What is Multiple Endocrine Neoplasia Type 2?

Multiple endocrine neoplasia type 2 (also known as MEN2) is a hereditary condition (condition passed down through families) that increases the likelihood of tumors in the hormone-secreting endocrine system (system of glands and organs that make and release hormones), particularly in the thyroid, parathyroid and adrenal glands.

The following conditions are caused by MEN2:

  • Medullary thyroid cancer (MTC), a type of cancer that affects the thyroid gland
  • Pheochromocytomas (tumors in the adrenal glands, small glands on top of the kidneys that make stress hormones)
  • Hyperparathyroidism (tumors in the parathyroid glands)
  • Other abnormal growths in the endocrine system, musculoskeletal tissues (involving the skeleton and muscles) and gastrointestinal tissues (involving the digestive system, such as the intestines)

What Are the Different Types of Multiple Endocrine Neoplasia Type 2?

MEN2 is classified into 3 subtypes:

  • MEN2A is the most common type of MEN2. People with this subtype have a higher risk of developing MTC, pheochromocytoma and primary hyperparathyroidism (PHPT). A pheochromocytoma is tumor on one or both adrenal glands. PHPT causes the parathyroid glands (small glands on top of the thyroid gland, a small, butterfly-shaped gland on the front of the neck) to secrete (release) too much parathyroid hormone. This can lead to increased calcium levels. These tumors can develop in childhood but are more likely to develop in adults.
  • Familial medullary thyroid cancer (FMTC) is considered a slightly different type of MEN2A. This condition is associated with an increased risk of developing MTC, but not pheochromocytomas or hyperparathyroidism. MTC usually develops between early and middle adulthood.
  • MEN2B is rarer than MEN2A, but typically occurs during infancy or early childhood as opposed to adulthood. All children with this condition develop MTC during their life. Around half develop pheochromocytomas. People with MEN2B have a higher risk of developing ganglioneuromas (tumors made of nerve and ganglion cells) and mucosal neuromas (benign, or not harmful, growths on the lips and tongue).

Doctors can determine the type of MEN2 your child has based on genetic testing, tumor type and how long the disease has been active.

What Causes Multiple Endocrine Neoplasia Type 2?

MEN2 is the result of a mutation (change) in the RET gene. These mutations can be inherited or occur at random as a new mutation. This is called a sporadic mutation. MEN2A is typically an inherited disease. In about half of children who have MEN2B, the condition is a consequence of a sporadic mutation.

What Are the Symptoms of Multiple Endocrine Neoplasia Type 2 and Its Associated Disorders?

The age at which children start to develop MEN2-associated tumors depends on the specific genetic mutation in the RET gene. The symptoms depend on the specific tumor your child develops.

MTC:

People with MTC sometimes do not have obvious symptoms. Potential symptoms include:

  • A tumor of the thyroid gland that may be detected during a physical exam or thyroid ultrasound
  • A lump in the front of the neck
  • Difficulty speaking normally
  • Difficulty swallowing
  • Difficulty breathing
  • Large lymph nodes
  • Throat and neck pain.

Hyperparathyroidism:

  • Weakness or fatigue
  • Depression
  • Confusion or forgetfulness
  • An increase in thirst and urination
  • Nausea
  • Lack of appetite
  • Abdominal pain
  • Constipation
  • Bone and joint pain
  • Osteoporosis (fragile bones)
  • An increased risk of developing kidney stones

Pheochromocytoma:

Some of these symptoms occur intermittently (every so often):

  • Headaches
  • Sweating
  • Pallor (pale skin) or flushing
  • Heart palpitations (very fast heartbeat or feeling like the heart may skip a beat)
  • Nausea
  • Lower chest or upper abdominal (belly area) pain
  • Weakness
  • Anxiety
  • High blood pressure
  • Weight loss
  • Tremors

Other MEN2A Symptoms:

  • Cutaneous lichen amyloidosis. People with MEN2A are also at risk for developing this condition in which itchy areas develop between the shoulder blades
  • Hirschsprung’s disease, a disorder in the intestines that causes constipation in infants

MEN2B Symptoms:

The symptoms of MEN2B vary, based on your child’s age:

Infants:

  • Constipation
  • Decreased muscle tone
  • Alacrima (an inability to produce tears)

School-Aged Children:

  • Long, thin face
  • Thin body
  • Mucosal neuromas (nodules on the libs or inside the mouth)
  • Eyelid eversion (eyelids that look inside out)
  • Constipation
  • Thyroid nodules
  • Scoliosis (curvature of the spine)
  • Early-onset MTC, usually before the child turns one. All children with MEN2B develop early-onset MTC. Children with early-onset MTC also have a higher risk of developing tumors, such as ganglioneuromas (in the intestinal tract)