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Precisely Wrong? Urinary Fractionated Metanephrines and Peer-Based Laboratory Proficiency Testing

Departments of,¹ Laboratory Medicine and Pathology, and ² Medicine, Mayo Clinic, Rochester, MN
³ ARUP Institute for, Clinical and Experimental Pathology, Salt Lake City, UT
⁴ Laboratory of Bioorganic Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, NIH, Bethesda, MD
⁵ Department of Pathology, and Laboratory Medicine, Berkshire Health System, Pittsfield, MA
⁶ Clinical Neurocardiology Section, National Institute of, Neurological Disorders and Stroke, NIH, Bethesda, MD

^aAddress correspondence to this author at: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905. Fax 507-284-9758; e-mail Singh.Ravinder@mayo.edu.

The first 20% of the full text of this article appears below.

To the Editor:

Measurements of urinary fractionated metanephrines (normetanephrine and metanephrine), the O-methylated metabolites of norepinephrine and epinephrine, provide a sensitive test for diagnosis of pheochromocytoma. We present evidence suggesting inaccurate metanephrine and normetanephrine calibration by US laboratories.

Metanephrines are present in urine mainly as sulfate- and glucuronide-conjugated metabolites produced from free metanephrines by the actions of conjugating enzymes (1). An acid hydrolysis step is usually performed to liberate the free metanephrines from the conjugated metabolites. This step minimizes requirements for high analytical sensitivity, simplifying subsequent measurement.

Urinary fractionated metanephrines are usually measured by HPLC with electrochemical detection (HPLC-EC). Gas chromatography with mass spectrometry (GC-MS) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) are more recent alternatives offering high sample throughput and improved analytical specificity (2)(3).

Clinical laboratories in the US participate in proficiency testing programs, primarily aimed at determining agreement in diagnostic test results among laboratories. Identical survey samples are distributed to participating laboratories, with results stratified according to testing methodologies. Laboratories that report results deviating by more than a certain amount from the mean of their peer groups fail the proficiency test.

Until the spring of 2004, the only source of commercially available urine metanephrine calibrators in the US was Bio-Rad. . . . [Full Text of this Article]

Steven Binder

^R1 Bio-Rad Laboratories, Clinical HPLC Group, 4000 Alfred Nobel Dr., Hercules, CA 94547

^aE-mail steve_binder@bio-rad.com

The following articles in journals at HighWire Press have cited this article:

				E. Grouzmann, B. Mathian, and T. Buclin Calibration of Fractionated Metanephrines in Urine: Still an Issue? Clin. Chem., October 1, 2008; 54(10): 1738 - 1739. [Full Text] [PDF]

				R. J. Singh and G. Eisenhofer High-Throughput, Automated, and Accurate Biochemical Screening for Pheochromocytoma: Are We There Yet? Clin. Chem., September 1, 2007; 53(9): 1565 - 1567. [Full Text] [PDF]