What is multiple endocrine neoplasia?
Multiple endocrine neoplasia (MEN) is a group of rare, inherited conditions. It affects the endocrine system, which is made up of glands that produce hormones.
MEN can cause tumors and abnormal growths to form in several glands. These tumors can be noncancerous (benign) or cancerous. Some tumors may cause the body to make too many hormones, which can affect how the body works.
MEN can run in families. If a close family member has MEN, you may have a higher risk of developing it. Early diagnosis and regular checkups are important. At Penn Medicine, a team of specialists works together to diagnose and treat MEN. We offer genetic testing, routine screenings, and personalized cancer care to help find problems early and guide treatment over time.
Multiple endocrine neoplasia types
There are several types of multiple endocrine neoplasia. The most common are type 1 (MEN1) and type 2 (MEN2). Another type, MEN4, is rare.
People with MEN1 develop tumors or growths in two or more endocrine glands. Most of these tumors are noncancerous. The glands most often affected are:
- Parathyroid glands: Most people with MEN1 develop parathyroid tumors. These tumors cause the glands to make too much parathyroid hormone, which can raise calcium levels in the blood.
- Pancreas: Many people with MEN1 develop pancreatic neuroendocrine tumors (NETs). Some of these tumors make too many hormones, which can cause symptoms like stomach ulcers. Some pancreatic NETs are cancerous.
- Pituitary gland: Some people with MEN1 develop tumors in the pituitary gland. These tumors can cause the body to make too much of certain hormones, which may affect growth, fertility, or other body functions.
Less often, MEN1 affects the adrenal glands, thyroid gland, or other organs. People assigned female at birth with MEN1 also have a higher risk of breast cancer.
MEN2 has two subtypes: MEN2A and MEN2B.
Multiple endocrine neoplasia type 2A (MEN2A)
About 95 percent of people with MEN2 have the MEN2A subtype. In addition to affecting certain glands, MEN2A can also cause an itchy skin condition called cutaneous lichen amyloidosis. A small number of people may have Hirschsprung’s disease, which affects the nerves of the large intestine.
MEN2A most often affects these glands:
- Thyroid gland: People with MEN2A often develop medullary thyroid cancer during their lifetime.
- Adrenal glands: About half of people with MEN2A develop pheochromocytoma, a type of adrenal tumor that is usually noncancerous but can cause problems such as high blood pressure.
- Parathyroid glands: Some people with MEN2A develop enlarged glands or noncancerous parathyroid tumors.
Multiple endocrine neoplasia type 2B (MEN2B)
MEN2B is a rare subtype that affects about five percent of people with MEN2. People with MEN2B may develop:
- Medullary thyroid cancer: Nearly all people with MEN2B develop this cancer. It often starts in childhood or early adulthood.
- Pheochromocytoma: About half of people with MEN2B develop this tumor. It is usually not cancerous but can cause problems like high blood pressure.
- Mucosal neuromas: Most people with MEN2B develop these noncancerous nerve tumors. They can appear on the tongue, lips, eyes, or in the digestive tract.
- Bone and muscle changes: Many people with MEN2B have a curved spine, long limbs, or loose joints.
- Skin and eye changes: Some people with MEN2B may have thicker eyelids or lips and small bumps on the lips, eyelids, or tongue. They may also have dry eyes.
MEN4 causes symptoms similar to MEN1 but has a different genetic cause. People with MEN4 may develop tumors in the parathyroid glands, pituitary gland, or other glands that make hormones. It’s an uncommon type of multiple endocrine neoplasia.
Multiple endocrine neoplasia signs and symptoms
Symptoms vary depending on the type of MEN and where tumors form. Affected glands often produce too many hormones, which can lead to different symptoms.
The most common sign of MEN1 and MEN4 is hyperparathyroidism (overactive parathyroid). Symptoms may 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
What causes MEN?
MEN usually runs in families. It is caused by changes (mutations) in certain genes:
- MEN1: Changes in the MEN1 gene cause this type
- MEN2: Changes in the RET gene cause this type
- MEN4: Changes in the CDKN1B gene cause this type
Most people inherit a changed gene from a parent. Because of this, doctors often recommend screening for close family members of someone with MEN. However, up to 10 percent of people with MEN1 have a new gene change. This means they don’t have a family history of the condition.
Diagnosing multiple endocrine neoplasia
MEN can be hard to diagnose because tumors may not cause symptoms early on. At Penn Medicine, our specialists have extensive experience identifying and managing these tumors. Our diagnostic services include the Thyroid Nodule Clinic and programs focused on pancreatic cancer diagnosis and care. Your doctor will review your medical and family history, perform a physical exam, and recommend tests based on your symptoms and risk factors.
To confirm a diagnosis or better understand your condition, your care team may recommend blood and urine tests, genetic tests to look for gene changes that cause MEN, and imaging tests that help find tumors or abnormal glands.
Treatment for MEN
Treatment for multiple endocrine neoplasia may include monitoring, preventive care, surgery or medication. Treatment focuses on stabilizing hormones and removing tumors when possible.
Tumors and gland changes can develop over time. Regular imaging and blood tests help doctors find and treat problems early. Early treatment gives you the best chance for a positive outcome.
Doctors may also recommend active surveillance for some early-stage tumors. With this approach, small or stable tumors are closely monitored and may not need surgery right away.
Because people with MEN2A or MEN2B have a high risk of developing medullary thyroid cancer during their lifetime, doctors recommend removing the thyroid, called a thyroidectomy.
If your thyroid is removed, you’ll need lifelong thyroid hormone replacement therapy.
When possible, doctors may remove tumors from the adrenal, parathyroid, or thyroid glands. Some people need medication before surgery to control hormone levels.
For some early-stage pancreatic neuroendocrine tumors, doctors may delay surgery and use close monitoring instead.
Some conditions caused by MEN can be treated with medication. For example, medication may help control hormone levels from overactive glands or be used before or after surgery as part of your treatment plan.Some pituitary tumors may also respond well to medicine.
As a leading academic medical center, Penn Medicine is advancing new treatments for endocrine cancers and conditions like MEN. Our clinical trials focus on innovative therapies, including targeted treatments for neuroendocrine tumors and medullary thyroid cancer.
One example is research using CAR T cell therapy to treat medullary thyroid cancer. This approach is designed to target specific cells in the tumor.
Expert care for MEN diagnosis and treatment
MEN is a complex condition that requires coordinated care across multiple specialties. At Penn Medicine, experienced teams work together to provide diagnosis, treatment, and long-term management.
When you partner with us for MEN care, you have access to specialized programs, including:
- Neuroendocrine tumor program: Expert care for neuroendocrine tumors, with support services, education, and care coordination throughout your treatment.
- Pituitary center: A dedicated center offering specialized care for pituitary conditions, with a team that may include endocrinologists, neurosurgeons, radiation oncologists, and other specialists.
- Thyroid and parathyroid cancer program: Coordinated care from endocrinology, surgery, and oncology experts, with personalized treatment planning.
- Genetics services: Genetic testing and counseling to confirm diagnosis and identify risks for you and your family.
Our teams support people with MEN through every stage of care, including treatment, surgery when needed, and long-term follow-up care.
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