Imaging Work-Up for Screening of Paraganglioma and Pheochromocytoma in SDHx Mutation Carriers: A Multicenter Prospective Study from the PGL.EVA Investigators

Context: Recommendations have not been established concerning imaging to screen SDHx mutation carriers for paraganglioma and pheochromocytoma. Objective: Our objective was to compare the performance of gadolinium-enhanced magnetic resonance angiography, contrast-enhanced computed tomography, and [123I]metaiodo-benzylguanidine and somatostatin receptor scintigraphies for detecting head and neck and thoracic-abdominal-pelvic paragangliomas in SDHx mutation carriers. Design and Setting: We conducted a prospective, multicenter study from June 2005 to December 2009 at 23 French medical centers. Patients: A total of 238 index cases or relatives carrying mutations in SDHD, SDHB, or SDHC genes were included. Intervention: Images obtained by each technique were analyzed blind, without knowledge of results from other tests, first in each local center and then centrally. Main Outcome Measures: We evaluated sensitivity, specificity, and likelihood ratios for individual and combinations of tests, the gold standard being the consensus of an expert committee. Results: Two hundred two tumors were diagnosed in 96 subjects. At local assessment, the sensitivity of anatomical imaging for detecting all tumors was higher (85.7%) than that of both scintigraphic techniques (42.7% for [123I]metaiodo-benzylguanidine and 69.5% for somatostatin receptor scintigraphy), except for thoracic localizations where somatostatin receptor scintigraphy was more sensitive (61.5 vs. 46.2% for anatomical imaging and 30.8% for [123I]metaiodo-benzylguanidine scintigraphy). The best diagnostic performance during local assessment was obtained by combining anatomical imaging tests and somatostatin receptor scintigraphy (sensitivity 91.7%). Central assessment significantly increased the sensitivity (98.6%) of tests in combination. Conclusions: In routine practice, the imaging work-up for screening SDHx mutation carriers should include thoraco-abdomino-pelvic computed tomography, head and neck magnetic angiography, and somatostatin receptor scintigraphy. Expert centralized image assessment is recommended.