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Multiple Endocrine Neoplasia, Type 2B (MEN 2B)

(Mucosal Neuroma Syndrome; Multiple Endocrine Adenomatosis, Type 2B)


Lawrence S. Kirschner

, MD, PhD, The Ohio State University;

Pamela Brock

, MS, CGC, The Ohio State University

Reviewed/Revised Jun 2023
Topic Resources

Multiple endocrine neoplasia, type 2B (MEN 2B) is an autosomal dominant syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, multiple mucosal neuromas and intestinal ganglioneuromas, and often a marfanoid habitus and other skeletal abnormalities. Symptoms depend on the glandular abnormalities present. Diagnosis is confirmed by genetic testing. Hormonal and imaging tests help locate the tumors, which are removed surgically when possible.

Symptoms and Signs of MEN 2B

Often, mucosal neuromas are the earliest sign, and they occur in most or all patients. Neuromas appear as small glistening bumps on the lips, tongue, and buccal mucosae.

The eyelids, conjunctivae, and corneas also commonly develop neuromas; infants are often unable to make tears. Thickened eyelids and everted, diffusely hypertrophied lips are characteristic.

Gastrointestinal abnormalities related to altered motility (constipation, diarrhea, and, occasionally, megacolon) are common and thought to result from diffuse intestinal ganglioneuromatosis.

Patients almost always have a marfanoid habitus Symptoms and Signs Marfan syndrome consists of connective tissue anomalies resulting in ocular, skeletal, and cardiovascular abnormalities (eg, dilation of ascending aorta, which can lead to aortic dissection)... read more Symptoms and Signs . Skeletal abnormalities are common, including deformities of the spine (lordosis, kyphosis, scoliosis), slipped capital femoral epiphyses, dolichocephaly (hull-shaped skull, also called scaphocephaly), pes cavus, and talipes equinovarus.

Medullary thyroid carcinoma and pheochromocytoma resemble the corresponding disorders in MEN 2A syndrome Symptoms and Signs Multiple endocrine neoplasia, type 2A (MEN 2A) is an autosomal dominant syndrome characterized by medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas (causing... read more Symptoms and Signs ; both tend to be bilateral and multicentric. Medullary thyroid carcinoma, however, tends to be particularly aggressive in MEN 2B and may be present in very young children.

Although the neuromas, facial characteristics, and gastrointestinal disorders are present at an early age, the syndrome may not be recognized until medullary thyroid carcinoma or pheochromocytoma manifests in later life.

Diagnosis of MEN 2B

  • Serum calcitonin levels

  • Plasma free metanephrines and urinary catecholamine levels

  • Neck CT or MRI

  • Pheochromocytoma localization with magnetic resonance imaging (MRI) or computed tomography (CT)

  • Genetic testing

MEN 2B is suspected in patients with a family history of MEN 2B, pheochromocytoma, multiple mucosal neuromas, or medullary thyroid carcinoma. Genetic testing is highly accurate and is done to confirm the disorder. Genetic testing Genetic screening Multiple endocrine neoplasia, type 2A (MEN 2A) is an autosomal dominant syndrome characterized by medullary carcinoma of the thyroid, pheochromocytoma, parathyroid hyperplasia or adenomas (causing... read more Genetic screening also is done to screen 1st-degree relatives and any symptomatic family members of patients with MEN 2B, as in MEN 2A.

MRI or CT is used to search for pheochromocytomas and medullary thyroid carcinoma.

Treatment of MEN 2B

  • Surgical excision of identified tumors

  • Prophylactic thyroidectomy

Affected patients should have total thyroidectomy as soon as the diagnosis is established. Pheochromocytoma, if present, should be removed before thyroidectomy is done.

Gene carriers should undergo prophylactic thyroidectomy before age 1 year.

Key Points

  • Multiple endocrine neoplasia, type 2B (MEN 2B) has a mutation of the same gene as in MEN 2A and manifests similarly except for the absence of hyperparathyroidism, the presence of more aggressive medullary thyroid carcinoma and the presence of multiple mucosal neuromas and a marfanoid habitus.

  • Patients should have genetic testing for RET proto-oncogene mutations, serum calcitonin measurement, blood or urine tests for pheochromocytoma, and imaging studies of the neck and adrenal glands.

  • Pheochromocytoma is excised and prophylactic thyroidectomy is done.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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