Urine metanephrines

Chan EC, Ho PC. 2000. High-performance liquid chromatog-raphy/atmospheric pressure chemical ionization mass spec-trometric method for the analysis of catecholamines and metanephrines in human urine. Rapid Commun Mass Spectrom 14 1959. 

Peterson ZD, Collins DC, BowerbankCR, Lee ML, Graves SW. 2002. Determination of catecholamines and metanephrines in urine by capillary electrophoresis-electrospray ioniza-tion-time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 776 221. 

Degradation of catecholamines The catecholamines are inacti vated by oxidative deamination catalyzed by monoamine oxidase (MAO), and by O-methylation carried out by catechol-O-methyl-transferase (COMT, Figure 21.15). The two reactions can occur in either order. The aldehyde products of the MAO reaction are axi dized to the corresponding acids. The metabolic products of these reactions are excreted in the urine as vanillylmandelic acid, metanephrine, and normetanephrine. 

Potential fates of recaptured norepinephrine Once norepinephrine reenters the cytoplasm of the adrenergic neuron it may be taken up into adrenergic vesicles via the amine transporter system and be sequestered for release by another action potential or persist in a protected pool. Alternatively, norepinephrine can be oxidized by monoamine oxidase (MAO) present in neuronal mitochondria. The inactive products of norepinephrine metabolism are excreted in the urine as vanillylmandelic acid (VMA), metanephrine and normetanephrine. 

Biotransformations Epinephrine, like the other catecholamines, is metabolized by two enzymatic pathways COMT, which has S-adenosylmethionine as a cofactor, and MAO (see Figure 6.3). The final metabolites found in the urine are metanephrine and vanillylmandelic acid. [Note Urine also contains normeta-nephrine, a product of norepinephrine metabolism.]... 

Four catecholamines have been found in increased amounts in the urine after injury (W2), metanephrine, normetanephrine, iV-methyl-metanephrine, and 3-methoxytyramine. The JV-methylmetanephrine probably indicates an increased production of epinephrine (Cll). The increase in norepinephrine production is relatively greater than that of epinephrine, suggesting an active release of hormone from sympathetic nerve tissue as well as from the adrenal medulla. 

Coulometric detectors are also used. When placed in a series, such detectors are used to detect and quantify coeluting compounds that differ in their half-wave potentials (the potential at half-signal maximum) by at least 60 mV. These detectors are extremely selective and sensitive, with reasonably wide linear response ranges. They are used in the clinical laboratory for the analysis of metanephrines, vanil-lymandelic acid, homovaniUic acid, and 5-hydroxyindole acetic acid in human urine without extensive sample preparation. 

Findings that none of the traditionally used biochemical tests could reliably detect aU cases of pheochromocytomas led to recommendations that biochemical testing should include a combination of measurements of catecholamines and catecholamine metabolites. VMA is excreted in urine in large amounts, which makes measurement of this metabolite a simple, easy to implement, and time-honored test for diagnosis of pheochromocytomas. Numerous studies have now made it clear, however, that measurements of urinary VMA provide a relatively insensitive diagnostic test with limited value for initial testing for pheochromocytomas. Therefore the usual recommendation has been that biochemical testing should include measurements of urinary or plasma catecholamines and urinary metanephrines. 

The basis for the high diagnostic efficacy of plasma free metanephrines is explained by several factors (1) plasma free metanephrines are produced by metabolism of catecholamines within pheochromocytomas, a process that occurs continuously and independently of variations in catecholamine release by tumors (2) normally only small amounts of metanephrines are produced in the body, and these are relatively unresponsive to sympathoadrenal activation compared with the parent amines and (3) VMA and the metanephrines commonly measured in urine are different metabofites from the free metanephrines measured in plasma, and are produced in different parts of the body by metabolic processes not directly related to the tumor itself." ... 

Additional markers of catecholamine overproduction have been employed to improve the biochemical detection of neuroblastomas. Free dopamine may be abnormal in urine from neuroblastoma patients with VMA and HVA excretion. Combined testing for VMA, HVA, and dopamine may therefore improve tumor detection, and in 1993 an international consensus report on neuroblastoma diagnosis added dopamine to the Hst of acceptable measurements to document the adrenergic nature of the tumor. Plasma measurements of dopamine and L-dopa, the amino acid precursor of dopamine, may also have clinical value and allow the alternate use of plasma. Measurement of methylated metabolites, especially normetanephrine, has also been explored. When urinary normetanephrine, metanephrine, methoxytyra-mine, dopamine, norepinephrine, VMA, and HVA were measured, clinical sensitivity for detection of neuroblastomas was 97% to 100% when results of normetanephrine testing were coupled either with VMA in the infants or with HVA in children greater than age 1. Even with an extended panel of catecholamines and metabolite measurements, a low incidence of nonsecreting tumors continues to be identified and should be considered in the interpretation of a negative test result. 

In contrast to the catecholamines, measurements of urinary metanephrines and VMA are still based in some routine laboratories on the early spectrophotometric assays developed by Pisano, Crout, and others in the late 1950s and early 1960s. Despite subsequent development of a variety of preanalytical cleanup and extraction procedures, these assays remain susceptible to analytical interference. They are also restricted to measurements in urine. Another limitation for spectrophotometric or fiuorometric assays of urinary metanephrines is that these methods do not allow separate (fractionated) measurements of normetanephrine and metanephrine. 

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. 

Buu NT, Angers M, Chevalier D, Kuchel O. A new method for the simultaneous analysis of free and sulfoconjugated normetanephrine, metanephrine, and 3-methoxytyramine in human urine by HPLC with electrochemical detection. J Lab Clin Med 1984 104 425-32. 

Kaplan NM, Kramer NJ, Holland OB, Sheps SG, Gomez-Sanchez C. Single-voided urine metanephrine assays in screening for pheochromocytoma. Arch Intern Med 1977 137 190-3. 

Pisano J. A simple analysis of normetanephrine and metanephrine in urine. Clin Chim Acta 1960 5 406-14. 

Smith E. Metanephrine and normetanephrine in human urine method and results. J Lab Clin Med 1962 60 212-23. 

Taniguchi K, Kakimoto Y, Armstrong M. Quantitative determination of metanephrine and normetanephrine in urine. J Lab Clin Med 1964 64 469-84. 

Chan et developed an assay for the simultaneous determination of catecholamines and metanephrines using FMOC derivatization. The assay is convenient for the simultaneous analysis of NM, MN, E and DA in human urine sample without prior extraction procedures. In this study, urine was directly derivatized and subjected to a simple extraction step with... 

Catecholamines and metanephrines are prone to oxidative conversion to their corresponding quinones, 2 hence proper storage and preservation of 24-h urine samples after collection from patients is essential for accurate quantitation of these compounds. Various groups have reported stability studies of catecholamines in biological fluids. Boomsma et al. 

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