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Test ID VMA Vanillylmandelic Acid, 24 Hour, Urine

Reporting Name

Vanillylmandelic Acid, 24 Hr, U

Useful For

Screening children for catecholamine-secreting tumors using a 24-hour urine collection when requesting testing for vanillylmandelic acidonly

 

Supporting a diagnosis of neuroblastoma

 

Monitoring patients with a treated neuroblastoma

Specimen Type

Urine


Ordering Guidance


In the past, this test has been used to screen for pheochromocytoma. However, vanillylmandelic acid (VMA) is not the analyte of choice to rule out a diagnosis of pheochromocytoma. Recommended tests for that purpose include:

-PMET / Metanephrines, Fractionated, Free, Plasma

-METAF / Metanephrines, Fractionated, 24 Hour, Urine

-CATU / Catecholamine Fractionation, Free, 24 Hour, Urine



Necessary Information


1. Patients age is required.

2. Collection duration (in hours) and urine volume (in milliliters) are required.

3. All patients receiving L-dopa should be identified to the laboratory when this test is ordered.

4. Bactrim may interfere with detection of the analyte. All patients taking Bactrim should be identified to the laboratory when this test is ordered.



Specimen Required


Patient Preparation: Administration of L-dopa may falsely-increase vanillylmandelic acid results; it should be discontinued 24 hours prior to and during specimen collection.

Supplies: Urine Tubes, 10 mL (T068)

Collection Container/Tube: Clean, plastic urine collection container

Submission Container/Tube: Plastic, 10-mL urine tube

Specimen Volume: 5 mL

Collection Instructions:

1. Add 25 mL of 50% acetic acid as preservative at the start of collection. If specimen is refrigerated during collection, preservative may be added up to 12 hours after collection. Use 15 mL of 50% acetic acid for children younger than 5 years. This preservative is intended to achieve a pH of between approximately 1 and 5.

2. Collect a 24-hour urine specimen.

3. If necessary, adjust urine pH to a level between 1 and 5 by adding 50% acetic acid or hydrochloric acid dropwise and checking the pH.

Additional Information: For multiple collections see Urine Preservatives-Collection and Transportation for 24-Hour Urine Specimens.


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Urine Refrigerated (preferred) 28 days
  Frozen  180 days

Reference Values

<1 year: <25.0 mg/g creatinine

1 year: <22.5 mg/g creatinine

2-4 years: <16.0 mg/g creatinine

5-9 years: <12.0 mg/g creatinine

10-14 years: <8.0 mg/g creatinine

≥15 years (adults): <8.0 mg/24 hours

Day(s) Performed

Monday through Friday

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

84585

Clinical Information

Vanillylmandelic acid (VMA) and other catecholamine metabolites (homovanillic acid [HVA] and dopamine) are typically elevated in patients with catecholamine-secreting tumors (eg, neuroblastoma, pheochromocytoma, and other neural crest tumors). VMA and HVA levels may also be useful in monitoring patients who have been treated as a result of one of the above-mentioned tumors.

Interpretation

Vanillylmandelic acid and/or homovanillic acid concentrations are elevated in most patients (more than 90%) with neuroblastoma; both tests should be performed. A positive test could be due to a genetic or nongenetic condition. Additional confirmatory testing is required.

 

A normal result does not exclude the presence of a catecholamine-secreting tumor.

 

Elevated values are suggestive of a pheochromocytoma, but they are not diagnostic.

Cautions

Values are more commonly elevated during a hypertensive episode.

 

Values may be normal in some individuals with pheochromocytoma.

 

All patients taking Bactrim should be identified to the laboratory when vanillylmandelic acid and homovanillic acid tests are ordered due to potential interference.

