Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas

J Clin Endocrinol Metab. 2009 May;94(5):1541-7. doi: 10.1210/jc.2008-2419. Epub 2009 Feb 17.


Purpose: The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.

Design: We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were performed to detect genomic rearrangements.

Results: Germline mutations were detected in 32.1% of cases, but frequencies varied widely depending on the classification criteria and ranged from 100% in patients with associated syndromic lesions to 11.6% in patients with a single tumor and a negative family history. The types and number of pheochromocytomas/paragangliomas as well as age at presentation and malignancy suggest which gene should be screened first. Genomic rearrangements were found in two of 160 patients (1.2%).

Conclusions: The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation. A positive family history and an accurate clinical evaluation of patients are strong indicators of which genes should be screened first.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / epidemiology
  • Adrenal Gland Neoplasms / genetics*
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Child
  • Cohort Studies
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Amplification
  • Gene Frequency
  • Genetic Testing
  • Germ-Line Mutation
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Paraganglioma / epidemiology
  • Paraganglioma / genetics*
  • Pheochromocytoma / epidemiology
  • Pheochromocytoma / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult


  • DNA