Plasma normetanephrine and metanephrine for detecting pheochromocytoma in Von Hippel-Lindau disease and multiple endocrine neoplasia type 2

Background. The detection of pheochromocytomas in patients at risk for thes e tumors, such as patients with von Hippel-Lindau disease or multiple endoc rine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measureme nts of plasma normetanephrine and metanephrine for detecting pheochromocyto mas in patients with von Hippel-Lindau disease or MEN-2. Methods. We studied 26 patients with von Hippel-Lindau disease and 9 patien ts with MEN-2 who had histologically verified pheochromocytomas and 50 pati ents 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 conc entrations of normetanephrine and metanephrine were compared with the plasm a concentrations of catecholamines (norepinephrine and epinephrine) and uri nary excretion of catecholamines, metanephrines, and vanillylmandelic acid. Results. The sensitivity of measurements of plasma normetanephrine and meta nephrine for the detection of tumors was 97 percent, whereas the other bioc hemical 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 concentr ations 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 plasm a normetanephrine and metanephrine was accompanied by a high level of speci ficity (96 percent). Conclusions. Measurements of plasma normetanephrine and metanephrine are us eful in screening for pheochromocytomas in patients with a familiar predisp osition to these tumors. (N Engl J Med 1999; 340:1872-9.) (C) 1999, Massach usetts Medical Society.