Fractionated metanephrines

After the potential confounding influence of medications or other causes of false-positive results have been eliminated, some consideration should be given to the choice of additional biochemical tests and patterns of results necessary for more firmly establishing or refuting the diagnosis of a pheochromocytoma. When initial testing yields elevations in plasma normetanephrine, metanephrine, or both amines, this may be corroborated by a similar pattern of results after additional measurements of urinary normetanephrine and metanephrine. Conversely, when initial testing yields positive results for urinary fractionated metanephrines, additional measurements of plasma free metanephrines are useful. 

Interpretation of a biochemical test result as normal or abnormal depends on availability of valid reference intervals (see Chapter 16). For tests of a single analyte, such as VMA, it can be expected that at least 2.5% of patients without pheochromocytomas will have values for the analyte above the upper reference limit and 2.5% below the lower reference limit. Up to a 5% incidence of false-positive results might be expected for tests of pairs of analytes, such as norepinephrine and epinephrine in tests of urinary or plasma catecholamines or normetanephrine and metanephrine in tests of plasma free or urinary fractionated metanephrines. False-positive rates usually, however, tend to be higher than expected this is likely due to reduced control over sampling conditions and sources of interference or differences in clinical characteristics of reference and patient populations. 

The high diagnostic sensitivity of measurements of plasma free or urinary fractionated normetanephrine and metanephrine makes these tests the most suitable choice for the initial work up of a patient with a suspected pheochromocytoma. Negative results by these tests virtually exclude a pheochromocytoma, whereas negative results by other tests do not. Exceptions include small or microscopic ([Pg.1047]

In contrast to the catecholamines, measurements of urinary metanephrines and VMA are still based in some routine laboratories on the early spectrophotometric assays developed by Pisano, Crout, and others in the late 1950s and early 1960s. Despite subsequent development of a variety of preanalytical cleanup and extraction procedures, these assays remain susceptible to analytical interference. They are also restricted to measurements in urine. Another limitation for spectrophotometric or fiuorometric assays of urinary metanephrines is that these methods do not allow separate (fractionated) measurements of normetanephrine and metanephrine. 

Sawka AM, Jaeschke R, Singh RJ, Young WF, Jr. A comparison of biochemical tests for pheochromocytoma measurement of fractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines,... 

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