CLINICAL STUDY Should genetic testing be performed in each patient with sporadic pheochromocytoma at presentation? Pascal Pigny, Catherine Cardot-Bauters 1 , Christine Do Cao 1 , Marie Christine Vantyghem 1 , Bruno Carnaille 2 , Franc ¸ois Pattou 2 , Philippe Caron 3 , Jean-Louis Wemeau 1 and Nicole Porchet Laboratoire de Biochimie ‘Hormonologie, Me ´tabolisme-Nutrition, Oncologie’, Centre de Biologie et Pathologie, CHRU de Lille, France, 1 Service d’Endocrinologie et Me ´tabolismes, Clinique Marc Linquette, CHRU de Lille, 59037 France, 2 Service de Chirurgie Endocrinienne, Ho ˆpital Claude Huriez, CHRU de Lille, France and 3 Service d’Endocrinologie et Maladies Me ´taboliques, Ho ˆpital Larrey, CHU de Toulouse, 31059 France (Correspondence should be addressed to P Pigny; Email: p-pigny@chru-lille.fr) Abstract Background: According to previous studies, around 15% of patients with an apparently sporadic pheochromocytoma and a negative family history had a hereditary disease. This high frequency together with the financial support provided to reference laboratories of molecular genetics by the French government led to a nearly systematic screening in each patient with a pheochromocytoma. Objective: To check the efficiency of systematic genetic screening in patients with apparently sporadic pheochromocytoma, by analysing the 6 years experience of a multidisciplinary team in this field. Methods: One hundred patients with a pheochromocytoma-only phenotype and no family history were included. Patients with extra-adrenal tumours were excluded. Prevalence of hereditary forms was determined and analyzed according to age at onset, sex. Cost of the genetic analysis was calculated. Results: A germline mutation in one of the five susceptibility genes (VHL, RET , SDHD, SDHC, SDHB) was identified in eight patients (8%) with an age of onset between 13 and 57 years. Among them, six had a bilateral pheochromocytoma and only two had a unilateral tumour. If the guidelines for genetic screening were age of onset less than 50 or bilateral pheochromocytoma, no patients with a hereditary tumour would be missed and a 24% cost reduction would be achieved. Conclusions: According to these data, a genetic predisposition test for hereditary pheochromocytoma seems not recommended in patients with a unilateral adrenal tumour diagnosed after 50 in the absence of familial, clinical, biological or imaging features for a familial disease. European Journal of Endocrinology 160 227–231 Introduction Pheochromocytomas are rare catecholamine-produ- cing tumours that arise from chromaffin cells of the adrenal medulla. They are closely linked to paragan- gliomas that develop from others extra-adrenal neural crest derived cells such as parasympathetic or sym- pathetic paraganglia (1). However, pheochromocyto- mas are more commonly recognized because clinicians often focus on adrenal glands as the main source of catecholamine hypersecretion. Until 1999, only 10% of all pheochromocytomas were considered as hereditary tumours, and were part of multiple tumour syndromes such as multiple endocrine neoplasia type 2 (due to a germline mutation of the RET proto-oncogene), von Hippel–Lindau disease (VHL tumour-suppressor gene) or neurofibromatosis type 1 (NF1 tumour-suppressor gene) that are inherited on an autosomal-dominant mode. In the early 2000s, new susceptibility genes for hereditary pheochromocytomas and/or paragangliomas were discovered. These genes named SDHD, SDHB and SDHC encode three of the four protein subunits of the succinate dehydrogenase (SDH) also known as mitochondrial complex II (2). Therefore, at least six susceptibility genes for familial pheochromocy- tomas are now known (a number that could still expand in the next future (3)). The rapid transfer of these research data from the bench to the bedside has allowed re-evaluation of the true prevalence of hereditary forms of these adrenal tumours. Thus, in 2002, Prof Neumann from Freiburg University first demonstrated, by perform- ing genetic testing in a cohort of 271 patients who presented apparently sporadic pheochromocytoma (in fact 241 with isolated pheochromocytoma), that about 24% of the patients did harbour a germline mutation of RET , SDHD, VHL or SDHB thus revealing a hereditary syndrome (4). However, exclusion of patients with a positive family history would decrease the rate of hereditary forms to 15.5% (4). In 2003, we reported a similar prevalence (15%) by studying simultaneously five susceptibility genes (the former and SDHC) in 13 index cases (5). At the same time in France, President J. Chirac implanted the ‘Plan Cancer’ whose aim number 22 was to improve the access to genetic testing by providing a European Journal of Endocrinology (2009) 160 227–231 ISSN 0804-4643 q 2009 European Society of Endocrinology DOI: 10.1530/EJE-08-0574 Online version via www.eje-online.org