Total metanephrines

Normetanephrine andmetanephrine are metabolic products of norepinephrine and epinephrine, respectively, and are formed by the action of catechol-0-methyltransferase without deamination. As a result of active neuronal reuptake and deamination of norepinephrine, normetanephrine normally represents <5% of the total norepinephrine excretion products in urine. Metanephrine, however, even with its lower urinary concentration relative to normetanephrine, represents a major excretion product of epinephrine. The metanephrines are excreted in both conjugated and unconjugated forms. Unlike the catecholamines, total metanephrine excretion is not significantly influenced by diet. As a result, the total metanephrines are routinely measured after acid hydrolysis or sulfatase pretreatment. 

Measurement of total urinary metanephrines using spectrophotometric methods has also been reported." " After sample hydrolysis and isolation of metanephrines by ion-exchange chromatography, the hydroxyl- and amino-containing side-chains were oxidatively cleaved by periodate. Oxidation of both NM and MN resulted in the formation of a common end product, vanillin, which was measured spectrophotometricafly at 360 nm. This method was, however, susceptible to interferences from other compounds such as methylglucamine and the 4-hydroxylated metabolite of propranolol." Furthermore, the method did not differentiate between NM and MN, and results were only semi-quantitative for grossly increased concentrations of total metanephrines." " ... 

R.F. Coward and P. Smith, Recovery of total metanephrines from urine and their estimation by paper chromatography, Clin. Chim. Acta, 14, 672-678 (1966). 

A sensitive spectrophotometric method based on the strong absorption of the aminochrome-sodium bisulfite addition products (see Section IV, F) at ca. 350 m/x. has been described recently by van Espen128and Oesterling and Tse 277-278 for determining total catecholamines. While not as sensitive as the fluorimetric procedures, this method is considerably more sensitive than the older colorimetric methods based on the visible absorption peak of the aminochromes. Also, it does not have many of the disadvantages (e.g. costly equipment and unstable blanks) often associated with fluorimetric techniques. The basic procedure can be satisfactorily applied to the differential determination of mixtures of adrenaline, noradrenaline, dopamine, metanephrine, and normetanephrine.178... 

Metanephrines represent metabolites of the catecholamines urinary levels are greater than total catecholamines but less than those of VMA. In tumors, variations in the metabolic pathways can cause an increase in the metanephrines alone. 

Since dopamine is present in sympathetic nervous tissue as a precursor of norepinephrine, and it has a separate metabolic pathway that yields homovanillic acid (HVA), tumors such as neuroblastomas may cause elevations of the urinary dopamine and its metabolite HVA. In some cases these elevations have been observed with normal VMA, total catecholamine, and metanephrine. Urinary HVA is usually normal in patients with phenochromocytoma. Increased HVA is found in special fluids of patients with Parkinson s disease treated with L-dopa. 

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