PLASMA METADRENALINES - DO THEY PROVIDE USEFUL INFORMATION ABOUT SYMPATHOADRENAL FUNCTION AND CATECHOLAMINE METABOLISM

1. The clinical utility of plasma metadrenalines for examination of sy mpatho-adrenal function and catecholamine metabolism was assessed from plasma measurements of these metabolites in a number of clinical cond itions (hypertension, cardiac failure, bilateral adrenalectomy and X-c hromosomal deletions of the gene for monoamine oxidase), and before an d during activation of sympathetic outflow or infusions of noradrenali ne and adrenaline. 2. Plasma concentrations of normetadrenaline were l ess than 25% of those of noradrenaline, concentrations of metadrenalin e and adrenaline were similar and those of sulphate-conjugated metadre nalines were 20- to 30-fold higher than free metradrenalines. Hyperten sive patients had elevated plasma concentrations of adrenaline, noradr enaline and conjugated but not free metradrenalines. Cardiac failure p atients had 2- to 4-fold increases in plasma noradrenaline and free an d conjugated normetadrenaline. Adrenalectomy resulted in undetectable plasma concentrations of adrenaline, 91-97% decreases in free and conj ugated metadrenaline and a 40% decrease in normetadrenaline relative t o noradrenaline. Patients with X-chromosomal deletions of the gene for monoamine oxidase had 6- and 16-fold increases in plasma free and con jugated normetadrenaline and 2- and 4-fold increases in free and conju gated metadrenaline. 3. Infusion of catecholamines increased plasma co ncentrations of free metadrenalines by less than 6% of increases in pr ecursor amines, indicating that most plasma normetadrenaline (84%) and metadrenaline (90%) is derived from metabolism of catecholamines befo re their entry into the circulation. Considerable O-methylation of cat echolamines within the adrenals explains why sympatho-adrenal activati on resulted in smaller proportional increases in plasma metadrenalines than catecholamines. 4. Plasma metadrenalines provide supplementary i nformation about sympatho-adrenal activity to that provided by catecho lamines, but are more useful for examination of the extraneuronal inac tivation of catecholamines, particularly detection of neurochemical ph enotypes in genetic disorders of catecholamine metabolism. Significant formation of metadrenalines within chromaffin tissue explains why mea surements of plasma metadrenalines provide an extraordinarily sensitiv e method for diagnosis of phaeochromocytoma.