Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma

Abstract Background Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic p...

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Main Authors: Marit F. van denBerg, Hans S. Kooistra, Guy C. M. Grinwis, Sebastiaan A. vanNimwegen, Martijn vanFaassen, Ido P. Kema, Erik Teske, Sara Galac
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Veterinary Internal Medicine
Subjects:
Online Access:https://doi.org/10.1111/jvim.16624
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author Marit F. van denBerg
Hans S. Kooistra
Guy C. M. Grinwis
Sebastiaan A. vanNimwegen
Martijn vanFaassen
Ido P. Kema
Erik Teske
Sara Galac
author_facet Marit F. van denBerg
Hans S. Kooistra
Guy C. M. Grinwis
Sebastiaan A. vanNimwegen
Martijn vanFaassen
Ido P. Kema
Erik Teske
Sara Galac
author_sort Marit F. van denBerg
collection DOAJ
description Abstract Background Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC‐MS/MS between 2018‐2021 were studied retrospectively. Results The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72‐100) and specificity (94%, 95% CI: 79‐99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39‐94) and high specificity (94%, 95% CI: 79‐99). Conclusions and Clinical Importance With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.
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spelling doaj.art-34f712b9282846bdaca4e185e8071eec2023-02-01T04:49:51ZengWileyJournal of Veterinary Internal Medicine0891-66401939-16762023-01-0137117318310.1111/jvim.16624Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytomaMarit F. van denBerg0Hans S. Kooistra1Guy C. M. Grinwis2Sebastiaan A. vanNimwegen3Martijn vanFaassen4Ido P. Kema5Erik Teske6Sara Galac7Department of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsDepartment of Biomolecular Health Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsDepartment of Laboratory Medicine University of Groningen, University Medical Center Groningen Groningen The NetherlandsDepartment of Laboratory Medicine University of Groningen, University Medical Center Groningen Groningen The NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsDepartment of Clinical Sciences, Faculty of Veterinary Medicine Utrecht University Utrecht The NetherlandsAbstract Background Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs). Hypothesis/Objectives To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI). Animals Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs. Methods Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC‐MS/MS between 2018‐2021 were studied retrospectively. Results The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72‐100) and specificity (94%, 95% CI: 79‐99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39‐94) and high specificity (94%, 95% CI: 79‐99). Conclusions and Clinical Importance With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.https://doi.org/10.1111/jvim.16624adrenal tumorcaninecatecholaminesnormetanephrine
spellingShingle Marit F. van denBerg
Hans S. Kooistra
Guy C. M. Grinwis
Sebastiaan A. vanNimwegen
Martijn vanFaassen
Ido P. Kema
Erik Teske
Sara Galac
Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma
Journal of Veterinary Internal Medicine
adrenal tumor
canine
catecholamines
normetanephrine
title Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma
title_full Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma
title_fullStr Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma
title_full_unstemmed Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma
title_short Reference intervals for plasma, urinary, and salivary concentrations of free metanephrines in dogs: Relevance to the diagnosis of pheochromocytoma
title_sort reference intervals for plasma urinary and salivary concentrations of free metanephrines in dogs relevance to the diagnosis of pheochromocytoma
topic adrenal tumor
canine
catecholamines
normetanephrine
url https://doi.org/10.1111/jvim.16624
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