Deficiency of Dopamine-β-hydroxlase: A New Mechanism for Normotensive Pheochromocytomas

Although the majority of patients with pheochromocytomas have hypertension due to excessive catecholamine secretion from their tumors, occasional patients with these tumors may be normotensive. The case of a 28-year-old normotensive man with bilateral pheochromocytomas is compared with those of four hypertensive patients with pheochromocytomas. The normotensive patient’s tumors contained a large amount of dopamine, a small amount of norepinephrine, and no epinephrine. The pheochromocytomas of the hypertensive patients contained large amounts of dopamine, norepinephrine, and in some tumors, epinephrine. The small quantity of norepinephrine in the pheochromocytomas of the normotensive patient was due to a deficiency of tumor dopamine- β -hydroxylase. The small amount of epinephrine in his pheochromocytomas was due to a deficiency of phenylethanolamine-N-methyltransferase, as well as a deficiency of the phenylethanolamine-N-methyltransferase substrate norepinephrine. Many of the electron-dense secretory granules in the predominantly dopamine-containing pheochromocytomas of the normotensive patient had the morphologic appearance of granules of norepinephrine. However, in general, the granules in these tumors were more variable in size and shape, and on the average, tended to be slightly smaller than the granules in one of the predominantly norepinephrine-containing pheochromocytomas from a hypertensive patient which was studied ultrastructurally. The large amount of homo vanillic acid in the preoperative urine, but not the postoperative urine, of the normotensive patient suggests that his tumor was secreting dopamine. The normal excretion of homovanillic acid by the hypertensive patients suggests that their pheochromocytomas did not secrete dopamine. A possible mechanism for the absence of hypertension in patients with pheochromocytomas is a deficiency of tumor dopamine- β -hydroxylase activity, with a resulting increase of dopamine secretion and decrease of norepinephrine secretion.