Diagnostic Accuracy of Salivary Metanephrines in Pheochromocytomas and Paragangliomas

Eijkelenkamp, Karin; Osinga, Thamara E.; Faassen, Martijn van; Kema, Ido P.; Kerstens, Michiel N.; Pacák, Karel; Sluiter, Wim J.; Links, Thera P.; Horst-Schrivers, Anouk N A van der

doi:10.1093/clinchem/hvab064

Cited by 3 publications

(7 citation statements)

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“…In humans, metanephrines can be readily measured in saliva of healthy subjects 35 . Recently, it was shown that the diagnostic accuracy of salivary metanephrines was 88%, which makes it a promising tool in the diagnosis of PCC 7 . Theoretically, the use of saliva offers advantages over plasma and urine because samples can be collected easily and noninvasively at home, and collection is minimally stressful.…”

Section: Discussionmentioning

confidence: 99%

“…Measurement of metanephrines and 3MT in plasma, urine and saliva consisted of quantification of free (unconjugated) fractions. At the Department of Laboratory Medicine, concentrations of plasma free and salivary free metanephrines and 3MT were analyzed by an automated LC‐MS/MS method using direct‐matrix derivatization, as previously described and validated for samples from humans 7,22 . Urinary free metanephrines and 3MT were analyzed using essentially the same method as for plasma free metanephrines, but fully validated for human urine.…”

Section: Methodsmentioning

confidence: 99%

“…In humans, biochemical testing for PCC should include measurements of plasma free metanephrines or urinary free metanephrines 6 . Recently, measurement of salivary metanephrines has been shown to be a promising tool in the biochemical diagnosis of PCC in humans 7 . Additionally, measurement of 3‐methoxytyramine (3MT), a metabolite of dopamine, is useful for diagnosis of dopamine‐producing PCCs 8 …”

Section: Introductionmentioning

confidence: 99%

“… 6 Recently, measurement of salivary metanephrines has been shown to be a promising tool in the biochemical diagnosis of PCC in humans. 7 Additionally, measurement of 3‐methoxytyramine (3MT), a metabolite of dopamine, is useful for diagnosis of dopamine‐producing PCCs. 8 …”

Section: Introductionmentioning

confidence: 99%

“…6 Recently, measurement of salivary metanephrines has been shown to be a promising tool in the biochemical diagnosis of PCC in humans. 7 Additionally, measurement of 3-methoxytyramine (3MT), a metabolite of dopamine, is useful for diagnosis of dopamine-producing PCCs. 8 In dogs, routine biochemical testing for PCC only started 10-15 years ago and consists of evaluation of plasma and urinary catecholamines and metanephrines, either by high-pressure liquid chromatography with electrochemical detection (HPLC-ED) [9][10][11][12][13] or by liquid chromatography-tandem mass spectrometry (LC-MS/ MS).…”

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

Berg

Kooistra

Grinwis

et al. 2023

Veterinary Internal Medicne

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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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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Berg

Kooistra

Grinwis

et al. 2023

Veterinary Internal Medicne

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Update on the diagnosis of the pheochromocytoma

Achote,

Arroyo Ripoll,

Araujo-Castro

2024

Hipertensión y Riesgo Vascular

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Biochemical Assessment of Pheochromocytoma and Paraganglioma

2023

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Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the nature of test results, which can also suggest likely size, adrenal versus extra-adrenal location, underlying biology or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.

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Diagnostic Accuracy of Salivary Metanephrines in Pheochromocytomas and Paragangliomas

Cited by 3 publications

References 19 publications

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

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

Update on the diagnosis of the pheochromocytoma

Biochemical Assessment of Pheochromocytoma and Paraganglioma

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