Homovanillic acid (HVA) and vanillilmandelic acid (VMA)

The article was written by Doctor Le Duy Cuong - Biochemistry Unit - Laboratory Department - Vinmec Times City International General Hospital.

The determination of VMA and HVA in urine is used in the screening of catecholamine-secreting tumors in children such as neuroblastoma (neuroblastoma), pheochromocytoma, various types of neural crest tumors as well as in monitor the effectiveness of treatment for these tumors.

Increased levels of HVA, VMA and catecholamine metabolites may be suggestive of the occurrence of catecholamine-secreting tumors. The detection of urinary HVA and VMA secretion in neuroblastoma is well known. HVA and VMA levels are elevated in 90% of patients with neuroblastoma, so both tests should be ordered when in doubt.

Neuroblastoma is the most common intra-abdominal malignancy in children, with an annual incidence of about 6-10/1 million children, and is the third most common malignancy in children after Leucemia and glioma. These tumors develop from primitive (immature) neurons of the sympathetic nervous system, so they are often found in the adrenal medulla and in the sympathetic ganglia. Neuroblastoma is common in children under 5 years of age, of which up to 30% occurs in children under 1 year of age. Only 5% are found in children over 10 years old.
Neuroblastoma can appear in nerve tissue in the neck, chest, or around the spinal cord. Pediatric patients should have VMA and HVA levels checked during treatment and follow-up after treatment to assess the effectiveness of the regimen as well as the possibility of tumor recurrence. Concentrations of these substances will decrease as the patient responds well to treatment. Therefore, HVA and VMA are known as neuroblastoma tumor markers.

VMA is a more sensitive marker in the early stages of neuroblastoma while HVA is more sensitive when the tumor is already in the clear stage. The sensitivity of HVA and VMA in the diagnosis of neuroblastoma depends on the stage of the disease, increasing gradually as the disease is advanced. Stages I and II are 66 and 63% respectively, stage III 78%, stage IV and IV S 90 and 98% respectively.

One reason for a false-negative result in the early stages of the disease is the endocrine inactivation of the tumor by tyrosine hydroxylase enzyme deficiency. Furthermore, small tumors are also difficult to detect because catecholamine secretion is increased only when the tumor reaches approximately 5 grams in weight. That's also why there are neuroblastomas that are already diagnosed in stages III and IV.
In pheochromocytoma, > 90% of cases have elevated VMA, if both VMA and metanephrine are elevated, > 98% have pheochromocytoma. Meanwhile, in neuroblastoma, elevations of norepinephrine and normetanephrine are uncommon.

The specimen used to quantify HVA and VMA is urine. A midstream urine sample may be randomly collected or a 24-hour urine collection (record total volume collected over 24 hours). Correct urine pH to about 1-5 with HCl or acetic acid.
Patients treated with L-dopa, Bactrim may affect the results of HVA and VMA quantification, therefore patients should be discontinued 24 hours before sampling.
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