Optimising urinary catecholamine metabolite diagnostics for neuroblastoma
Optimising urinary catecholamine metabolite diagnostics for neuroblastoma
Introduction
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.
Methods
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).
Results
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.
Conclusion
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.
catecholamine metabolites, diagnostic sensitivity, metanephrines, neuroblastoma, tandem mass spectrometry, urine collection
Gray, Juliet
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Matser, Yvette A.H.
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Verly, Iedan R.N.
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van der Ham, Maria
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de Sain-van der Velden, Monique G.M.
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Verhoeven-Duif, Nanda M.
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Ash, Shifra
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Cangemi, Giuliana
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Barco, Sebastiano
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Popovic, Maja Beck
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van Kuilenburg, Andre B.P.
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Tytgat, Godelieve A.M.
cedac06c-44d2-483c-9d32-9430b8047eb8
June 2023
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
Matser, Yvette A.H.
3fc564a9-0e22-4030-a7ef-6ccf39c6e596
Verly, Iedan R.N.
89cf342a-c592-4849-a061-56306eda41f4
van der Ham, Maria
2f2d83dc-89b3-4467-aa68-25cb1a701f72
de Sain-van der Velden, Monique G.M.
97155518-3909-4bf1-a865-cda130461c68
Verhoeven-Duif, Nanda M.
0b54ac1f-9957-485b-89c7-315a6d1b8621
Ash, Shifra
8d6ba9cd-b9bb-448d-9800-c93e8ca31ca3
Cangemi, Giuliana
f9e145bf-9137-4c62-aee2-bca6464d61ce
Barco, Sebastiano
c36743c7-4ec9-4916-b3dd-726c0f020203
Popovic, Maja Beck
6093b66e-176f-47a9-96df-a76c64b5d9cb
van Kuilenburg, Andre B.P.
91502f88-e0d5-41df-88b7-88d67a0d235f
Tytgat, Godelieve A.M.
cedac06c-44d2-483c-9d32-9430b8047eb8
Gray, Juliet, Matser, Yvette A.H., Verly, Iedan R.N., van der Ham, Maria, de Sain-van der Velden, Monique G.M., Verhoeven-Duif, Nanda M., Ash, Shifra, Cangemi, Giuliana, Barco, Sebastiano, Popovic, Maja Beck, van Kuilenburg, Andre B.P. and Tytgat, Godelieve A.M.
(2023)
Optimising urinary catecholamine metabolite diagnostics for neuroblastoma.
Pediatric Blood and Cancer, 70 (6), [e30289].
(doi:10.1002/pbc.30289).
Abstract
Introduction
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.
Methods
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).
Results
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.
Conclusion
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.
Text
Pediatric Blood Cancer - 2023 - Matser - Optimising urinary catecholamine metabolite diagnostics for neuroblastoma (1)
- Version of Record
More information
Accepted/In Press date: 20 February 2023
Published date: June 2023
Additional Information:
Funding Information:
This work was supported by a grant from the Villa Joep Foundation.
Publisher Copyright:
© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.
Keywords:
catecholamine metabolites, diagnostic sensitivity, metanephrines, neuroblastoma, tandem mass spectrometry, urine collection
Identifiers
Local EPrints ID: 476058
URI: http://eprints.soton.ac.uk/id/eprint/476058
ISSN: 1545-5017
PURE UUID: 5707d5e3-8e28-4405-beec-51fc8d71ef22
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Date deposited: 04 Apr 2023 17:08
Last modified: 17 Mar 2024 02:57
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Contributors
Author:
Yvette A.H. Matser
Author:
Iedan R.N. Verly
Author:
Maria van der Ham
Author:
Monique G.M. de Sain-van der Velden
Author:
Nanda M. Verhoeven-Duif
Author:
Shifra Ash
Author:
Giuliana Cangemi
Author:
Sebastiano Barco
Author:
Maja Beck Popovic
Author:
Andre B.P. van Kuilenburg
Author:
Godelieve A.M. Tytgat
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