Multiple endocrine neoplasia (MEN)

People with MEN1 develop tumors or excessive growth of two or more endocrine glands. These tumors are typically benign (noncancerous). The most frequently affected glands are:

• Parathyroid gland: Almost all people with MEN1 develop parathyroid tumors. These tumors cause the gland to produce too much parathyroid hormone, which often raises blood calcium levels.
• Pancreas: Many people with MEN1 develop pancreatic neuroendocrine tumors. These tumors affect the islet cells of the pancreas. Pancreatic NETs often cause production of too much stomach acid, which may lead to ulcers. Approximately 1 in 3 pancreatic NETs are cancerous.
• Pituitary gland: Some people with MEN1 also develop tumors on the pituitary gland. These tumors can cause the gland to produce too much of a few different hormones, including prolactin, growth hormone or corticotropin.

Less frequently, MEN1 may cause adrenal gland tumors, thyroid gland tumors or neuroendocrine tumors (NETs) in other organs. People assigned female at birth with MEN1 are also at increased risk of developing breast cancer.

MEN2 has two subtypes: MEN2A and MEN2B (formerly called MEN3).

Multiple endocrine neoplasia type 2A

Approximately 95 percent of people with MEN2 have the MEN2A subtype. MEN2A typically affects these glands:

• Thyroid: At least 90 percent of people with MEN2A develop medullary thyroid cancer at some point.
• Adrenal: About half of people with MEN2A develop pheochromocytoma, a type of adrenal tumor.
• Parathyroid: Less than 25 percent of people with MEN2A have parathyroid involvement. When MEN2A affects the parathyroid, it may cause hyperplasia (increased gland size) or a noncancerous tumor called parathyroid adenoma.

People with this subtype may also experience an itchy skin condition called cutaneous lichen amyloidosis. A small number of people with MEN2A may have a congenital condition called Hirschsprung's disease, which affects the nerves of the large intestine.

Multiple endocrine neoplasia type 2B

This rare subtype affects approximately 5 percent of people with MEN2. People with MEN2B may experience:

• Medullary thyroid cancer: At least 98 percent of people with MEN2B develop this type of tumor. Medullary thyroid cancer develops much earlier in people with MEN2B, typically in childhood or early adulthood.
• Pheochromocytoma: About 50 percent of people with MEN2B develop this type of adrenal tumor. Pheochromocytomas typically aren't cancerous, but they can cause other problems such as high blood pressure.
• Mucosal neuromas: Approximately 95 percent of people with MEN2B have this type of benign nerve tumor. Mucosal neuromas may develop on the tongue, lips, eyes or gastrointestinal tract. GI nerve tumors frequently cause digestive problems.
• Skeletal anomalies: Many people with MEN2B develop bone, joint or muscle problems. They may also have physical features such as a curved spine, long limbs and loose joints.
• Skin and eye changes: People with MEN2B may have thicker eyelids and lips. They may develop lumps or bumps on the lips, eyelids or tongue. Some people may not produce tears when they cry.

The most common sign of MEN1 and MEN4 is hyperparathyroidism (overactive parathyroid). Symptoms of hyperparathyroidism include:

• Bone symptoms, including pain, tenderness or bone thinning.
• Cognitive changes, such as depression or forgetfulness.
• Feeling ill, including fatigue or weakness.
• Gastrointestinal symptoms, such as nausea or vomiting.
• Urinary symptoms, including increased urinary frequency, higher amount of urine or kidney stones.

The most common sign of MEN2 is medullary thyroid cancer. Symptoms include:

• Difficulty swallowing
• Hoarse voice
• Lump in the neck or throat
• Neck pain
• Persistent cough
• Shortness of breath

Excessive gland growth or tumors may occur at different times. Regular imaging and blood testing allow us to identify and quickly treat any new developments in your condition. Early treatment gives you the best chance for a positive outcome.

In addition to routine monitoring, doctors may recommend active surveillance for some early-stage tumors. With this approach, stable tumors that do not progress may not require surgery. Doctors carefully monitor these tumors to look for any changes and recommend surgery if the tumor continues to grow.

The risk of developing medullary thyroid cancer is nearly 100 percent for people with MEN2A and MEN2B. Medullary thyroid cancer is aggressive and difficult to treat. Doctors typically recommend removing the thyroid (thyroidectomy) for people with these variants before any signs of cancer occur.

If your thyroid is removed, you will need to take thyroid hormone replacement medication for the rest of your life.

When possible, doctors often recommend surgery to remove tumors in the adrenal, parathyroid or thyroid glands. Some people may need medication to stabilize hormone levels before surgery.

With pancreatic neuroendocrine tumors in early stages, doctors may recommend active surveillance to avoid surgery if possible.

Enlarged and overactive glands without tumors can often be treated with medication. Pituitary tumors may also respond well to medication.

Medication can counter the excess hormones produced by overactive glands to balance hormone levels. Sometimes, medication may help before or after surgery to remove a tumor.

As a leading research center, Penn is always exploring new and innovative treatment options. We have one of the largest MEN clinical trials programs in the country. We use clinical trials to evaluate new potential treatments. When you receive care at Penn, you can access advance treatments not available elsewhere.

One example is our clinical trial of using CAR-T cell therapy to treat medullary thyroid cancer. Penn cancer experts designed a drug that targets receptors on medullary thyroid tumors.