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"Although rare, these tumors are clinically important because they must be excluded as a surgically curable cause of hypertension in many of the people who develop high blood pressure," says Graeme Eisenhofer, Ph.D., a researcher in the Clinical Neurocardiology Section of the NINDS, and lead author of the study. "If the tumors are not diagnosed and removed, they can have potentially catastrophic consequences for the patient."
The mainly benign tumors, called pheochromocytomas, are sometimes found in patients with Von Hippel-Lindau (VHL) disease, a familial cancer syndrome with neurologic complications in which affected individuals inherit a predisposition to develop tumors in a number of organs, including the adrenal glands that sit atop the kidneys.
"Pheochromocytoma can occur in VHL patients as young as 8 years of age. Deaths from unsuspected adrenal gland tumors have been reported in young children in these families and it is important to make the diagnosis early so that surgical intervention can be performed," said W. Marston Linehan, M.D., NCI's Chief of Urologic Surgery.
A patient who develops pheochromocytomas for any reason is at risk for dangerous and unpredictable surges in blood levels of certain adrenal gland hormones that regulate blood pressure and which are responsible for the so-called "fight or flight" responses to stress. The surges in hormones and resulting spikes in blood pressure put the patient at risk for heart attack, stroke, hemorrhage, or sudden death.
Currently, the most reliable tests for pheochromocytomas use imaging technologies, such as MRI (magnetic resonance imaging), which can be time-consuming and expensive and which do not necessarily identify a tumor as a pheochromocytoma. Confirmatory biochemical tests are required for accurate diagnosis. Several biochemical tests are available which measure blood and urine levels of the adrenal gland hormones. But in many cases these tests are not accurate, because some pheochromocytomas do not release the adrenal hormones regularly or in significant amounts.
Drs. Eisenhofer, Linehan, and their colleagues found that these tumors contain an enzyme that continually transforms the adrenal hormones epinephrine and norepinephrine into the chemicals metanephrine and normetanephrine. Only pheochromocytomas produce these chemicals consistently in any significant quantity. Dr. Eisenhofer and colleagues hypothesized that measurements of blood levels of these two chemicals would give a more accurate diagnosis of pheochromocytomas.
Altogether, they measured the amounts of normetanephrine and metanephrine in 26 patients with VHL disease and 9 patients with multiple endocrine neoplasia type 2 (MEN2), another rare genetic disease characterized by pheochromocytomas. Use of the new test detected 97 percent of the tumors, whereas the other tests detected only 47 to 74 percent of tumors. Although particularly useful in diagnosis of tumors in VHL disease and MEN2, the test also shows promise for improved diagnosis of pheochromocytomas in the much larger population of patients with high blood pressure where the tumor needs to be excluded.
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1Eisenhofer, G.; Lenders, J.W.M.; Linehan, W.M.; Walther, M.M.; Goldstein, D.S.; Keiser, H.R. "Plasma normetanephrine and metanephrine for detecting pheochromocytoma in Von Hippel-Lindau disease and multiple endocrine neoplasia type 2." The New England Journal of Medicine, Vol. 340, No. 24, June 17, 1999, pp. 1872-1879.