Multiple endocrine neoplasia, type 2b

Multiple endocrine neoplasia, type 2b, is a disorder of unknown etiology with major involvement of the thyroid and adrenal glands, the autonomic nervous system, and connective tissue. It is transmissible with an autosomal dominant pattern of inheritance, but since most cases are not familial, they presumably represent mutations. The thyroid gland exhibits bilateral medullary carcinoma, which is a metastasizing lethal neoplasm in the syndrome requiring total thyroidectomy once abnormal basal or stimulated concentrations of plasma immunoreactive calcitonin have been demonstrated. The adrenal medullary tumors--pheochromocytomas--although rarely malignant, are potentially lethal because of their cardiovascular effects. Since the adrenal involvement is usually bilateral, total bilateral adrenalectomy with excision of any extraadrenal paraganglioma is the surgical treatment. Parathyroid hyperplasia occurs rarely in the syndrome. Treatment of it should be conservative, that is, limited to excision of enlarged parathyroid glands. Major portions of the autonomic nervous system, both sympathetic and parasympathetic, nerves and ganglia, exhibit hypertrophy, hyperplasia, and disorder of structure--a group of changes designated ganglioneuromatosis. This may be largely responsible for the striking eye and oral findings--the hallmarks of the syndrome--and also for some of the serious symptoms and complications of the syndrome, particularly those referable to the alimentary tract. Ganglioneuromatosis is also found in the salivary glands, pancreas, gallbladder, upper respiratory tract, and urinary bladder. The connective tissue abnormality is manifested by increased growth of long bones, ribs, and skull, resulting in a marfanoid habitus, and also by skeletal and joint abnormalities together with increased laxity of ligaments. Ninety cases of MEN 2b have been reported, and although follow-up information is incomplete, 27 patients (30 percent) are known to be dead because of the syndrome. The causes of death have been medullary thyroid carcinoma (15 deaths), pheochromocytoma (10 deaths), and alimentary tract complications (2 deaths). An additional 21 patients (22 percent) are known to have metastatic MTC. We are aware of only 2 patients who, 5 years after thyroidectomy, have apparently been cured of MTC, but both are still at risk for adrenal medullary disease. MEN 2b is, therefore, a very serious disorder that requires urgent treatment of the endocrine tumors. Fortunately, the majority of patients with the syndrome are easily recognized because of an abnormal phenotype typified by thick, bumpy lips and a marfanoid habitus. Since these findings signal high risk for the potentially lethal endocrine neoplasms, patients having the characteristic appearance need evaluation of thyroidal C-cell and adrenal medullary function.