Catecholamines metabolites

Measurement of catecholamine metabolites can provide insight into the rate of release or turnover of catecholamines in the brain. In clinical studies, metabolites of catecholamines are generally assayed in the CSF because the large quantities derived from the peripheral sympa-thomedullary system obscure the small contribution from the brain to urinary concentrations. However, acid metabolites are actively excreted from the CSF more reliable estimates of turnover in the brain are obtained when this transport process is blocked by pretreatment with the drug probenecid. 

Jones ED, Maas JW, Dekirmenjian H, et al Urinary catecholamine metabolites during behavioral changes in a patient with manic-depressive cycles. Science 179 300-302, 1973... 

Methenamine mandelate, 1 g four times daily, or methen-amine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4-12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites. 

Anggard, E. and Goran, S., Gas chromatography of catecholamine metabolites using electron capture detection and mass spectrometry, Anal. Chem., 41, 1250, 1969. 

Catecholamines and Some Catecholamine Metabolites in Human Urine 16 293... 

Catechol Amine Biosynthesis and MetaboUsm, Assay of Enzymes of Catecholamines and Catecholamine Metabolites, Estimation of Total (Free + Conjugated), in... 

Diagnostic tests include measurement of catecholamine metabolites in urine followed by catecholamine concentrations in blood when the urine results are equivocal or high. With modem analytical techniques interference by drugs and diet is less troublesome than formerly. 

The primary metabolites of dopamine are homovanillic acid and dihydroxyphenylacetic acid (75%) and norepinephrine (25%). The primary metabolites of epinephrine and norepinephrine are vanilylmandelic acid and 3-methoxy-4-hydroxy-phenethyleneglycol. Catecholamine metabolites and their conjugates are excreted in urine. 

Estrogen and progesterone receptors Catecholamine metabolites Hydroxyproline Lipid-associated sialic add Polyaminc... 

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. 

Deficiencies of tyrosine hydroxylase or of enzymes involved in production of tetrahydrobiopterin cofactor (e.g., dopa-responsive dystonia) usually result in presentation of severe neurological abnormalities in early childhood. Depending on the exact mutation, deficiencies of tyrosine hydroxylase can involve moderate to severe loss of enzyme activity, most accurately diagnosed by low cerebrospinal fluid levels of catecholamine metabolites, such as MHPG and HVA, but normal levels of In the autosomal... 

Because of the possible errors resulting from incomplete 24-hour urine collections or uncontrolled influences of physical activity, some investigators advocate spot or overnight urine collectionsd Correction for differences in duration of collection is achieved by normalizing catecholamine or catecholamine metabolite excretion against urinary creatinine excretion. Additional considerations for urine collected under these conditions include dietary protein, muscle mass, level of physical activity, and time of day, all of which impact creatinine excretion and may further confound interpretation of results. ... 

Dietary constituents or drugs can either cause direct analytical interference in assays or influence the physiological processes that determine plasma and urinary levels of catecholamines and catecholamine metabolites. In the former circumstances, the interference can be highly variable depending on the particular measurement method. In the latter circumstances, interference is usually of a more general nature and independent of the measurement method (Table 29-6). 

Reference intervals for plasma and urinary catecholamines and catecholamine metabolites also differ according to sex and age. Females have lower plasma concentrations of epinephrine and metanephrine than males. Similarly, 24-hour urinary outputs of catecholamines and metanephrines are lower in women than men for epinephrine this difference remains significant when values are normalized for creatinine excretion Plasma levels of norepinephrine and normetanephrine increase with advancing age in adults, whereas plasma levels of epinephrine and metanephrine are little affected. Age-related increases in 24-hour urinary outputs of norepinephrine and normetanephrine have also been reported,but not consistently by all studies. In general, the influences of age... 

Vanillylmandehc Acid (VMAj is a major catecholamine metabolite formed by the actions of catechol-0-methyl-transferase and MAO. It is excreted by the kidney and represents an average of 40% to 50% of the urinary excretion production of norepinephrine and epinephrine. Norepinephrine is the major source of VMA, with metabolism through MHPG as the major pathway. VA4A is not significantly conjugated and therefore is measured without a hydrolysis step. VMA was first isolated and identified in the urine of a patient with a pheochromocytoma, and its analysis is commonly performed to detect the presence of pheochromocytomas and neuroblastomas. 

Candito M, Thyss A, Albertini M, Deville A, Politano S, Mariani R, Chambon P. Methylated catecholamine metabolites for diagnosis of neuroblastoma. Med Pediatr Oncol 1992 20 215-20. 

Laug WE, Siegel SE, Shaw KN, Landing B, Baptista J, Gutenstein M. Initial urinary catecholamine metabolite concentrations and prognosis in neuroblastoma. Pediatrics 1978 62 77-83. 

Marchese N, Canini S, Fabi L, Famularo L. Paediatric reference values for urinary catecholamine metabolites evaluated by high performance liquid chromatography and electrochemical detection. Eur J Clin Chem Clin Biochem 1997 35 533-7. 

Pritchard J, Barnes J, Germond S, Hartman O, deKraker J, Lewis I, et al. Stage and urine catecholamine metabolite excretion in neuroblastoma. Lancet 1989 1 514-5. 

E.A.M. Gerlo and C. Sevens, Urinary and plasma catecholamines and urinary catecholamine metabolites in pheochromocytoma diagnostic value in 19 cases, Clin. Chem.. 40, 250-256 (1994). T. Jan, B.E. Metzger and G. Baumann, Epinephrine-producing pheochromocytoma with hypertensive crisis after corticotrophin injection. Am. J. Med.. 89, 824-825 (1990). 

J.M.C. Gutteridge, Thin-layer chromatographic techniques for the investigation of abnormal urinary catecholamine metabolite patterns, Clin. Chim. Acta, 21, 211-216 (1968). 

An inca uscd production of cutcchuluinincs from a benign or malignuni tumour causes vasoconstriction. The increased catecholamine production may not be easy to confirm, as phaet)chromocytomas frequently secrete catecholamines episixlically. Urinary catecholamine metabolites (Fig.. 1) may not be elevated unless the patient has been symptomatic during the peritxl of urine collection. Plasma adrenaline and noradrenaline concentrations are usually increased but these measurements arc only available in a small number of centres. 

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