Author: Gianpiero Pescarmona
A catecholamine is an organic compound that has a catechol (benzene with two hydroxyl side groups) and a side-chain amine.
Neuroblastoma is the most common extracranial solid cancer in childhood. It arises from any neural crest of simpathetic nervous system.1 Rarely, tumor occur in adolescent age, with an indolent course but a bad prognosis.2
It arise from adrenal ganglia next to spinal cord, mostly in the abdomen, but also in the chest, in the neck or in the pelvis, but, soon, can spread metastases to the bones, bone marrow, liver, lymph nodes, skin and orbits.3
Tumor may present a varied prognosis according to some features, as young age: in patients aged less than 1 year, the tumor may occur in a spontaneous regression or in a benign tumoral evolution (ganglioneuroma) .4; in other cases it may spread quickly .5, especially on bone, since many times bone metastasis are the first tumoral symptom.6.7
Prognosis is affected by local tumoral involvement, metastases, age of the patient, response to treatment and is identified by staging the tumor according to “International Neuroblastoma Staging System” (INSS):.8
Neuroblastoma is a neuroendocrine tumor secreting high levels of catecholamines, so, in about 90% of neuroblastomas, catecholamines metabolites may be found in urine or blood .9, mostly vanillylmandelic acid (VMA). Increased urinary excretion of catecholamines and their metabolites occurs in association with neuroblastoma, so that the detection of VMA clinical value can lead to diagnosis.10
Catecholamine is an organic compound that combines a benzene with two idroxil side groups (1,2 dihydroxybenzene named catechol) and a side chain amine.
In human, the adrenal medulla of the adrenal ganglia release two catecholamines: norepinephrine (noradrenaline) and epinephrine (adrenaline).
These catecholamines originates from phenylalanine and tyrosine. The circulating half-life of these hormones last few minutes, as they are soon degraded in vanilmandelic acid (VMA) and some other molecules (dopamine, metanephrine, normetanephrine, homovanillic acid). Norepinephrine becomes normetanephrine and VMA. Epinephrine becomes metanephrine and VMA. They leave the body through the urine.
vanillylmandelic acid (VMA)
Owing to urinary excretion of catecholamines metabolites, the test is perfomed collecting in a container all the urine for a 24-hours period. In the infant, may be required the use of special adhesive bags on the external genitals.
The test may be affected by some circumstances:
Normal values are:
In infant and child, an elevated urinary level of VMA can be considered a tumoral marker for neuroblastoma (or more rarely for the benign tumor ganglioneuroma).
VMA can be considered a tumoral marker also for pheochromocytoma and rhabdomyosarcoma, but they are tumoral forms developing in adults.11
Diagnosis of neuroblastoma may take a good help by evaluation of VMA urinary level .11 but some authors express the needing of integration with some other clinical and instrumental examination, especially in evaluation of relapse and progression of neuroblastoma .12.13:
The measurement of VMA levels may be necessary for differential diagnosis because bone osteolysis in an infant or a child may often represents the first tumoral symptom in different forms of pediatric tumors (metastasis in neuroblastoma, metastasis of Wilm tumor or Ewing sarcoma), but this abnormal urinary level is a typical results of neuroblastoma.6
Treatment evaluation and the tumor evolution after treatment (surgery, chemotherapy, radiation therapy) are less firmly related to values of VMA urinary level, because tumoral relapse, progression or metastatic spreading can occur without an important urinary VMA elevation.12
In this monitoring, miBG scan is essential for a valid estimation.13
Some trial suggested screening in asymptomatic infants by analysis of urinary VMA levels .14, but some reports demonstrated its uselessness because screening didn’t reduce the number of death due to neuroblastoma, on the contrary it increased number of the diagnosis so that treatment was performed even when the tumor would have disappeared spontaneously.15
Measurement of urinary VMA levels is a simple diagnostic test that confirms the presence of a neuroblastoma in infant or child. It is useful in pediatric diagnosis, especially to differentiate some similar other tumoral forms. In spite of its usefulness, it is as much important to execute more complete clinical investigations in neuroblastoma diagnosis and in assessing evolution or response to treatment.
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