Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Division of Renal Electrolyte and Hypertension, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Curr Cardiol Rep. 2023 Nov;25(11):1451-1460. doi: 10.1007/s11886-023-01974-8. Epub 2023 Oct 17.
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.
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. Early screening with plasma metanephrines may assist in identifying PPGLs in patients with CCHD.
嗜铬细胞瘤和副神经节瘤（PPGL）是罕见的神经内分泌肿瘤，通常会产生过量的儿茶酚胺，导致严重的发病率和死亡率。患有发绀型先天性心脏病（CCHD）的患者比一般人群更常发生 PPGL。本综述将总结 PPGL 和 CCHD 之间关联的最新研究。
分子遗传学的进展为与 PPGL 相关的各种种系突变和体细胞突变提供了新的见解。在 CCHD 人群中，突变可能发生在缺氧信号通路中，EPAS1 的功能获得性体细胞突变阻止缺氧诱导因子-2α的降解。这些突变与肿瘤发生有关。与 CCHD 相关的 PPGL 早在 15 岁就已发病，主要分泌去甲肾上腺素。手术切除被认为是一线治疗方法，尽管 HIF-2α 抑制剂贝伐单抗目前正在作为一种潜在的治疗方法进行测试。对 CCHD 患者进行血浆间甲肾上腺素的早期筛查可能有助于识别 PPGL。
