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Congenital Cyanotic Heart Disease and the Association with Pheochromocytomas and Paragangliomas

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Abstract

Purpose of Review

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that commonly produce excess catecholamines causing significant morbidity and mortality. Patients with cyanotic congenital heart disease (CCHD) develop PPGLs at a higher frequency than the general population. This review will summarize recent research in the association of PPGL and CCHD.

Recent Findings

Advances in molecular genetics have provided new insights into a variety of germline mutations and somatic mutations related to PPGLs. In the CCHD population, mutations can occur in the hypoxia signaling pathway with gain-of-function somatic mutations in EPAS1, which prevent degradation of hypoxia-inducible factor-2 alpha. These mutations are implicated in oncogenesis. PPGLs associated with CCHD develop as early as age 15 years and have predominantly noradrenergic secretion. Surgical removal is considered the first line of therapy, although belzutifan, a HIF-2α inhibitor, is currently being tested as a potential therapy.

Summary

Early screening with plasma metanephrines may assist in identifying PPGLs in patients with CCHD.

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Data Availability

The data that support the findings of this study are not openly available and are available from the corresponding author upon reasonable request.

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  1. Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Robert Benson Jones Jr.

  2. Division of Renal Electrolyte and Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Debbie L. Cohen

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Jones, R.B., Cohen, D.L. Congenital Cyanotic Heart Disease and the Association with Pheochromocytomas and Paragangliomas. Curr Cardiol Rep 25, 1451–1460 (2023). https://doi.org/10.1007/s11886-023-01974-8

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