Clues to the Diagnosis of Pheochromocytoma from the Differential Tissue Metabolism of Catecholamines

Abstract

Understanding the utility and limitations of measurements of urine or plasma levels of catecholamines and their metabolites for diagnosis of pheochromocytoma requires an understanding of catecholamine metabolism. This is not restricted to knowledge of the sources of catecholamines and the pathways of their metabolism, but more importantly requires an appreciation of how catecholamines are metabolized differentially within neuronal and extraneuronal compartments, among tissues and organs and before and after their entry into the bloodstream. In contrast to metabolites, the metanephrines (normetanephrine and rnetanephrine) are formed exclusively in extraneuronal tissues from O -methylation of norepinephrine and epinephrine. Plasma metanephrines are formed extraneuronally and to a large extent within chromaffin tissues, for example, adrenal medulla and pheochromocytomas. Therefore, these metabolites are better markers for a pheochromocytoma than are other catecholamine metabolites, which are derived mainly from metabolism of norepinephrine within sympathetic nerves. Pheochromocytomas may be quiescent and not secrete catecholamines, whereas they always appear to actively metabolize catecholamines to the free metanephrines. Thus, plasma measurements of free metanephrines offer a superior and more reliable test over plasma catecholamines for diagnosis of pheochromocytoma.