Biochemical diagnosis of pheochromocytoma: which test is best?
BACKGROUND
Diagnosis of pheochromocytoma depends on biochemical evidence of catecholamine production by the tumor. However, the best test to establish the diagnosis has not been determined.


OBJECTIVE
To determine the biochemical test or combination of tests that provides the best method for diagnosis of pheochromocytoma.


METHODS
Multicenter cohort study of patients tested for pheochromocytoma at 4 referral centers between 1994 and 2001. The analysis included 214 patients in whom the diagnosis of pheochromocytoma was confirmed and 644 patients who were determined to not have the tumor.


METHODS
Test sensitivity and specificity, receiver operating characteristic curves, and positive and negative predictive values at different pretest prevalences using plasma free metanephrines, plasma catecholamines, urinary catecholamines, urinary total and fractionated metanephrines, and urinary vanillylmandelic acid.


RESULTS
Sensitivities of plasma free metanephrines (99% [95% confidence interval [CI], 96%-100%]) and urinary fractionated metanephrines (97% [95% CI, 92%-99%]) were higher than those for plasma catecholamines (84% [95% CI, 78%-89%]), urinary catecholamines (86% [95% CI, 80%-91%]), urinary total metanephrines (77% [95% CI, 68%-85%]), and urinary vanillylmandelic acid (64% [95% CI, 55%-71%]). Specificity was highest for urinary vanillylmandelic acid (95% [95% CI, 93%-97%]) and urinary total metanephrines (93% [95% CI, 89%-97%]); intermediate for plasma free metanephrines (89% [95% CI, 87%-92%]), urinary catecholamines (88% [95% CI, 85%-91%]), and plasma catecholamines (81% [95% CI, 78%-84%]); and lowest for urinary fractionated metanephrines (69% [95% CI, 64%-72%]). Sensitivity and specificity values at different upper reference limits were highest for plasma free metanephrines using receiver operating characteristic curves. Combining different tests did not improve the diagnostic yield beyond that of a single test of plasma free metanephrines.


CONCLUSIONS
Plasma free metanephrines provide the best test for excluding or confirming pheochromocytoma and should be the test of first choice for diagnosis of the tumor.
Lenders
Jacques W M
JW
Department of Internal Medicine, St Radboud University Medical Center, Geert Grooteplein Zuid 8, PO Box 9101, 6500 HB, Nijmegen, the Netherlands. j.lenders@aig.azn.nl
Pacak
Karel
K
Walther
McClellan M
MM
Linehan
W Marston
WM
Mannelli
Massimo
M
Friberg
Peter
P
Keiser
Harry R
HR
Goldstein
David S
DS
Eisenhofer
Graeme
G
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood*; D008875:Middle Aged; D010673:Pheochromocytoma / Q000175:diagnosis* / Q000378:metabolism; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity
D002395:Catecholamines; D008676:Metanephrine