Advances in metanephrine testing for the diagnosis of pheochromocytoma Ravinder J. Singh, PhD Department of Laboratory Medicine & Pathology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA Pheochromocytoma is a lethal tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with the symptoms of palpitations, severe headaches, and sweating [1]. Although these symptoms are associated with the disease, at times pheochromocytoma can present with symptoms that mimic other clinical conditions. Pheochromocytomas are rare causes of hypertension, but they are dangerous tumors and thus require investigation in large numbers of patients. Pheochromocytomas have been estimated to be present in approximately 0.3% of patients undergoing eval- uation for secondary causes of hypertension. The diagnosis of pheo- chromocytoma is a challenging one; autopsy series suggest that many pheochromocytomas are not clinically suspected, and the undiagnosed tumor can be associated with morbid consequences [2]. Numerous cases have been reported, illustrating the fact that the diagnosis can be easily missed. The management of pheochromocytoma is now more promising than ever because of advancements in localization techniques and the availability of various effective treatment modalities [3]. Clinically patients with pheochro- mocytoma now can be operated on safely, but prolonged follow-up is essential, especially in those with hereditary forms of pheochromocytoma [4]. Over the last 30 years, various review articles have been published on the clinical features of pheochromocytoma [5–19]. This article focuses on the recent advances in the biochemical testing of metanephrines for the diagnosis of pheochromocytoma. Various tests for biochemical evidence of the disease are available, including; (1) urinary vanillylmandelic acid (VMA), (2) plasma catecholamines (PCATs), (3) urinary catecholamines (UCAT), (4) urinary total metanephrines, (5) urinary fractionated metanephrines (UMET), and (6) plasma-free metanephrines (PMET). In general, all of these tests are used for screening for pheochromocytoma, which can be an expensive ordeal for E-mail address: singh.ravinder@mayo.edu 0272-2712/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.cll.2004.01.015 Clin Lab Med 24 (2004) 85–103