Findings from five independent studies - with close to 350 patients with
pheochromocytoma and more than 2,500 in whom the
tumor was excluded - indicate that measurements of plasma free metanephrines provide an overall diagnostic sensitivity of 98% and specificity of 92%. The recommendation that initial testing for the
tumor should always include measurements of either plasma or urinary fractionated metanephrines results from recognition of the high diagnostic sensitivity of measurements of plasma metanephrines. The few patients with
pheochromocytoma in whom the test may not yield a positive result include those with very small
tumors or microscopic disease and others with
tumors that do not produce
norepinephrine and
epinephrine. Such patients are typically normotensive and do not exhibit symptoms of
catecholamine excess. Additional measurements of
methoxytyramine can be useful for detecting those
tumors that produce only
dopamine. Suboptimal diagnostic specificity and difficulties in distinguishing true- from false-positive elevations of plasma metanephrines remain challenges for diagnosis. Improvements in analytical technology (e.g., liquid chromatography with tandem mass spectrometry) and new strategies for follow-up testing provide possible solutions to these problems. The single most important remaining clinical care challenge is the development of effective cures for patients with malignant disease. Current treatments, none of which are truly satisfactory, include
chemotherapy and
radiopharmaceutical therapy with (131)I-labelled
M-iodobenzylguanidine or radioactive
somatostatin analogues. Improvements in treatment may in the future come from several fronts, but proof of efficacy ideally will require well-coordinated multicenter prospective trials in larger numbers of patients than in previous studies.