Should genetic testing be performed in each patient with sporadic pheochromocytoma at presentation?

Laboratoire de Biochimie Hormonologie, Métabolisme-Nutrition, Oncologie, Centre de Biologie et Pathologie, CHRU de Lille, France.
European Journal of Endocrinology (Impact Factor: 3.69). 12/2008; 160(2):227-31. DOI: 10.1530/EJE-08-0574
Source: PubMed

ABSTRACT 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.
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.
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.
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.
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.

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    ABSTRACT: Background The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.Objective To describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations.Methods We searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease.ResultsWe included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members.Conclusions The frequency of germline mutations in SPPs is approximately 11-13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.
    Clinical Endocrinology 06/2014; 82(3). DOI:10.1111/cen.12530 · 3.35 Impact Factor
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    ABSTRACT: Context:A number of incidentally discovered pheochromocytomas are not associated with hypertension. The characteristics of normotensive incidentally discovered pheochromocytomas (NIP) are poorly known.Objective:To assess the clinical, hormonal, histological and molecular features of NIPDesign:Retrospective cohort recruited from 2001 to 2011 in 2 tertiary-care medical departments.Patients and Methods:Clinical, biological and radiological investigations performed in 96 consecutive patients with sporadic unilateral pheochromocytomas were examined. 47 patients had overt pheochromocytomas responsible for hypertension. Among incidental pheochromocytomas, 28 patients had hypertension and 21 were normotensive (NIP). 62 tumors were examined for the PASS score, and 29 studied for the expression of 16 genes involved in chromaffin cell function.Results:Tumor size and MIBG scintigraphy results were similar between hypertensive pheochromocytomas (HP) and NIP. NIP patients displayed reduced summed levels of urinary catecholamines and metanephrines and, more specifically, reduced levels of adrenaline and metadrenaline compared to HP patients (P < 0.001). Urinary metanephrines had 98% diagnostic sensitivity in HP patients and only 75% in NIP patients (P < 0.01). Tumor diameter positively correlated with total amount of urinary concentrations of metanephrines in HP patients, (P < 0.001) but not in NIP patients. NIP displayed a global decreased chromaffin genes expression, reaching significance for 5 of them and 2 corresponding proteins: Phenylethanolamine N-methyltransferase, secretogranin II, and a significant increase in the cellularity, mitotic activity, and presence of atypical mitosis (P < 0.05).Conclusions:Normotensive incidentally discovered pheochromocytomas differ from pheochromocytomas responsible for hypertension and display features of altered chromaffin differentiation. Usual biological diagnostic tools may misdiagnose these tumors.
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    ABSTRACT: Pheochromocytomas are catecholamine producing neuroendocrine tumors that can be adrenal or extra-adrenal in origin. The classic symptoms of pheochromocytoma are headache, palpitation, anxiety and diaphoresis and the tumor can occur at any age with equal gender distribution. In patients with an established mutation or hereditary syndrome the condition may manifest at a younger age than in those with sporadic disease. Pheochromocytoma can be associated with certain genetic syndromes such as multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis (NF) and von Hippel-Lindau (VHL) syndrome. Pheochromocytoma is diagnosed with biochemical confirmation of hormonal excess followed by anatomical localization (CT or MRI). The mainstay of definitive therapy is surgical resection. In this review, we discuss in detail about the symptomatology, diagnosis, genetic aspects and management of pheochromocytoma.
    Maturitas 01/2014; DOI:10.1016/j.maturitas.2013.12.009 · 2.86 Impact Factor


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