Comparative values of catecholamines and metabolites for the diagnosis of neuroblastoma

Abstract

In order to diagnose neuroblastomas, we assayed the three adrenal hormones and five of their metabolites by high-performance liquid chromatography followed by electrochemical detection in urine samples of 395 children with tumours of unknown nature (including 29 neuroblastomas). The analytes (expressed as analyte/ creatinine ratios) performances were determined by calculating the related sensitivity and specificity and receiver operating characteristics curves within the different age groups. Normetanephrine (NME), vanillylmandelic and homovanillic acids (VMA, HVA) were the best analytes. Calculated optimal thresholds (best specificity/sensitivity couples) of these analytes minimised the number of falsepositive diagnosis. Conclusion: combined determination of normetanephrine with vanillylmandelic acid (0-1 year) or homovanillic acid (1-5 years and 5-10 years) further enhanced the diagnostic power up to 100% sensitivity and specificity of the testing depending on the age group. Plotting individual levels (normetanephrine versus vanillylmandelic acid or homovanillic acid) allowed a rapid visual analysis that would have missed only one small low grade non-secreting tumour. Keywords Urinary catecholamines AE NeuroblastomaAbbreviations DA dopamine AE HPLC/ED high performance liquid chromatography with electrochemical detection AE HVA homovanillinic acid AE MDA methoxydopamine AE ME metanephrine AE NME normetanephrine AE ROC receiver operating characteristic AE VMA vanillylmandelic acid Eur

Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: Relevance to the diagnosis of neuroblastoma

“…Moreover, muscular mass, disease state, and drugs further alter creatinine excretion. For instance, the compilation of four recently published reference intervals and our own data using HPLC with electrochemical detection for NE, DA, VMA, and HVA in children <1 year of age illustrates this variability indicating upper reference limits at respectively <75, 73, 130, 140 and 280 nmol/mmol creatinine for NE; at 1104, 1428, 1500, 1500 and 1600 nmol/mmol creatinine for DA; at 10, 12, 14, 14 and 30 mmol/mmol creatinine for VMA; at 20, 20, 20, 23 and 32 mmol/mmol creatinine for HVA [8,9,22,23]. The high sensitivity of plasma free metanephrines observed in our work, which has also been established for the diagnosis of pheochromocytoma, may be attributed to the expression of catechol-O-methyl transferase by neuroblastoma.…”

Prognostic value of ferritin, neuron-specific enolase, lactate dehydrogenase, and urinary and plasmatic catecholamine metabolites in children with neuroblastoma

“…LDH, NSE, and ferritin were determined on heparinized plasma, using routine clinical chemistry laboratory methods. Sensitivity and specificity of urinary HVA and VMA are reported in Monsaingeon et al13; sensitivity of plasma HVA, VMA, NSE, and LDH in Simon et al14; specificity of NSE in Viallard et al15; whereas ferritin and LDH are nonspecific markers.…”

Urinary sampling for 5HIAA and metanephrines determination: revisiting the recommendations

“…To biologically diagnose pheochromocytomas or paragangliomas or neuroblastomas, various tumour-related markers might be assayed (72, 73, 74). Because these tumoural cells are from the same origin as the medullary adrenal, they may also secrete catecholamines and/or their methoxylated metabolites, a.k.a.…”