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Previous Volume 340:1872-1879 June 17, 1999 Number 24 Next

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ABSTRACT

Background The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel–Lindau disease or multiple endocrine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measurements of plasma normetanephrine and metanephrine for detecting pheochromocytomas in patients with von Hippel–Lindau disease or MEN-2.

Methods We studied 26 patients with von Hippel–Lindau disease and 9 patients with MEN-2 who had histologically verified pheochromocytomas and 50 patients with von Hippel–Lindau disease or MEN-2 who had no radiologic evidence of pheochromocytoma. Von Hippel–Lindau disease and MEN-2 were diagnosed on the basis of germ-line mutations of the appropriate genes. The plasma concentrations of normetanephrine and metanephrine were compared with the plasma concentrations of catecholamines (norepinephrine and epinephrine) and urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid.

Results The sensitivity of measurements of plasma normetanephrine and metanephrine for the detection of tumors was 97 percent, whereas the other biochemical tests had a sensitivity of only 47 to 74 percent. All patients with MEN-2 had high plasma concentrations of metanephrine, whereas the patients with von Hippel–Lindau disease had almost exclusively high plasma concentrations of only normetanephrine. One patient with von Hippel–Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (<1 cm). The high sensitivity of measurements of plasma normetanephrine and metanephrine was accompanied by a high level of specificity (96 percent).

Conclusions Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familial predisposition to these tumors.

Source Information

From the Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke (G.E., D.S.G.), the Urologic Oncology Branch, National Cancer Institute (W.M.L., M.M.W.), and the Hypertension Endocrine Branch, National Heart, Lung, and Blood Institute (H.R.K.) — all at the National Institutes of Health, Bethesda, Md.; and the Department of General Internal Medicine, St. Radboud University Hospital, Nijmegen, the Netherlands (J.W.M.L.).

Address reprint requests to Dr. Eisenhofer at Bldg. 10, Rm. 6N252, National Institutes of Health, 10 Center Dr., MSC-1620, Bethesda, MD 20892-1620, or at ge{at}box-g.nih.gov.

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