Sipple's Syndrome: Medullary Thyroid Carcinoma, Pheochromocytoma, and Parathyroid Disease

Abstract

Sipple's syndrome is medullary carcinoma of the thyroid, pheochromocytoma, and parathyroid disease. It is transmitted as an autosomal dominant trait with a high degree of penetrance. Medullary carcinoma of the thyroid can be accurately diagnosed early by measuring serum calcitonin, often when all other diagnostic tests are negative. This carcinoma has a unique radiographic appearance, is usually bilateral, and requires total thyroidectomy; the enzyme histaminase serves as a sensitive biochemical marker of the tumor in tissues and is useful for detecting metastatic lesions postoperatively. The pheochromocytomas are similar to those occurring sporadically, except that they are more often bilateral and often unresponsive to provocative diagnostic tests. Parathyroid hyperplasia is a definite part of this syndrome, although often physiologically inconsequential and therefore diagnosed only at surgery for the thyroid carcinoma. The parathyroid hyperplasia is probably a genetic phenomenon rather than a reactive one. Recent biochemical findings support the hypothesis that the diverse features of Sipple's syndrome are caused by a dysplasia of neural crest cells.