Vanillylmandelic Acid (VMA) 

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Vanillylmandelic acid (VMA), a metabolic by-product of norepinephrine and epinephrine, can be used to detect neuroblastoma and other tumors of neural crest origin.

The reference ranges of vanillylmandelic acid in children are as follows: [1, 2, 3]

Younger than 1 year: < 27 mg/g creatinine

Age 1-2 years: < 18 mg/g creatinine

Age 2-4 years: < 13 mg/g creatinine

Age 5-9 years: < 8.5 mg/g creatinine

Age 10-14 years: < 7 mg/g creatinine

The reference range in persons aged 15 years and older is 2-7 mg/24 hours.

Conditions associated with elevations in urinary vanillylmandelic acid (VMA) include the following:

Neuroblastoma

Pheochromocytoma

Other neural crest tumors (eg, ganglioblastoma, ganglioneuroma)

Severe anxiety/stress

Specifics for collection and panels depend on the specimen type.

24-hour urine is collected as follows:

Container: Plastic 10-mL urine tube

Collection method: 24-hour urine collection

Specimen volume: 5 mL

Other instructions: (1) Add 25 mL of 50% acetic acid to collection vessel as a preservative and (2) note patient age and total urine volume

Random urine (only for children < 15 years) is collected as follows:

Container: Plastic 10-mL urine tube

Collection method: Random urine specimen

Specimen volume: 5 mL

Other instructions: (1) Adjust urine pH to 1 to 5 with 50% acetic or hydrochloric (HCl) acid, (2) note patient age, and (3) urine creatinine measurement required

Related tests: Urine creatinine, urine catecholamines, plasma free metanephrines, urine metanephrines, urine homovanillic acid (HVA)

Elevated metabolic by-products of catecholamines—dihydroxyphenylalanine (DOPA), dopamine, norepinephrine, and epinephrine—can be detected in the urine of patients with neuroblastoma and other tumors of neural crest origin. DOPA and dopamine are metabolized into their final product, homovanillic acid (HVA), while norepinephrine and epinephrine are metabolized into vanillylmandelic acid (VMA).

The biochemical pathway is as follows:

DOPA

Dopamine

Norepinephrine → Normetanephrine → VMA and 3-methoxyphenylethyleneglcol (MHPG)

Epinephrine → Metanephrine → VMA and 3-methoxyphenylethyleneglcol (MHPG)

Ninety percent of neuroblastoma tumors secrete these by-products. Children with dedifferentiated tumors tend to excrete higher levels of HVA than vanillylmandelic acid because these tumors have lost the final enzymatic pathway that converts HVA to vanillylmandelic acid. A low ratio of vanillylmandelic acid to HVA is consistent with a poorly differentiated tumor and indicates a poor prognosis.

In the evaluation of pheochromocytoma, vanillylmandelic acid is now considered the least-specific test for catecholamine metabolites, with a false-positive rate greater than 15%. Measurement of metanephrine, an intermediate metabolite between epinephrine and vanillylmandelic acid, is now considered the most sensitive and specific test for pheochromocytoma. Besides plasma free metanephrines and urine metanephrines, urine or plasma catecholamine tests are also preferred over vanillylmandelic acid testing.

Indications for testing of urine vanillylmandelic acid include the following:

Diagnostic workup of neuroblastoma

Follow-up monitoring in patients treated for neuroblastoma

Foods that can increase urinary catecholamines include the following:

Coffee

Tea

Bananas

Chocolate

Cocoa

Citrus fruits

Vanilla

Drugs that can increase urinary vanillylmandelic acid include the following:

Appetite suppressants

Caffeine

Histamine

Imipramine

Insulin

Epinephrine

Levodopa

Lithium

Morphine

Nitroglycerin

Rauwolfia alkaloids

Isoproterenol

Methocarbamol

Sulfonamide

Chlorpromazine

Drugs that can decrease urine vanillylmandelic acid include the following:

Clonidine

Disulfiram

Guanethidine

MAO inhibitors

Salicylates

Reserpine

Methyldopa

Burris CA, Ashwood ER, Burns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis: Elsevier Saunders; 2006.

McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia: Elsevier Saunders; 2011.

Wallach J. Interpretation of Diagnostic Tests. 9th ed. New York: Little, Brown; 2011.

Test ID: VH Vanillylmandelic Acid (VMA), Pediatric, Urine. Mayo Medical Laboratories. Available at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9254. Accessed: 1/6/2014.

Hanna Lee Florida State University College of Medicine

Disclosure: Nothing to disclose.

Daniel J Van Durme, MD, FAAFP Professor and Chair, Department of Family Medicine and Rural Health, Director, Center of Global Health, Acting Director of Rural Health, Florida State University College of Medicine; Family Physician, Madison County Health Department

Daniel J Van Durme, MD, FAAFP is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, American Public Health Association, Florida Medical Association, Society of Teachers of Family Medicine, Wilderness Medical Society, Physicians for Human Rights, National Rural Health Association, Association for Prevention Teaching and Research, Florida Academy of Family Physicians, World Organization of Family Doctors

Disclosure: Nothing to disclose.

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

Vanillylmandelic Acid (VMA) 

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