Urinary Cathecolamines
Urine Tests

Author: Gianpiero Pescarmona
Date: 12/07/2012


A catecholamine is an organic compound that has a catechol (benzene with two hydroxyl side groups) and a side-chain amine.


2012-07-12T13:23:05 - Annamaria Ruggieri

Urynary excretion of cathecolamines in association with neuroblastoma

di Annamaria Ruggieri


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

StageI : Tumour confined to organ or structure of origin

StageII : Tumour extending in continuity beyond the organ or structure of origin but not crossing the midline. Regional lymph nodes on the homolateral side may be involved

StageIII : Tumours extending in continuity beyond the midline. Regional lymph modes may be involved bilaterally

StageIV : Remote disease involving skeleton, organs, soft tissues, or distant lymph nodes

StageIVs: Patients who would otherwise be stage I or II, but who have remote disease confined only to one or more of the following sites: liver, skin, or bone marrow (without radiographic evidence of bone metastases on complete skeletal survey)

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).

norepinephrine (noradrenaline)

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)

norepinephrine catabolism


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:

  • Anxiety, stress and vigorous physical exercises may elevate measurements
  • Some food can increase urinary catecholamines: coffee, tea, bananas, cocoa, citrus fruits, vanilla
  • Drugs can affect test results
    • by elevating measurements (alcohol, aminophylline, amphetamines, buspirone, caffeine, cocaine, phenylephrine, pseudoephedrine, levodopa, methyldopa, phenothiazines, reserpine, tricyclic antidepressants)
    • or by decreasing them (clonidine, disulfiram, guanetidine, MAO inhibitors, salicylates)

Normal values are:

  • VMA: 2-7 mg/24 hours
  • Total urine catecholamines: 14-110/24 hours


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:

  1. Signs and symptoms are general (fatigue, loss of appetite, fever) or related to tumor location or metastases in the abdomen (swollen belly, constipation), in the chest (breathing disease), on the spinal cord (trouble in limb movements), in the bone (leg or hip pain), in the bone marrow (anemia, pallor);
  2. CT or MRI scan of the abdomen or of the chest can explore the tumoral local diffusion;
  3. miBG (meta-iodobenzylguanidine) scintigraphy and total bone scintigraphy can display metastases;
  4. Biopsy of the tumor and bone marrow biopsy analyze histological and cellular patterns.

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.


1 eMedicine - Neuroblastoma : Article by Norman J Lacayo, MD . Retrieved 2008-07-30

2 Conte M, Parodi S, De Bernardi B et al (2006) “Neuroblastoma in Adolescents. The Italian Experience” Cancer 106 (6): 1410-17 PMID: 16475209

3 A.D.A.M. Medical Encyclopedia – Neuroblastoma : Article by Yi-Bin Chen, David Zieve, http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002381/

4 Bénard J, Raguénez G, Kauffmann A, et al. (October 2008). "MYCN-non-amplified metastatic neuroblastoma with good prognosis and spontaneous regression: a molecular portrait of stage 4S". Mol Oncol 2 (3): 261–71. PMID 19383347

5 Neuroblastoma: Pediatric Cancers: - Merck Manual Professional . Retrieved 2008-01-01

6 Boriani S, Govoni E, Ruggieri P, Biagini R, Severi B (1985) “Bone metastases of neuroblastoma: the role of the orthopaedic surgeon.” Ital J Orthop Traumatol 11(3) : 355-63. PMID: 4086282

7 Campanacci M (1981) “Metastasi ossee da neuroblastoma” in “Tumori delle ossa e delle parti molli” Aulo Gaggi Editore – Bologna: 571-6

8 Evans, A. E., D'Angio, G. J., and Randolph, J. (1971b). “A proposed staging for children with neuroblastoma.” Cancer, 27, 374-8. PMID: 5100400

9 Strenger V, Kerbl R, Dornbusch HJ, et al. (2007). "Diagnostic and prognostic impact of urinary catecholamines in neuroblastoma patients". Pediatr Blood Cancer 48 (5): 504–9. PMID 16732582

10 Bond JV (1975) “Clinical significance of catecholamine excretion levels in diagnosis and treatment of neuroblastoma.” Arch Dis Child 50(9):691-5 PMID: 1190818

11 Vachani C (2006) “Patient Guide to Tumor Markers” Oncolink – Abramson Cancer Center of the University of Pennsylvania http://www.oncolink.org/treatment/article.cfm?id=296&s=42&c=7

12 Kusher B H, Kramer K, Modak S et al (2009) “Sensitivity of Surveillance Studies for Detecting.Asymptomatic and Unsuspected Relapse of High-Risk Neuroblastoma” J Clin Oncol 27 (7) : 1041-6 PMID:19171710

13 Simon T, Hero B, Hunneman DH, Berthold F (2003) “Tumour markers are poor predictors for relapse or progression in neuroblastoma” Eur J Cancer 39(13):1899-903 PMID: 12932669

14 Woods WG, Gao RN, Shuster JJ, et al. (2002). "Screening of infants and mortality due to neuroblastoma". N. Engl. J. Med. 346 (14): 1041–6. PMID 11932470

15 Tsubono Y, Hisamichi S (2004). "A halt to neuroblastoma screening in Japan". N. Engl. J. Med. 350 (19): 2010–1. PMID 15128908 .

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