Adrenal medullary hyperplasia in familial medullary thyroid carcinoma

The syndrome of medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia, type II multiple endocrine adenomatosis (MEA II), is inherited as an autosomal dominant trait. Both the thyroid and adrenal medullary tumors in this syndrome are frequently bilateral and multicentric. While the thyroid tumors in type II MEA have been shown recently to arise on a background of diffuse C cell hyperplasia, the histogenesis of the pheochromocytomas has not been specifically studied. In a review of 10 cases, the pheochromocytomas were bilateral and/or multicentric in 7 patients. In 2 patients with unilateral single tumors, the opposite adrenals were said to be normal by palpation or arteriography. The adrenal glands of 1 patient whose urinary vallinyl mandelic acid (VMA) values had ranged from 5.0 to 8.2 mg/24 hr (normal VMA, up to 8 mg/24 hr) revealed a diffuse expansion of both medullary regions in addition to a small nodule in the right medulla. Morphometric studies revealed hypertrophy of individual cells, as well as a diffuse medullary hyperplasia characterized by finger like protrusions of the medulla into the overlying cortex. Individual cells exhibited irregularly shaped bizarre hyperchromatic nuclei, granular or vacuolated cytoplasm, and numerous intracytoplasmic hyaline inclusions. Similar hyperplastic changes were noted frequently in the adrenal medullary regions adjacent to the pheochromocytomas in the remaining patients of this series. The bilateral and multicentric pheochromocytomas seen in patients with type II MEA may develop on a background of diffuse medullary hyperplasia.