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. 2021 Aug 5;67(8):1090-1097.
doi: 10.1093/clinchem/hvab064.

Diagnostic Accuracy of Salivary Metanephrines in Pheochromocytomas and Paragangliomas

Karin Eijkelenkamp  1 , Thamara E Osinga  1 , Martijn van Faassen  2 , Ido P Kema  2 , Michiel N Kerstens  1 , Karel Pacak  3 , Wim J Sluiter  1 , Thera P Links  1 , Anouk N A van der Horst-Schrivers  1   4
Affiliations

Diagnostic Accuracy of Salivary Metanephrines in Pheochromocytomas and Paragangliomas

Karin Eijkelenkamp et al. Clin Chem. .

Erratum in

Abstract

Background: Measurements of plasma free metanephrines are recommended for diagnosing pheochromocytomas and paragangliomas (PPGL). Metanephrines can be detected in saliva with LC-MS/MS with sufficient analytical sensitivity and precision. Because collecting saliva is noninvasive and less cumbersome than plasma or urine sampling, we assessed the diagnostic accuracy of salivary metanephrines in diagnosing PPGL.

Methods: This 2-center study included 118 healthy participants (44 men; mean age: 33 years (range: 19--74 years)), 44 patients with PPGL, and 54 patients suspected of PPGL. Metanephrines were quantified in plasma and saliva using LC-MS/MS. Diagnostic accuracy; correlation between plasma and salivary metanephrines; and potential factors influencing salivary metanephrines, including age, sex, and posture during sampling, were assessed.

Results: Salivary metanephrines were significantly higher in patients with PPGL compared with healthy participants (metanephrine (MN): 0.19 vs 0.09 nmol/L, P < 0.001; normetanephrine (NMN): 2.90 vs 0.49 nmol/L, P < 0.001). The diagnostic sensitivity and specificity of salivary metanephrines were 89% and 87%, respectively. Diagnostic accuracy of salivary metanephrines was 88%, with an area under the ROC curve of 0.880. We found a significant correlation between plasma and salivary metanephrines (Pearson correlation coefficient: MN, 0.86, P < 0.001; NMN, 0.83, P < 0.001). Salivary NMN concentrations were higher when collected in a seated position compared with supine (P < 0.001) and increased with age (P < 0.001).

Conclusions: Salivary metanephrines are a promising tool in the biochemical diagnosis of PPGL. Salivary metanephrines correlate with plasma free metanephrines and are increased in patients with PPGL. At this time, however, salivary metanephrines cannot replace measurement of plasma free metanephrines.

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Figures

Fig. 1.
Fig. 1.
Flowchart of the inclusion of healthy participants, patients with PPGL, and patients with suspected PPGL.
Fig. 2.
Fig. 2.
Concentrations (median and IQR) of salivary MN (A) and NMN (B) in patients with PPGL, patients with suspected PPGL, and healthy participants. The dotted line shows the upper reference limit of salivary MN (0.25 nmol/L) and NMN (1.46 nmol/L).
Fig. 3.
Fig. 3.
Correlation between salivary and plasma MN (A) and NMN (B) concentrations.
Fig. 4.
Fig. 4.
ROC curve for salivary and plasma metanephrines in the supine position, constructed according to logistic regression model with a combination of NMN and MN, including patients with PPGL and patients with suspected PPGL in whom PPGL was excluded. AUC, area under the curve.
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