Mucosal neuroma, pheochromocytoma and medullary thyroid carcinoma: multiple endocrine neoplasia type 3

1. Three members of a kindred and a fourth unrelated individual demonstrating the syndrome of mucosal neuroma, bumpy lips, marfanoid habitus, medullary thyroid carcinoma and pheochromocytoma are reported, and the literature pertaining to this syndrome has been reviewed. 2. There are currently 41 definite and 16 additional probable reported cases manifesting the syndrome of mucosal neuroma, bumpy lips, pheochromocytoma and medullary thyroid carcinoma. Mucosal neuroma was present in all patients. Medullary thyroid carcinoma was histologically proved in 38 cases. Pheochromocytoma was documented in 19 patients with a probable diagnois in another 4 patients. Only one patient was noted to have hypercalcemia associated with parathyroid adenoma. Associated abnormalities seen in this syndrome include hypertrophied corneal nerves, skeletal defects and gastrointestinal tract abnormalities. 3. The relationship of this syndrome to other types of multiple endocrine neoplasia syndromes and the phakomatoses is also discussed. This syndrome appears to be distinct from the entity of multiple endocrine neoplasia type 2. We suggest that this syndrome be called multiple endocrine neoplasia type 3, following the classification originally proposed by Steiner et al. 4. MEN type 3 appears to be inherited as an autosomal dominant disorder. Many apparently non-familial cases have been reported, but due to inadequate information regarding family history it may be possible that some of these cases also had other affected family members. 5. This syndrome most likely results from a dysplasia of neuroectodermal tissue. The pathogenesis of this syndrome is discussed and evidence supporting the hypothesis is reviewed. 6. The importance of diagnosing the syndrome at an early stage and of investigating the relatives of a patient manifesting this potentially fatal syndrome are stressed. 7. Plasma calcitonin measurement following calcium infusion is extremely useful as a screening procedure for the diagnosis of medullary thyroid carcinoma, when the patients are completely asymptomatic and routine thyroid function tests are normal. Affected individuals should also be periodically screened for the development of pheochromocytoma.