Clinical Chemistry
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Clinical Chemistry 53: 1565-1567, 2007; 10.1373/clinchem.2007.089128
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(Clinical Chemistry. 2007;53:1565-1567.)
© 2007 American Association for Clinical Chemistry, Inc.

Editorials

High-Throughput, Automated, and Accurate Biochemical Screening for Pheochromocytoma: Are We There Yet?

Ravinder J. Singh1,a and Graeme Eisenhofer2

1 Department of Laboratory Medicine, and Pathology, Mayo Clinic, Rochester, MN
2 Departments of Clinical Chemistry, and Medicine, University of Dresden, Dresden, Germany

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.

Biochemical testing for pheochromocytoma is a diagnostic challenge due both to the highly variable nature of this rare catecholamine-producing tumor and the technical demands required for accurate and reliable laboratory tests of catecholamine excess. In this issue of Clinical Chemistry, de Jong et al. (1) describe a high-throughput automated liquid–chromatography-tandem mass spectrometry (LC-MS/MS) method enabling simultaneous extraction, concentration, separation, and mass-selective detection of plasma free normetanephrine and metanephrine, the respective O-methylated metabolites of norepinephrine, and epinephrine. This method for measurements of plasma free metanephrines (Note: the term "metanephrines" refers to both normetanephrine and metanephrine) also allows quantification of methoxytyramine, the O-methylated derivative of dopamine and a metabolite normally present in plasma at lower concentrations (<0.1 nmol/L) than free normetanephrine (<0.6 nmol/L) or metanephrine (<0.3 nmol/L).

Recognition that catecholamines are metabolized to free metanephrines within pheochromocytoma tumor cells, and that this process is independent of catecholamine release, provides a rationale for use of these metabolites in the diagnosis of pheochromocytoma (2). The diagnostic superiority of metanephrines over catecholamines has led to the recommendation that initial testing for pheochromocytoma should always include measurements of metanephrines in plasma or urine or both (3). Metanephrines in urine are usually measured after an acid hydrolysis step that converts the high concentrations of sulfate-conjugated metabolites into free metanephrines. In part because of this step, concentrations of metanephrines in urine are 2–3 orders of magnitude higher than those for the free metanephrines in plasma. These higher concentrations, along with the simpler matrix, make urinary metanephrines easier to measure than plasma free metanephrines. However, the enzyme responsible for sulfate conjugation is present mainly in gastrointestinal tissues (2). Thus, the free metanephrines produced within tumor cells . . . [Full Text of this Article]






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