SAT310 Single Institution Retrospective Case Cohort Of Adult Cyanotic Congenital Heart Disease And Associated Pheochromocytoma And Paraganglioma
Authors: Jones Robert Benson , Bennett Bonita , Cohen Debbie 
Published: October 2023

Disclosure: R.B. Jones: None. B. Bennett: None. D. Cohen: Consulting Fee; Self; Novartis Pharmaceuticals, Consultant, Medtronic, Consultant, Recor, Consultant. Grant Recipient; Self; Medtronic, Research Support, Recor, Research Support. Other; Self; Metavention, DSMB.

Introduction: Improved management for patients with cyanotic congenital heart disease (CCHD) has led to prolonged lifespan and a noticeable increase in patients with CCHD presenting with pheochromocytoma and paraganglioma (PPGL). PPGL susceptibility genes including VHL, SDH(x), FH, EPAS1 have been connected to a common signaling pathway that activates hypoxia-inducible factors (HIF). 4 of 5 patients with CCHD and PPGL were reported to have a somatic gain-of-function mutation in EPAS1 encoding HIF-2α. One hypothesis is that the hypoxic environment positively selects for cells with gain-of-function mutations predisposing patients to develop PPGL even when environment is no longer hypoxic. PPGL was diagnosed 13-53 years after surgical correction of CCHD in these patients. We report a case series on 9 CCHD/PPGL patients treated at our institution. Objective: To describe a cohort of patients with CCHD who developed PPGLs. Methods: A retrospective chart review of patients with CCHD treated for PPGL at our institution was performed describing demographics, CCHD and related treatments, symptoms of PPGL and Hct/SpO2 at diagnosis, tumor size, catecholamine biochemistries, imaging and genetic analysis when available. Results: Four of 9 patients were female. Average age of diagnosis of PPGL was 30.7 years (SD 9.6 years, range 15-47 years). CCHD anomalies included Tetralogy of Fallot (2), hypoplastic right ventricle (2) and hypoplastic left ventricle (2). Most surgeries to correct CCHD were performed within days of life; the latest reported surgical procedure was at age 12, 1 patient had a subsequent heart transplant. Patients experienced hot flashes (5), arrhythmias (4), hypertension (4), abdominal pain and nausea (2), headaches (1) and asymptomatic (1). Hct and SpO2 ranged from 38%-53% and 85%-99% respectively. Three patients had multiple PPGLs; 2 had metastatic or recurrent PPGL. Metanephrines at diagnosis ranged from normal to 23x the upper limit of normal (ULN). Catecholamines ranged from normal to 16x ULN. Location of PPGL included 6 mediastinal and abdominal paraganglioma (PGLs), 5 head and neck PGLs, and 3 pheochromocytomas. Tumor size ranged from 9-65mm at maximum diameter on pathology. 7/9 patients had germline mutation testing; one SDHB mutation, one SDHA mutation of undetermined significance, and one BARD1 mutation were identified. Conclusions: The extended timeframe between onset of cyanosis and development of PPGL supports long term regular monitoring of CCHD patients to detect PPGL. We suggest screening with plasma metaneprines and catecholamines at age 15 and every 3-5 years after. References: Vaidya A, Flores SK, Cheng Z-M, Nicolas M, Deng Y, et al. (2018) EPAS1 Mutations and Paragangliomas in Cyanotic Congenital Heart Disease. N Engl J Med 378: 1259-1261.

Presentation: Saturday, June 17, 2023