Catecholamine-Secreting Tumors in Pediatric Patients With Cyanotic Congenital Heart Disease

Abstract

Catecholamine-secreting tumors are rare among the pediatric population but are increasingly being reported in children with sustained hypoxia secondary to cyanotic congenital heart disease (CCHD). With this review, we report the clinical characteristics of these tumors in children with CCHD. The articles included in the present review were identified using PubMed through February 2019. A manual search of the references retrieved from relevant articles was also performed. Pheochromocytomas and paragangliomas (PPGL) in children are commonly associated with high-risk germline or somatic mutations. There is evidently a higher risk of tumorigenesis in children with CCHD as compared with the general pediatric population, even in the absence of susceptible gene mutations. This is due to molecular mechanisms involving the aberrant activation of hypoxia-response elements, likely secondary to sustained hypoxemia, resulting in tumorigenesis. Due to overlapping symptoms with CCHD, the diagnosis of PPGL may be delayed or missed in these patients. We studied all previously reported PPGL cases in children with CCHD and reviewed phenotypic and biochemical features to assess for contributing factors in tumorigenesis. Larger studies are needed to help determine other potential predisposing factors and to establish screening guidelines in this high-risk population. A delay in diagnosis of the PPGL tumors can lead to exacerbation of cardiac failure, and therefore early diagnosis and intervention may provide better outcomes in these patients, necessitating the need for regular surveillance. We recommend routine biochemical screening in patients with sustained hypoxia secondary to CCHD.

JCS 2022 Guideline on Management and Re-Interventional Therapy in Patients With Congenital Heart Disease Long-Term After Initial Repair

“…In patients with cyanotic malformations, it may be worth screening for renal impairment, pheochromocytoma, and paraganglioma. 400 Urinalysis, blood glucose levels, hematocrit, lipid panel, basic metabolic panel, and calcium levels are informative. Sarcopenia is not rare in ACHD.…”

Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency

“…Recently, mutations in SDHA ( 21 ) and SDHAF2 were also identified in hereditary PHEOs and PGLs ( 40 ). In addition, multiple reports have shown that these tumors have high incidence in patients with cyanotic congenital heart disease ( 41 – 43 ).…”

The HARMONIC project: Study design for assessment of cancer risks following cardiac fluoroscopy in childhood

“…Patients with congenital heart disease (CHD) are known to be at increased risk of cancer [23][24][25]51]. Explanations include shared genetic and environmental risk factors, altered blood flow and hypoxia resulting from the disease itself or surgery such as Fontan's procedure [52,53], as well as radiation exposure. If the underlying disease is associated with both increased risk of cancer and increased radiation exposure, the dose/risk relationship may be confounded (Figure 2).…”