Evidence of multicentric origin of the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome) in a large family in the Netherlands: Diagnostic and therapeutic implications

Abstract The occurrence of simultaneous tumors in different organs and the multicentric localization of the tumors in each of these organs are discussed on the basis of the findings in six patients belonging to a large kindred with Sipple's syndrome and in patients with Sipple's syndrome not belonging to this kindred, as well as the data in the literature. The high number of accessory pheochromocytomas in this family and in the other patients with Sipple's syndrome was striking. Both the pheochromocytomas and the accessories were found in the form of both cortical nodules and complete adrenal glands with hyperplastic medullary tissue. The invariable occurrence of pheochromocytoma changes in accessory adrenal tissue in this family and in other cases supports and demonstrates the multicentricity of tumor development in Sipple's syndrome. The aim of surgical treatment should be to remove all the pheochromocytoma tissue identified in the adrenal glands, the celiac plexus and side chain regions, thereby reducing the chance of recurrence of the symptoms in these patients and the need for repeated surgical intervention. However, more extensive exploration of the chest, cervical area, etc., to attempt curative surgery, is too destructive to be justifiable. The medullary thyroid carcinoma, which is also multicentric in origin, is, on the contrary, a dangerous tumor for which total thyroidectomy with extensive neck exploration is obligatory, preferably in an early phase. A modified short calcium test which is especially sensitive in this early phase, is described for screening for medullary thyroid carcinoma.