include:

Some people with MEN2 only develop mild symptoms, while others may develop life threatening tumors. People with MEN2B, in particular, tend to develop thyroid tumors that spread quickly to other body parts.

Some people with MEN2 have other problems, such as:

  • cutaneous lichen amyloidosis, a rare skin condition that causes a patch of itchy, scaly and dark skin between your shoulders
  • Hirschsprung disease, a birth defect that causes gastrointestinal problems
  • a collection of skeletal problems called marfanoid habitus
  • spinal problems
  • joint laxity
  • mucosal neuromas, typically in the lips or tongue
  • intestinal ganglioneuromas

It’s important to tell your child’s doctor if you have a family history of MEN so that your child can be screened appropriately. It’s also important to visit your doctor if you develop any characteristic signs of MEN or any other genetic syndrome.

A doctor will likely recommend genetically testing your child early in life if you have a family history of MEN. They may also recommend genetic testing later in life if you develop characteristic features.

A MEN2 diagnosis is primarily made based on the finding of an associated RET gene mutation.

Children often need regular tests from around 5 years of age to look for signs of tumors. They may receive:

  • ultrasound
  • physical examination
  • blood tests to measure calcitonin

Prophylactic thyroidectomy, also called a risk-reducing thyroidectomy, is the treatment of choice for people with MEN2 since almost everybody develops MTC.

This procedure involves removing the thyroid gland before cancer develops. It’s often performed in the first month of life in children with MEN2B or around 5 years for children with high risk MEN2A.

Thyroidectomy may not be required for people with low risk mutations until late childhood or adulthood.

You’ll need lifelong thyroid hormone replacement therapy after having your thyroid removed.

The drugs vandetanib and cabozantinib are Food and Drug Administration (FDA)-approved for people with progressive metastatic MTC ineligible for surgery.

Other treatment

Pheochromocytoma is often treated with laparoscopic adrenalectomy to remove one or both adrenal glands.

High calcium levels may not require treatment until symptoms are unmanageable. You may receive a total or partial removal of the parathyroid glands or medications.

Part of your gland may be transplanted to a different part of your body, often your non-dominant forearm.

The outlook for MEN2 varies widely. MEN2B tends to lead to more aggressive tumors than MEN2A

MTC recurrence is common in people with MEN2B. Recurrence can occur up to 20 years after initial treatment. The overall survival is generally high, with a 2019 study reporting a 94% survival rate at 10 years among 66 people with MEN2-associated MTC identified between 1986 and 2017.

People with MEN2B who don’t receive a thyroidectomy have a high risk of metastatic MTC at an early age. About half of people in this group live fewer than 25 years.

MEN2 is caused by your genetics and isn’t preventable. Regular screening can help catch the condition in the early stages and prevent complications of tumors and associated conditions.

MEN2 is an inherited genetic condition that increases your risk of certain tumors like MTC, adrenal gland tumors, and parathyroid tumors. It’s divided into several subtypes depending on the features of the disease.

It’s important to speak with your child’s doctor if you have a family history of MEN2 so that your child can receive proper screening. The doctor will test your child for associated genes. If your child has these genes, they will need regular screening and may need surgery to remove their thyroid gland.