Adrenal medullary hyperplasia: a clinicopathologic study of four cases

This study presents the clinicopathologic findings in four new cases of adrenal medullary hyperplasia. The patients presented with episodic hypertension frequently associated with palpitations, headache, and diaphoresis. All four had elevated urinary catecholamine levels during attacks, and were thought clinically to have a pheochromocytoma. In each case laparotomy revealed a diffusely enlarged adrenal gland without a discrete tumor. Histologic examination of the adrenals demonstrated a diffuse and nodular expansion of the medulla confirmed by morphometric study. Of the four patients, three underwent unilateral and one bilateral adrenalectomy. Two patients who underwent unilateral adrenalectomy have been free of symptoms for three years. Thus, it would appear that adrenal medullary hyperplasia may occur unilaterally or asynchronously in the two glands. The bilaterally adrenalectomized patient has had persistent attacks, suggesting that the stimulus to adrenal medullary hyperplasia may possible affect other chromaffin tissues. On the basis of our cases and a review of the literature, we propose the following criteria for the diagnosis of adrenal medullary hyperplasia: a clinical history of episodic attacks suggesting pheochromocytoma (generally with associated increased urinary catecholamine levels), an adrenal gland showing diffuse expansion of the medulla into the alae or tail of the gland with or without nodule formation, a medulla composed of enlarged cells with or without pleomorphism, and, most important, an increased medulla/cortex ratio, together with an increased calculated medullary weight as determined by morphometric analysis.