Multiple Endocrine Neoplasia Syndromes in Children

What Are Multiple Endocrine Neoplasia Syndromes?

Multiple endocrine neoplasia (MEN) syndromes are inherited disorders that affect the endocrine system. The endocrine system is made up of glands and cells that make hormones and release them into the blood. MEN syndromes may cause hyperplasia (the growth of too many normal cells) or tumors that may be benign (not cancer) or malignant (cancer).

There are several types of MEN syndromes and each type may cause different conditions or cancers. Patients and family members with an increased risk of these syndromes should have genetic counseling and tests to check for the syndromes.

The two main types of MEN syndromes are MEN1 and MEN2.

What Are the Signs and Symptoms of MEN 1 Syndrome in Children?

MEN1 syndrome is also called Werner syndrome. This syndrome usually causes tumors in the parathyroid gland, pituitary gland, and pancreas. Rarely, it causes tumors in the adrenal glands, gastrointestinal tract, fibrous tissue, and fat cells. The tumors make extra hormones and cause certain signs or symptoms of disease. The signs and symptoms depend on the type of hormone made by the tumor. The most common sign of MEN1 syndrome is hypercalcemia. Hypercalcemia occurs when the parathyroid gland makes too much parathyroid hormone.

Signs and symptoms of hypercalcemia include the following:

A diagnosis of MEN1 syndrome is usually made when tumors are found in two different places. The prognosis (chance of recovery) is usually good.

Children who are diagnosed with MEN1 syndrome are checked for signs of cancer starting at age 5 and continuing for the rest of their life. Talk to your doctor about the tests and procedures that should be done to check for signs of cancer and how often they should be done.

Children with MEN1 syndrome may also have primary hyperparathyroidism. In primary hyperparathyroidism, one or more of the parathyroid glands makes too much parathyroid hormone. The most common sign of primary hyperparathyroidism is kidney stones. Children with primary hyperparathyroidism may have genetic testing to check for gene changes linked to MEN1 syndrome.


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What Are the Signs and Symptoms of MEN 2 Syndromes?

MEN2 syndrome includes three subgroups:

MEN2A syndrome

MEN2A syndrome is also called Sipple syndrome. A diagnosis of MEN2A syndrome may be made when the patient or the patient's parents, brothers, sisters, or children have two or more of the following:

  • Medullary thyroid cancer
  • Pheochromocytoma (a tumor of the adrenal gland)
  • Parathyroid gland disease (a benign tumor of the parathyroid gland or increase in the size of the parathyroid gland)

Signs and symptoms of medullary thyroid cancer may include:

  • A lump in the throat or neck
  • Trouble breathing
  • Trouble swallowing
  • Hoarseness

Signs and symptoms of pheochromocytoma may include:

  • Pain in the abdomen or chest
  • A strong, fast, or irregular heartbeat
  • Headache
  • Heavy sweating for no known reason
  • Dizziness
  • Feeling shaky
  • Being irritable or nervous

Signs and symptoms of parathyroid disease may include:

  • Hypercalcemia
  • Pain in the abdomen, side, or back that doesn't go away
  • Pain in the bones
  • A broken bone
  • A lump in the neck
  • Change in voice, such as hoarseness
  • Trouble swallowing

Family members of patients with the MEN2A syndrome should have genetic counseling and be tested in early childhood, before age 5, for the gene changes that lead to this type of cancer. A small number of medullary thyroid cancers may occur at the same time as Hirschsprung disease (chronic constipation that begins when a child is an infant), which has been found in some families with MEN2A syndrome. Hirschsprung disease may appear before other signs of MEN2A syndrome do.

Patients who are diagnosed with Hirschsprung disease should be checked for certain gene changes that cause MEN2A syndrome.


Familial medullary carcinoma of the thyroid (FMTC) is a type of MEN2A syndrome that causes medullary thyroid cancer. A diagnosis of FMTC may be made when two or more family members have medullary thyroid cancer and no family members have parathyroid or adrenal gland problems.

MEN2B syndrome

Patients with MEN2B syndrome may have a slender body build with long, thin arms and legs. The lips may appear thick and bumpy because of benign tumors in the mucous membranes. MEN2B syndrome may cause the following conditions:

  • Medullary thyroid cancer
  • Parathyroid hyperplasia
  • Adenomas
  • Pheochromocytoma
  • Nerve cell tumors in the mucous membranes or other places

How is Multiple Endocrine Neoplasia Syndrome Diagnosed in Children?

