Multiple endocrine neoplasia type IIB

is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs. Organs commonly involved include the thyroid and adrenal medulla. The spectrum of thyroid and adrenal medullary disease is similar to that in MEN-2A. However, unlike MEN-2A, patients with MEN-2B:

• Do not develop primary hyperparathyroidism
• Develop extraendocrine manifestations: ganglioneuromas of mucosal sites (gastrointestinal tract, lips, tongue) and marfanoid habitus^[1]

95% percent of MEN 2B cases result from a single amino acid substitution in the RET protein. More than 50% are de novo mutations and thus appear to be sporadic rather than familial.

Symptoms and Signs

About 50% of patients have the complete syndrome with mucosal neuromas, pheochromocytomas, and medullary thyroid carcinoma (MTC). Fewer than 10% have neuromas and pheochromocytomas alone, whereas the remaining patients have neuromas and medullary carcinoma of the thyroid without pheochromocytoma.

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 mucosa. The eyelids, conjunctiva, and corneas also commonly develop neuromas. Thickened eyelids and diffusely hypertrophied lips are characteristic. GI abnormalities related to altered motility (constipation, diarrhea, and, occasionally, megacolon) are common and thought to result from diffuse intestinal ganglioneuromatosis. Patients may have a marfanoid habitus. Skeletal abnormalities of the spine (lordosis, kyphosis, scoliosis), pes cavus, and talipes equinovarus are common.

MTC and pheochromocytoma resemble the corresponding disorders in MEN 2A syndrome; both tend to be bilateral and multicentric. MTC, however, tends to be particularly aggressive in MEN 2B and may be present in very young children.

Although the neuromas, facial characteristics, and GI disorders are present at an early age, the syndrome may not be recognized until MTC or pheochromocytoma presents in later life.

Diagnosis

• Clinical suspicion
• Genetic testing
• Plasma free metanephrine or urinary catecholamine levels
• Pheochromocytoma localization with MRI or CT

Treatment

• 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 in infancy or early childhood.