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. 2023 Jan;37(1):173-183.
doi: 10.1111/jvim.16624. Epub 2023 Jan 13.

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

Marit F van den Berg  1 , Hans S Kooistra  1 , Guy C M Grinwis  2 , Sebastiaan A van Nimwegen  1 , Martijn van Faassen  3 , Ido P Kema  3 , Erik Teske  1 , Sara Galac  1
Affiliations

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

Marit F van den Berg et al. J Vet Intern Med. 2023 Jan.

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.

Keywords: adrenal tumor; canine; catecholamines; normetanephrine.

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Conflict of interest statement

Authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Distribution of uNMN/uCr, uMN/uCr, and u3MT/uCr in 37 healthy adult dogs. The y‐axis corresponds with the number of dogs having analyte concentrations reported on the x‐axis. uNMN/uCr, urinary normetanephrine to creatinine ratio; uMN/uCr, urinary metanephrine to creatinine ratio; u3MT/uCr, urinary 3‐methoxytyramine to creatinine ratio
FIGURE 2
FIGURE 2
Plasma NMN, MN, and 3MT directly upon arrival (T0) and after the visit at the hospital (T1) in 37 healthy dogs. pNMN, plasma normetanephrine; pMN, plasma metanephrine; p3MT, plasma 3‐methoxytyramine
FIGURE 3
FIGURE 3
Comparison of (A) plasma normetanephrine (pNMN) concentrations and (B) plasma metanephrine (pMN) concentrations between dogs with pheochromocytoma (PCC) (n = 11), hypercortisolism (HC) (n = 25), and nonadrenal illness (NAI) (n = 6). The box represents the inter quartile range (ie, the second and third quartiles). The line within the box represents the median. The whiskers represent the range, extending to a maximum of 1.5‐times the interquartile range. Outliers are represented by circles above the whiskers. *Statistically significant difference (P < .05) compared to dogs with PCC
FIGURE 4
FIGURE 4
ROC curves to compare the performance of the discriminatory value of pNMN concentration (dashed line) and pMN concentration (solid line) for distinguishing dogs with PCC from dogs with HC and NAI
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