Cardiac Paragangliomas are Commonly Associated with Succinate Dehydrogenase Gene Mutations

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 130-162-Neuroendocrinology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-136
Jaydira Del Rivero*1, Abbas Emaminia2, Analyza del Mundo Galia3, Steve Leung4, Roberto Lorusso5, Camilo Jimenez6, Barry Lynn Shulkin7, Jennifer L Audibert4, Karen T Adams1, Douglas Rosing4, Antonio Fojo8, Anand Vaidya9, Eizabeth G Loughran9, Robert G Dluhy9, Keith Horvath2 and Karel Pacak10
1Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 2Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, Bethesda, MD, 3St. Elizabeth Hospital, Gen Santos City, Philippines, 4Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, 5Cardiac Surgery Unit, Brescia, Italy, 6The University of Texas MD Anderson Cancer Center, Houston, TX, 7Division of Nuclear Medicine, Memphis, TN, 8National Cancer Institute, Bethesda, MD, 9Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 10National Institutes of Health (NIH), Bethesda, MD
Introduction: Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. One-third of these tumors are familial  which are inherited through eleven known genes (RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, NF1, TMEM127, MAX, HIF2α). Cardiac paragangliomas are rare tumors and constitute less than 1% of all cardiac tumors. Recent improvements in molecular genetics have described genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD to cause paragangliomas in the thoracic cavity with aggressive tumor behavior. The purpose of this study was to determine the role of SDHx genes in patients with cardiac paragangliomas. We hypothesized that cardiac paragangliomas are associated with a high occurrence of SDHx genes.

Methods: A multi-institutional study enrolled twelve patients with cardiac paragangliomas. Genetic testing for SDHx was performed by multiplex PCR. All patients underwent functional imaging studies, transthoracic echocardiography, followed by cardiac CT or cardiac MRI to determine the exact site of involvement and vascularity of the tumor. All cases but one underwent surgical resection of the cardiac tumor and were followed for up to 34 years.

Results: 5/12 patients were males (41%) and average age was 41 years. Typical symptoms of paraganglioma (paroxysmal hypertension, palpitation, headache) were the initial presentation in 83% of cases (10 patients), while cardiac-specific symptoms (chest pain) were noticed in only 2 patients (17%). Genetic testing was done in 10 cases (83%), out of which 70% were positive for SDHB, C, or D mutations. Eleven cases (91%) required cardiac surgery to remove the paraganglioma tumor with no intraoperative morbidity and mortality after receiving adequate preoperative management with adrenergic blockade to prevent catecholamine crisis.

Discussion: SDHx mutation is known to be associated with mediastinal location and malignant behavior of paragangliomas.  These tumors are rare and may present with symptoms related to catecholamine excess. Furthermore, surgery remains the mainstay of therapy in these patients. This is the first report that identifies the role of SDH B, D, and C mutations in the location of such tumors in the heart. Genetic testing of all patients with cardiac tumors helps physicians make earlier diagnoses and guides proper surgical management.

Nothing to Disclose: JD, AE, ADMG, SL, RL, CJ, BLS, JLA, KTA, DR, AF, AV, EGL, RGD, KH, KP

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