Pheochromocytoma complicated by cyanotic congenital heart disease: a case report

In the pediatric population, the reported incidence of pheochromocytoma (PHEO) is as high as 0.3 per million per year (1). Most cases are sporadic, and according to Waguespack et al., 56% of patients with sporadic PHEO who are less than 18 yr of age have germline DNA mutations (1). Genes thought to be associated with PHEOs include the RET proto-oncogene, VHL (von Hippel-Lindau), NF1 (neurofibromin 1), SDHB (succinate dehydrogenase complex subunit B), SDHD (succinate dehydrogenase complex subunit D), SDHAF2 (succinate dehydrogenase complex assembly factor 2), TMEM127 (transmembrane protein 127), Max (Myc-associated factor X), PHD2 (prolyl hydroxylase 2), H-RAS (Harvey rat sarcoma viral oncogene), and HIF2A (hypoxia-inducible factor 2α) (2, 3). Hypoxia may be a risk factor for PHEO along with genetic abnormalities. Because the protein products of VHL and SDH mediate the cellular response to hypoxia by activating the hypoxia-inducible factor (HIF) signaling pathway, a pseudohypoxic mechanism may underlie PHEO (the pseudohypoxia hypothesis) (2, 4). The MAPK (mitogen-activated protein kinase) and mTOR (mammalian target of rapamycin) signaling pathways have also been implicated in the development of PHEO (2, 4). Although the direct relationship between systemic hypoxia and PHEO development is unclear, several cases of PHEO in patients with cyanotic congenital heart disease (CCHD) have been reported (5,6,7,8,9,10,11,12,13,14,15,16). According to a recent estimate, patients with CCHD have a greater risk of developing PHEO or paraganglioma (odds ratio: 6.0) than do those with non-cyanotic congenital heart disease (odds ratio: 0.9) (17). In addition, an epidemiologic study reported a relatively high incidence of PHEO in people living at high altitudes (18). These findings link CCHD and hypoxia with PHEO. Here, we present a case of PHEO and tricuspid atresia (TA) that was treated by performing the Fontan surgery and that supports a relationship between PHEO and systemic hypoxia.