Vanillylmandelic Acid (VMA)

Updated: Sep 28, 2020
Author: Hanna Lee; Chief Editor: Eric B Staros, MD 

Reference Range

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

Normal findings[1]

  • Adult/elderly: < 6.8 mg/24 hr or < 35 μmol/24 hr (SI units)
  • Adolescent: 1-5 mg/24 hr
  • Child: 1-3 mg/24 hr
  • Infant: < 2 mg/24 hr
  • Newborn: < 1 mg/24 hr
 

Interpretation

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

  • Neuroblastoma

  • Pheochromocytoma

  • Other neural crest tumors (eg, ganglioblastoma, ganglioneuroma)

  • Severe anxiety/stress

 

Collection and Panels

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)

 

Background

Description

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/Applications

Indications for testing of urine vanillylmandelic acid include the following:

  • Diagnostic workup of neuroblastoma

  • Follow-up monitoring in patients treated for neuroblastoma

Considerations

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