Diagnostic accuracy of free and total metanephrines in plasma and fractionated metanephrines in urine of patients with pheochromocytoma.
BACKGROUND
Plasma free and urinary metanephrines are recognized biomarkers for the assessment of pheochromocytoma. Plasma total metanephrines with a long half-life may represent another useful biomarker.


OBJECTIVE
The aim of this study is to evaluate the diagnostic performances of plasma total metanephrines alone or combined with free metanephrines and fractionated 24-h urinary metanephrines.


METHODS
A retrospective, case-control diagnostic test study was conducted between 1999 and 2007 in two university hospitals in Switzerland and two institutions in France. The patients included 46 cases with histologically proven pheochromocytoma, and 181 controls suspected of tumor with negative investigations and 3-year follow-up. None had renal dysfunction. Sensitivity and specificity were compared after expressing each measurement result as a ratio over its upper reference limit, adding the ratios of normetanephrine and metanephrine, and defining cut-off values of 1 or 2 for this sum.


RESULTS
Applying a cut-off value of 1, plasma free and total metanephrines and urinary fractionated metanephrines had similar sensitivities of 96% (95% confidence interval, 86-99%), 95% (85-99%), and 95% (84-99%) along with similar specificities of 89% (83-94%), 91% (84-95%), and 86% (80-91%). A cut-off of 2 for the sum of ratios over reference limit improves the specificity, and it can be used for a confirmation test based on another biomarker taken among the three biomarkers.


CONCLUSIONS
All three metanephrine-based tests perform equivalently for diagnosing pheochromocytoma in the absence of renal insufficiency, and can be conveniently associated two by two for confirming/excluding tumor.
Grouzmann
Eric
E
Division of Clinical Pharmacology and Toxicology, University Hospital, Lausanne, Switzerland. eric.grouzmann@chuv.ch
Drouard-Troalen
Laurence
L
Baudin
Eric
E
Plouin
Pierre-François
PF
Muller
Beat
B
Grand
Daniela
D
Buclin
Thierry
T
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood* / Q000652:urine*; D008875:Middle Aged; D009647:Normetanephrine / Q000097:blood / Q000652:urine; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000652:urine; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D009647:Normetanephrine; D008676:Metanephrine