Tests used to diagnose and stage MEN syndromes depend on the signs and symptoms and the patient's family history. They may include:

  • Physical exam and history.
  • Blood chemistry studies.
  • Ultrasound.
  • MRI.
  • CT scan.
  • PET scan.
  • Fine-needle aspiration (FNA) or surgical biopsy.

Other tests and procedures used to diagnose MEN syndromes include the following:

Genetic testing: A laboratory test that analyzes cells or tissues to look for changes in a gene, chromosome, or protein. These changes may be a sign of a genetic disease or condition. They may also be linked to an increased risk of developing a specific disease or condition. Blood hormone studies: A procedure in which a blood sample is checked to measure the amounts of certain hormones released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. The blood may be checked for abnormal levels of thyroid-stimulating hormone (TSH). TSH is made by the pituitary gland in the brain. It stimulates the release of thyroid hormone and controls how fast follicular thyroid cells grow. The blood may also be checked for high levels of the hormone calcitonin or parathyroid hormone (PTH).

Radioactive iodine scan (RAI scan): A procedure to find areas in the body where thyroid cancer cells may be dividing quickly. Radioactive iodine (RAI) is used because only thyroid cells take up iodine. A very small amount of RAI is swallowed, travels through the blood, and collects in thyroid tissue and thyroid cancer cells anywhere in the body. Abnormal thyroid cells take up less iodine than normal thyroid cells do. Areas that do not take up the iodine normally are called cold spots. Cold spots show up lighter in the picture made by the scan. They can be either benign (not cancer) or malignant, so a biopsy is done to find out if they are cancer.

Sestamibi scan: A type of radionuclide scan used to find an overactive parathyroid gland. A very small amount of a radioactive substance called technetium 99 is injected into a vein and travels through the bloodstream to the parathyroid gland. The radioactive substance will collect in the overactive gland and show up brightly on a special camera that detects radioactivity.

Angiogram: A procedure to look at blood vessels and the flow of blood. A contrast dye is injected into a blood vessel. As the contrast dye moves through the blood vessel, x-rays are taken to see if there are any blockages.

Venous sampling for an overactive parathyroid gland: A procedure in which a sample of blood is taken from veins near the parathyroid glands. The sample is checked to measure the amount of parathyroid hormone released into the blood by each gland. Venous sampling may be done if blood tests show there is an overactive parathyroid gland but imaging tests don’t show which one it is.

Somatostatin receptor scintigraphy: A type of radionuclide scan that may be used to find tumors. A very small amount of radioactive octreotide (a hormone that attaches to tumors) is injected into a vein and travels through the blood. The radioactive octreotide attaches to the tumor and a special camera that detects radioactivity is used to show where the tumors are in the body. This procedure is also called octreotide scan and SRS.

MIBG scan: A procedure used to find neuroendocrine tumors, such as pheochromocytoma. A very small amount of a substance called radioactive MIBG is injected into a vein and travels through the bloodstream. Neuroendocrine tumor cells take up the radioactive MIBG and are detected by a scanner. Scans may be taken over 1-3 days. An iodine solution may be given before or during the test to keep the thyroid gland from absorbing too much of the MIBG.

Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of catecholamines in the urine. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher- or lower-than-normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts may be a sign of pheochromocytoma.

Pentagastrin stimulation test: A test in which blood samples are checked to measure the amount of calcitonin in the blood. Calcium gluconate and pentagastrin are injected into the blood and then several blood samples are taken over the next 5 minutes. If the level of calcitonin in the blood increases, it may be a sign of medullary thyroid cancer.

What Is the Treatment for Multiple Endocrine Neoplasia Syndrome in Children?

There are several types of MEN syndrome, and each type may need different treatment:

  • Patients with the MEN1 syndrome are treated for parathyroid, pancreatic and pituitary tumors.
  • Patients with the MEN1 syndrome and primary hyperparathyroidism may have surgery to remove at least three parathyroid glands and the thymus.
  • Patients with the MEN2A syndrome usually have surgery to remove the thyroid by age 5 or earlier if genetic tests show certain changes in the RET gene.
  • The surgery is done to diagnose cancer or to prevent cancer from forming or spreading.
  • Infants with the MEN2B syndrome may have surgery to remove the thyroid to prevent cancer.
  • Children with the MEN2B syndrome who have medullary thyroid cancer may be treated with targeted therapy (kinase inhibitor).
  • Patients with Hirschsprung disease and certain gene changes may have the thyroid removed to prevent cancer.

Treatment of recurrent MEN syndrome in children may include the following:

  • A clinical trial that checks a sample of the patient's tumor for certain gene changes. The type of targeted therapy that will be given to the patient depends on the type of gene change.

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Last updated Oct. 6, 2017