What Is Multiple Endocrine Neoplasia (MEN)?
Multiple endocrine neoplasia (MEN) syndromes are a group of rare inherited conditions that require specialized care. These syndromes can affect multiple organ systems and increase your risk of developing cancer.
At Penn Medicine, we have the experience and expertise needed to diagnose and treat these rare conditions. Accurate diagnosis and ongoing monitoring are critical for managing multiple endocrine neoplasia. Our collaborative approach ensures you receive the appropriate monitoring and timely treatments for all aspects of your condition.
Multiple endocrine neoplasia causes overgrowth or tumors on one or more endocrine glands. These glands are part of the endocrine system, which produces hormones to regulate certain body functions. Tumors and growths from MEN may be benign (noncancerous) or cancerous.
Multiple endocrine neoplasia runs in families, so having a family member with the condition increases your risk.
Multiple Endocrine Neoplasia Types
There are several types of multiple endocrine neoplasia. The two most common types are multiple endocrine neoplasia type 1 (MEN1) and multiple endocrine neoplasia type 2 (MEN2).
Multiple endocrine neoplasia type 4 (MEN4) is rare. This type has similar symptoms to MEN1 but has a different genetic cause.
Multiple Endocrine Neoplasia Type 1
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. Women with MEN1 are also at increased risk of developing breast cancer.
Multiple Endocrine Neoplasia Type 2
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.
What Causes Multiple Endocrine Neoplasia?
MEN typically runs in families. Different genetic mutations (changes) cause each type:
- MEN1: Mutations to this gene cause MEN1.
- RET: Mutations to this gene cause MEN2.
- CDKN1B: Mutations to this gene cause MEN4.
Usually, a person inherits a mutated gene for MEN from a parent. That’s why doctors recommend screening close relatives of anyone diagnosed with the condition. But up to 10 percent of people with MEN1 have a new mutation and do not have a family history of the condition.
Multiple Endocrine Neoplasia Signs and Symptoms
Symptoms vary widely depending on the type of MEN and tumor location. Often, the affected glands produce excess hormones. High levels of different hormones can cause a wide range of symptoms.
MEN1 and MEN4 Signs and Symptoms
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.
MEN2 Signs and Symptoms
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
Why Choose Penn Medicine for Multiple Endocrine Neoplasia Care?
All types of multiple endocrine neoplasia are rare and cause a wide variety of symptoms and related conditions. At the Abramson Cancer Center, our specialists have unparalleled experience diagnosing and treating MEN. As an academic medical center, we also conduct innovative research.
When you choose Penn for MEN care, you have access to specialized programs, including:
- Neuroendocrine Tumor Program: Our neuroendocrine specialists are recognized experts in the field. We provide leading-edge diagnostics and treatment options. Penn was one of the first programs to offer genetic testing for neuroendocrine tumors and we are researching new treatments. Explore the benefits of the Neuroendocrine Tumor Program.
- Pituitary Center: We have one of the few dedicated pituitary centers in the country. You receive innovative, comprehensive care from an expert team. Leading-edge treatment options include medication, minimally invasive surgery and radiation. Discover more about the Pituitary Center.
- Thyroid and Parathyroid Cancer Program: Experts from endocrinology, oncology and other departments work together to diagnose and treat these cancers. Doctors regularly meet to discuss the best treatment options for different tumor types. Find out more about the Thyroid and Parathyroid Cancer Program.
- Translational Medicine and Human Genetics: The genetic mutations that cause MEN are typically passed down from parent to child. Genetic testing can help confirm a diagnosis and put you on the path to active surveillance and preventive care. Learn more about the Translational Medicine and Human Genetics Program.
Diagnosing Multiple Endocrine Neoplasia
MEN can be difficult to diagnose because tumors may not cause symptoms in the early stages. At Penn, our specialists have decades of experience diagnosing and treating these tumors. Our specialized diagnostic services include the Thyroid Nodule Clinic and the Pancreatic Cancer Diagnosis program.
Doctors may suspect MEN if you have:
- Two or more tumors commonly associated with MEN
- One tumor associated with MEN and a family history of MEN
- The MEN1, RET or CDKN1B mutation, even if you don’t have any signs or symptoms of MEN
- Hyperparathyroidism
- Characteristic facial features of MEN2B
Diagnostic Testing
Your doctor will take a family history, perform a physical exam and order tests, which may include:
- Blood and urine tests: These tests measure levels of hormones and other substances in your body. Examples of hormone levels your doctor may test include cortisol, gastrin, insulin or parathyroid hormone. Elevated blood sugar or calcium may also indicate excess hormones connected to MEN.
- Genetic tests: These tests look for the specific mutations that cause MEN.
- Imaging: These tests help your doctor see a particular tumor or abnormal gland. Depending on the location, your doctor may request a computed tomography (CT) scan, magnetic resonance imaging (MRI) scan or ultrasound.
Multiple Endocrine Neoplasia Treatment
Treatment for multiple endocrine neoplasia may include monitoring, preventive care, surgery or medication. Treatment focuses on stabilizing hormones and removing tumors when possible.
Monitoring
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.
Preventive Care
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.
Surgical Treatment
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.
Medication
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.
Clinical Trials
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. Learn more about the CAR-T cell clinical trial.
Request an Appointment
To make an appointment, please call 800-789-7366 or request a callback.