Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

Sawka, Anna M.; Thabane, Lehana; Gafni, Amiram; Levine, Mitchell; Young, William F.

doi:10.1186/1472-6823-5-1

Cited by 40 publications

(31 citation statements)

References 19 publications

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“…It confirms, if needed, that urine assays are sound methods for this purpose (8,10,11,12,13,15,17,18,20). This study also confirms a clear usefulness of plasma assays in a major clinical centre as already demonstrated (10,11,12,13,15,17,18).…”

Section: Discussionsupporting

confidence: 69%

“…The ROC AUC of our data are in general agreement with others' publications both in terms of AUC and ranked performance of the analytes (11,15,21,22). On the other hand, the sensitivities and specificities linked to given concentrations may differ in the various publications including this one.…”

Section: Laboratory Considerationssupporting

confidence: 79%

“…Since then, assays of pNMA and pMA have indeed clearly demonstrated a great potential for the diagnosis of phaeochromocytomas and paragangliomas (10,11,12,13,14,15,16,17,18). We present the set-up of these assays in 2005, their analytical performances and the main consequences of their routine use in our laboratory.…”

Section: Introductionmentioning

confidence: 99%

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Phasing-in plasma metanephrines determination

Brossaud¹,

Gosse²,

Gatta³

et al. 2013

European Journal of Endocrinology

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Objectives: We set up plasma normetanephrine (pNMA) and metanephrine (pMA) assays as they demonstrated their usefulness for diagnosing phaeochromocytomas. Our scope is to describe some practical laboratory aspects and the clinical relevance of these assays in our endocrinological or cardiological departments. Methods: We retrospectively reviewed the results of MA from a population of in-and outpatients over a 7-year period. Subjects (nZ2536) from endocrinological or cardiological departments were investigated (66 phaeochromocytomas). Urinary NMA (uNMA) and pNMA, and urinary MA (uMA) and pMA were assayed by HPLC with electrochemical detection. Results: pNMA and pMA assays are now more frequently requested than uNMA and uMA. This changed our laboratory work load with improved delivery, sensitivity and reliability of plasma assays as well as reduced apparatus maintenance time. The pNMA and pMA upper reference limits (URLs) of subjects with no phaeochromocytoma were 1040 and 430 pmol/l respectively. Sensitivity and specificity based on receiver operating characteristic curves optimal points were 83 and 93% for pNMA at 972 pmol/l and 67 and 98% for pMA at 638 pmol/l. Sensitivity and specificity of paired tests of pMA (positive test: at least one analyte above its URLs) were 100 and 91% respectively. Conclusion: The very low concentration of analytes requires a sustained very good apparatus analytical sensitivity. This can be obtained in an up-to-date laboratory. In terms of clinical performances, assays in plasma or urine are equivalent. Depending on local preferences, populations, strategies or departments, requests for one or the other assay may sustain the need for specifically defined reference ranges.

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Section: Discussionsupporting

confidence: 69%

Section: Laboratory Considerationssupporting

confidence: 79%

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Phasing-in plasma metanephrines determination

Brossaud¹,

Gosse²,

Gatta³

et al. 2013

European Journal of Endocrinology

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“…Since plasma concentrations of normetanephrine increase with advancing age (34 ), use of age-adjusted reference intervals has been proposed to minimize falsepositive results (35 ). As outlined in a subsequent study, such optimization, with a diagnostic specificity reaching 96%, can be achieved from an age adjustment for the upper cutoffs for plasma normetanephrine (36 ).…”

Section: Reference Intervalsmentioning

confidence: 99%

Laboratory Evaluation of Pheochromocytoma and Paraganglioma

Eisenhofer

Peitzsch²

2014

Clinical Chemistry

156

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BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are potentially lethal yet usually surgically curable causes of endocrine hypertension; therefore, once clinical suspicion is aroused it is imperative that clinicians choose the most appropriate laboratory tests to identify the tumors. CONTENT:Compelling evidence now indicates that initial screening for PPGLs should include measurements of plasma free metanephrines or urine fractionated metanephrines. LC-MS/MS offers numerous advantages over other analytical methods and is the method of choice when measurements include methoxytyramine, the O-methylated metabolite of dopamine. The plasma test offers advantages over the urine test, although it is rarely implemented correctly, rendering the urine test preferable for mainstream use. To ensure optimum diagnostic sensitivity for the plasma test, reference intervals must be established for blood samples collected after 30 min of supine rest and after an overnight fast when measurements include methoxytyramine. Similarly collected blood samples during screening, together with use of age-adjusted reference intervals, further minimize false-positive results. Extents and patterns of increases in plasma normetanephrine, metanephrine, and methoxytyramine can additionally help predict size and adrenal vs extraadrenal locations of tumors, as well as presence of metastases and underlying germline mutations of tumor susceptibility genes.

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“…Our goal was to reassess the stability in urine of both unconjugated free and methylated compounds, over a pH range of 2.0, 4.0, 6.0 and 8.0, temperatures of -18 o C, 4 o C and room temperature (20)(21)(22)(23)(24)(25)(26) o C), and over a long period of time (days up to 10 weeks). We chose a reference urine material so that we could be certain of the concentrations (added in as the free metabolites) and little variation in antioxidants such as vitamin C that could affect stability.…”

Section: Introductionmentioning

confidence: 99%

A study on the stability of urinary free catecholamines and free methyl-derivatives at different pH, temperature and time of storage

Roberts

Higgins

Sargazi

2009

Clinical Chemistry and Laboratory Medicine

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Bakground: The goal of our study was to test the relative stability of urine, unconjugated, free catecholamines and the methyl derivatives. We measured the change in concentrations in commercially available urines after storage at various pH values, temperatures and time, from days up to 10 weeks. Methods: Samples of commercial control urines were adjusted to pH 2.0, 4.0, 6.0 and 8.0 and aliquots stored at ambient temperature (20-268C), 48C and -18 o C. The free catecholamines (cats) and the free methyl derivatives (mets) were measured after 1, 2, 3 and 6 days and 1, 2, 3 and 10 weeks using the automated sample trace enrichment dialysis (ASTED) procedure with reversed phase ion pair high performance liquid chromatography (HPLC) and coulometric detection. Results: Free catecholamines were relatively stable, with -15% loss of concentration, when stored at pH 6.0 or less for at least 4 days and up to 10 weeks at pH 2.0 at either 4 o C or -18 o C. At pH 8.0, the concentration fell to -60% after 48 h and at a pH of 6.0 or 8.0, up to 90% was lost within the first week at 4 o C and 25 o C. More than 40% of free normetadrenaline and metadrenaline were lost after 1-2 weeks when stored at 20-25 o C and pH 8.0. After 10 weeks at pH 4.0, 6.0 and 8.0, up to 90% loss was observed at 25 o C. Free cats were stable at pH 2.0 and 4.0 at -18 o C and the free mets were stable at -18 o C over the entire time period studied and at all pHs. Conclusions: In the analysis of free catecholamine and the free methyl derivatives, urine samples should be acidified to a pH range 2.0-3.0 to ensure stability and hence the correct analysis.

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Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

Cited by 40 publications

References 19 publications

Phasing-in plasma metanephrines determination

Phasing-in plasma metanephrines determination

Laboratory Evaluation of Pheochromocytoma and Paraganglioma

A study on the stability of urinary free catecholamines and free methyl-derivatives at different pH, temperature and time of storage

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