A Case of Malignant Pheochromocytoma with Holt-Oram Syndrome

Abstract

Abstract.A 23-year-old female patient with malignant pheochromocytoma was admitted to the Tokyo Women's Medical University. The patient had been clinically diagnosed with Holt-Oram syndrome at birth. Since she had complex congenital heart disease, chronic heart failure, and severe hypoxia, the risk surrounding surgery to remove the primary tumor was predicted to be very high, and subsequently, chemotherapy was performed. The patient was not able to continue chemotherapy due to adverse effects. However, for one year, both her hypertension and catecholaminedependent symptoms were well controlled by an alpha-adrenergic and beta-adrenergic receptor blockade, although the patient did experience high plasma norepinephrine levels. To our knowledge, this is the first report of a patient with the combination of malignant pheochromocytoma and Holt-Oram syndrome. A correlation between chronic hypoxia and pheochromocytoma has been reported. This instructive case reminds us to consider the possibility of pheochromocytoma with congenital heart disease when these types of unexpected or unusual symptoms are encountered.

Pheochromocytoma and paraganglioma in Fontan patients: Common more than expected

“…In one patient with moderate hypoxemia, PHEO was advanced with metastasis to multiple sites, including bone and liver. Malignant PHEO is rare, but which was also reported in the cyanotic CHD previously . Since PHEO/PGL has the potential of malignant transformation, early detection is crucial.…”

“…PHEO is rare, but which was also reported in the cyanotic CHD previously. 10 Since PHEO/PGL has the potential of malignant transformation, early detection is crucial.…”

Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas

“…In this setting, PCC/PGL can be single or multiple, benign or malignant, and these patients may also present with acquired polycythemia, secondary to chronic hypoxia [Yoshihara et al, 2008;Subedi and Judson, 2014]. In addition to the chronic hypoxic stimulus, PCC/PGL may develop in these patients due to abnormalities in genes responsible for the function of neural crest cells, which could be involved in both PCC/ PGL and the formation of the heart outflow tracts [Kita et al, 2003].…”

“…In summary, sustained severe hypoxia can lead to autonomous nervous system and endocrine hyperactivity, as well as mitogenic stimulation [Kita et al, 2003;Douwes Dekker et al, 2007;Yoshihara et al, 2008]. As a consequence, carotid body chief cell and chromaffin cell hyperplasia is promoted and HIF is abnormally stabilized, allowing the development of PCC/PGL [Diez et al, 1999;Subedi and Judson, 2014].…”

Pheochromocytoma complicated by cyanotic congenital heart disease: a case report

“…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 ).…”