The Relationship between Enzyme Activity and the Catecholamine Content and Secretion of Pheochromocytomas*

We evaluated 7 patients (5 familial and 2 sporadic) with pheochromocytomas. As 4 of the patients had bilateral pheochromocytomas, we were able to analyze 11 tumors. We also analyzed 7 adrenal medullae from 4 patients undergoing bilateral adrenalectomy for palliation of metastatic breast carcinoma. There was a substantial quantity of dopamine (DA) in both the pheochromocytomas (658 μg/g) and the normal adrenal medullae (254 μg/g). Dopamine-β-hydroxylase (DBH) activity was present in both the pheochromocytomas (29.3 nmol/mg·min) and the normal adrenal medullae (8.6 nmol/mg·min). There was no significant correlation between the DBH activity and the DA or norepinephrine concentration of the pheochromocytomas. All of the pheochromocytomas (84 pmol/mg·min) and normal adrenal medullae (52 pmol/mg·min) had phenylethanolamine-N-methyltransferase (PNMT) activity, although some of the pheochromocytomas did not synthesize or secrete epinephrine (E). Although the correlation coefficient between the PNMT activity and the E concentration in the pheochromocytomas (r = 0.55) failed to achieve statistical significance, in general, those with the greatest PNMT activities had the highest E concentrations. The catechol-O-methyltransferase activities of pheochromocytomas (30 pmol/mg·min) and normal adrenal medullae (43 pmol/mg·min) were comparable. The monoamine oxidase activity of the pheochromocytomas (202 pmol/mg·min) was significantly less than that of the normal adrenal medullae (676 pmol/mg·min). There was no correlation between the monoamine oxidase and/or the catechol-O-methyltransferase activity of the pheochromocytomas and the size, catecholamine concentration, or clinical manifestation of the pheochromocytomas. We measured the serotonin concentration in 12 pheochromocytomas (10 of the above plus 2 additional sporadic pheochromocytomas). The serotonin concentration of the familial pheochromocytomas (4.34 ± 0.77 μg/g) was significantly higher than that of the sporadic pheochromocytomas (0.49 ± 0.19 μg/g). We conclude that 1) the majority of pheochromocytomas contain but do not secrete substantial amounts of DA; 2) norepinephrine and E production by pheochromocytomas are not dependent solely on DBH and PNMT activity, respectively; 3) the size of a pheochromocytoma is not solely dependent on its monoamine oxidase and catechol-O-methyltransferase activities; and 4) familial pheochromocytomas probably have greater serotonin concentrations than sporadic pheochromocytomas.