Ces Urol 2010, 14(1):5-15 | DOI: 10.48095/cccu2010002

Pheochromocytoma and paraganglioma syndromes: going on 2010

Karel Pacak¹, Tamara Prodanov¹, Graeme Eisenhofer³, Karen Adams¹, Vitaly Kantorovich²

¹ Reproductive Biology and Medicine Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), MD, USA

² Division of Endocrinology and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

³ Departments of Medicine and Clinical Chemistry, University of Dresden, Dresden, Germany

Pheochromocytomas and paragangliomas are chromaffin cell tumors that produce, store (e.g. in vesicles), metabolize (e.g. to yield metabolites such as normetanephrine or metanephrine), and secrete (release) catecholamines (e.g. norepinephrine and epinephrine, or dopamine). The metabolism of catecholamines is a more consistent process than that of catecholamine secretion. Pheochromocytomas are found in the adrenal gland; closely related tumors of extra-adrenal location are classified as paragangliomas. Most pheochromocytoma and paraganglioma tumors (PTTs) represent sporadic tumors but about 20-30% of these tumors are familial. Mutations in six genes to date have been identified to be responsible for familial PTTs: 1. the von Hippel-Lindau (VHL) gene leading to VHL syndrome; 2. the RET gene leading to multiple endocrine neoplasia type 2; 3. the neurofibromatosis type 1 (NF-1) gene associated with von Recklinghausens disease; and 4 and 5. mutations of genes encoding the B, C, and D subunits of mitochondrial succinate-dehydrogenase (SDHB, SDHC, and SDHD) associated with familial PTTs. The presence of catecholamine excess reflects various clinical signs and symptoms associated with PTTs. Hypertension is the most common sign and may be sustained or paroxysmal. Numerous independent studies have now confirmed that measurements of fractionated metanephrines (i.e. normetanephrine and metanephrine measured separately) in urine or plasma provide superior diagnostic sensitivity over measurement of the parent catecholamines. Current localization of PTTs should be based on the use of anatomical as well as specific functional imaging studies to proof that a tumor is indeed pheochromocytoma or paraganglioma. Laparoscopic surgery is now the technique of first choice for resection adrenal and extra-adrenal PTTs. All patients with PTTs should receive appropriate preoperative medical management to block the effects of released catecholamines (blocking the synthesis and the action of catecholamines). Currently, there is no curative treatment for malignant PTTs.

Keywords: pheochromocytoma, paraganglioma, catecholamines, metanephrines, neuroendocrine, familial, metaiodobenzylguanidine scintigraphy, postitron emission tomography

Published: January 1, 2010