Pheochromocytoma and paraganglioma in Fontan patients: Common more than expected

Song, Mi Kyoung; Kim, Jun Seok; Bae, Eun Jung; Lee, Young Ah; Kim, Ho; Min, Sang Il; Kim, Jung Hee; Won, Jae Kyung

doi:10.1111/chd.12625

Cited by 21 publications

(19 citation statements)

References 25 publications

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“…They developed gastrointestinal and pancreatic neuroendocrine tumors (NETs), the first to our knowledge. These cases now join the other NETs, pheochromocytomas and paragangliomas, previously reported in this patient population [5] .…”

Section: Introductionsupporting

confidence: 84%

“…This series included 5 cases and 2 of these patients were children [6] . In a more recent study of 283 Fontan patients, Song, et al, reported 3 cases of pheochromocytomas and 4 paragangliomas with 3 of the 7 patients 18 years of age or younger [5] . Three of these patients were clinically asymptomatic, while 4 had symptoms such as hypertension, headache and palpitations.…”

Section: Discussionmentioning

confidence: 99%

“…This hypothesis is supported by the fact that genetic factors associated with increased incidence of NETs such as succinate dehydrogenase complex mutations and von Hippel Landau are associated with activation of the hypoxia inducible factor. Mutations in the hypoxia pathway are manifested by a noradrenergic phenotype (elevated norepinephrine and metanephrines) and absence of adrenergic phenotype (normal epinephrine and metanephrines) [5] . Folger et al, also postulated that a state of chronic hypoxia may result in adrenal medullary hyperplasia and increased incidence of adrenal tumors [4] .…”

Section: Discussionmentioning

confidence: 99%

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Gastrointestinal neuroendocrine tumors in Fontan patients

Vural

Skaria

Dehner

et al. 2020

Radiology Case Reports

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The Fontan procedure used for palliation of single ventricle physiology is associated with multisystemic morbidity. With improving survival and increased use of surveillance imaging in this patient population, long-term complications associated with Fontan circuits are commonly encountered by radiologists. One interesting observation is the apparent increased risk of paragangliomas and pheochromocytomas in this group of patients and perhaps a pathogenetic role of chronic hypoxia. We report 2 cases of gastrointestinal neuroendocrine tumors (NET) in the setting of Fontan circuit. The first is a 20-year-old female with history of hypoplastic left heart and Fontan palliation who presented with hematochezia and was diagnosed with a jejunal grade 2 NET. The second case is of a 12-year-old boy with history Fontan palliation for single ventricle physiology, incidentally found to have a well-differentiated pancreatic NET during precardiac transplant workup. These cases should alert the radiologists to be aware of the apparent association between Fontan procedure and NET.

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Section: Introductionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Gastrointestinal neuroendocrine tumors in Fontan patients

Vural

Skaria

Dehner

et al. 2020

Radiology Case Reports

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“…The coexistence of CHD and P-PGL has already been reported in previous studies and a causal link between the two conditions has been postulated [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 82%

Pheochromocytoma in Congenital Cyanotic Heart Disease

Aresta

Butera

Tufano

et al. 2018

Case Reports in Endocrinology

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Studies on genome-wide transcription patterns have shown that many genetic alterations implicated in pheochromocytoma-paraganglioma (P-PGL) syndromes cluster in a common cellular pathway leading to aberrant activation of molecular response to hypoxia in normoxic conditions (the pseudohypoxia hypothesis). Several cases of P-PGL have been reported in patients with cyanotic congenital heart disease (CCHD). Patients affected with CCHD have an increased likelihood of P-PGL compared to those affected with noncyanotic congenital heart disease. One widely supported hypothesis is that chronic hypoxia represents the determining factor supporting this increased risk. We report the case of a 23-year-old woman affected with congenital tricuspid atresia surgically by the Fontan procedure. The patient was admitted to hospital with hypertensive crisis and dyspnea. Chest computed tomography revealed, incidentally, a 6-cm mass in the left adrenal lodge. Increased levels of noradrenaline (NA) and its metabolites were detected (plasma NA 5003.7 pg/ml, n.v.<480; urinary NA 1059.5 µg/24 h, n.v.<85.5; urinary metanephrine 489 µg/24 h, n.v.<320). The patient did not report any additional symptom related to catecholamine excess. The left adrenal tumor showed abnormal accumulation when 131I-metaiodobenzylguanidine scintigraphy was performed. A 18F-fluorodeoxyglucose positron emission tomography showed no significant metabolic activity in the left adrenal gland but intense uptake in the supra- and subdiaphragmatic brown adipose tissue, probably due to noradrenergic-stimulated glucose uptake. The patient underwent left open adrenalectomy after preconditioning with α- and β-blockers and histopathological examination confirmed the diagnosis of pheochromocytoma (Ki-67<5%). Screening for germline mutations did not show any genes mutation (investigated mutations: RET, TMEM127, MAX, SDHD, SDHC, SDHB, SDHAF2, SDHA, and VHL). Clinicians should consider P-PGL when an unexplained clinical deterioration occurs in CCHD patients, even in the absence of typical paroxysmal symptoms.

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“…However, 3 of those 21 (14%) patients had a history of a cyanotic heart disease, which was unlikely to be an incidental occurrence [9]. A recent study from Korea showed that the incidence of PPGL among Fontan patients older than 10 years of age was 2.5%, which is almost fourfold higher than the general population [10]. The age of onset in these patients was also significantly earlier compared with those with no history of congenital heart disease (CHD).…”

Section: Prevalence Of Ppgl In Patients With Cchdmentioning

confidence: 99%

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

Agarwal

Jindal

Balázs

et al. 2019

Journal of the Endocrine Society

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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.

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Pheochromocytoma and paraganglioma in Fontan patients: Common more than expected

Cited by 21 publications

References 25 publications

Gastrointestinal neuroendocrine tumors in Fontan patients

Gastrointestinal neuroendocrine tumors in Fontan patients

Pheochromocytoma in Congenital Cyanotic Heart Disease

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

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