Pediatric Metastatic Pheochromocytoma and Paraganglioma: Clinical Presentation and Diagnosis, Genetics, and Therapeutic Approaches

作者：Mickey J. M. Kuo, Matthew A. Nazari, Abhishek Jha, Karel Pacák · 发表于：Frontiers in Endocrinology · 年份：2022 · DOI：10.3389/fendo.2022.936178 · 被引用次数：24 · 研究领域：Adrenal and Paraganglionic Tumors、Cancer, Hypoxia, and Metabolism、Pituitary Gland Disorders and Treatments

Although pediatric pheochromocytomas and paragangliomas (PPGLs) are rare, they have important differences compared to those in adults. Unfortunately, without timely diagnosis and management, these tumors have a potentially devastating impact on pediatric patients. Pediatric PPGLs are more often extra-adrenal, multifocal/metastatic, and recurrent, likely due to these tumors being more commonly due to a genetic predisposition than in adults. This genetic risk results in disease manifestations at an earlier age giving these tumors time to advance before detection. In spite of these problematic features, advances in the molecular and biochemical characterization of PPGLs have heralded an age of increasingly personalized medicine. An understanding of the genetic basis for an individual patient’s tumor provides insight into its natural history and can guide clinicians in management of this challenging disease. In pediatric PPGLs, mutations in genes related to pseudohypoxia are most commonly seen, including the von Hippel-Lindau gene ( VHL ) and succinate dehydrogenase subunit ( SDHx ) genes, with the highest risk for metastatic disease associated with variants in SDHB and SDHA . Such pathogenic variants are associated with a noradrenergic biochemical phenotype with resultant sustained catecholamine release and therefore persistent symptoms. This is in contrast to paroxysmal symptoms (e.g., episodic hypertension, palpitations, and diaphoresis/flushing) as seen in the adrenergic, or ...