Princess Máxima Centre for Paediatric Oncology, Utrecht, The Netherlands.
Laboratory of Genetic Metabolic Diseases, Amsterdam UMC University of Amsterdam, Amsterdam, The Netherlands.
Pediatr Blood Cancer. 2023 Jun;70(6):e30289. doi: 10.1002/pbc.30289. Epub 2023 Apr 3.
The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma.
Twenty-four-hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FD) and/or ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS).
Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24-hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24-hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver-operating-characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods.
Catecholamine metabolites in spot urine and 24-hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.
尿儿茶酚胺代谢物分析是神经母细胞瘤诊断的基石。目前，关于采样方法尚无共识，并且儿茶酚胺代谢物的组合也各不相同。我们研究了是否可以使用随机尿样可靠地分析用于诊断神经母细胞瘤的儿茶酚胺代谢物。
在诊断时收集了患有和未患有神经母细胞瘤的患者的 24 小时尿液或随机尿液样本。通过高效液相色谱法与荧光检测（HPLC-FD）和/或超高效液相色谱法与电喷雾串联质谱法（UPLC-MS/MS）测量高香草酸（HVA）、香草扁桃酸（VMA）、多巴胺、3-甲氧基酪胺、去甲肾上腺素、变肾上腺素、肾上腺素和间甲肾上腺素。
在 400 名神经母细胞瘤患者（24 小时尿液，n = 234；随机尿液，n = 166）和 571 名对照者（均为随机尿液）的尿液样本中测量了儿茶酚胺代谢物水平。在 24 小时尿液和随机尿液样本中，儿茶酚胺代谢物的排泄水平和每种代谢物的诊断敏感性相似（所有代谢物的 p >.08 和 >.27）。包含所有八种儿茶酚胺代谢物的代谢物组的曲线下面积（AUC）明显高于仅 HVA 和 VMA 的 AUC（AUC = 0.952 对 0.920，p =.02）。两种分析方法之间未观察到代谢物水平的差异。
随机尿和 24 小时尿液中的儿茶酚胺代谢物产生了相似的诊断敏感性。儿茶酚胺工作组建议将随机尿液作为标准护理。八种儿茶酚胺代谢物的组合比 VMA 和 HVA 具有更高的诊断准确性。