Clinical Reference

1. Eisenhofer G. Monoamine-producing tumors. In: Rifai N, Chiu RWK, Young I, Burnham CD, Wittwer CT, eds. Tietz Textbook of Laboratory Medicine. 7th ed. Elsevier; 2023: 765-765.e54

2. Hyland K. Disorders of neurotransmitter metabolism. In: Blau N, Duran M, Blaskovics ME, Gibson KM, eds. Physician's Guide to the Laboratory Diagnosis of Metabolic Diseases. Springer; 2003:107-122

3. Ormazabal A. Molero-Luis M. Garcia-Cazorla A. Artuch R. Biomarkers for the study of catecholamine and serotonin genetic diseases. In: Garg U, Smith LD, eds. Biomarkers in Inborn Errors of Metabolism: Clinical Aspects and Laboratory Determination. Elsevier; 2017:301-329

4. Strenger V, Kerbl R, Dornbusch HJ, et al. Diagnostic and prognostic impact of urinary catecholamines in neuroblastoma patients. Pediatr Blood Cancer. 2007;48(5):504-509

5. Barco S, Gennai I, Reggiardo G, et al. Urinary homovanillic and vanillylmandelic acid in the diagnosis of neuroblastoma: report from the Italian Cooperative Group for Neuroblastoma. Clin Biochem. 2014;47(9):848-852

6. Matthay KK, Maris JM, Schleiermacher G, et al. Neuroblastoma. Nat Rev Dis Primers. 2016;2:16078. doi:10.1038/nrdp.2016.78

Method Description

Vanillylmandelic acid (VMA) is measured by solid-phase extraction (SPE) of a 1-mL aliquot of urine. A known amount of stable-isotope labeled VMA internal standard (IS) is added to each urine specimen prior to SPE. VMA and IS are eluted from the SPE column with methanol. The methanol is evaporated and the VMA and IS are redissolved in liquid chromatography tandem mass spectrometry mobile phase. A portion of this prepared extract is injected onto a LC column that separates VMA and IS from the bulk of any remaining specimen matrix. The VMA and IS are measured by tandem-mass spectrometry using the selected reaction monitoring mode. VMA is quantified using the ratio to IS versus urine calibrators.(Magera MJ, Thompson AL, Stoor AL, et al. Determination of vanillylmandelic acid in urine by stable isotope dilution and electrospray tandem mass spectrometry. Clin Chem. 2003;49:825-826; Eisenhofer G, Grebe S, Cheung NV. Monoamine-producing tumors. In Rifai N, Horvath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018:chap 63)

Report Available

3 to 5 days

Reject Due To

  All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

NY State Approved

Yes

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

Highlights

Vanillylmandelic acid (VMA) and other catecholamine metabolite, such as homovanillic acid (HVA), measurements in urine are used for screening children for catecholamine-secreting tumors, such as neuroblastoma and other neural crest tumors, and monitoring those who have had treatment for these tumors.

 

More than 90% of individuals with neuroblastoma have elevated VMA and/or HVA.

 

VMA is not the analyte of choice for diagnosis of pheochromocytoma, which is better detected by testing for metanephrines.

 

Treatment with L-dopa can impact test results and should be discontinued 24 hours prior to collection. Bactrim can impact test results and should be noted at time of collection.

Urine Preservative Collection Options

Note: For addition of preservative or application of temperature information, see Specimen Required.

Ambient (No additive)

No

Refrigerate (No additive)

No

Frozen (No additive)

No

50% Acetic Acid

Preferred

Boric Acid*

OK

Diazolidinyl Urea

No

6M Hydrochloric Acid

OK

6M Nitric Acid

OK

Sodium Carbonate

No

Thymol

No

Toluene

No

*If boric acid is used, note on specimen container. Also, verify that pH is in desired range (pH=1-5). If pH is outside of desired range, adjust pH with a stronger acid (acetic acid is preferred but other acids listed above could be used if available) in a dropwise fashion to bring pH into desired range.

Forms

If not ordering electronically, complete, print, and send an Oncology Test Request (T729) with the specimen.