Faculty Collaboration Database

Pheochromocytoma and paraganglioma in cyanotic congenital heart disease. J Clin Endocrinol Metab 2015 Apr;100(4):1325-34

Date

01/13/2015

Pubmed ID

25581599

Pubmed Central ID

PMC4399286

DOI

10.1210/jc.2014-3863

Scopus ID

2-s2.0-84927617390 (requires institutional sign-in at Scopus site)   83 Citations

Abstract

CONTEXT: Aberrant cellular oxygen sensing is a leading theory for development of pheochromocytoma (PHEO) and paraganglioma (PGL).

OBJECTIVE: The objective of the study was to test the hypothesis that chronic hypoxia in patients with cyanotic congenital heart disease (CCHD) increases the risk for PHEO-PGL.

DESIGN/SETTING/PARTICIPANTS: We investigated the association between CCHD and PHEO-PGL with two complementary studies: study 1) an international consortium was established to identify congenital heart disease (CHD) patients with a PHEO-PGL diagnosis confirmed by pathology or biochemistry and imaging; study 2) the 2000-2009 Nationwide Inpatient Survey, a nationally representative discharge database, was used to determine population-based cross-sectional PHEO-PGL frequency in hospitalized CCHD patients compared with noncyanotic CHD and those without CHD using multivariable logistic regression adjusted for age, sex, and genetic PHEO-PGL syndromes.

RESULTS: In study 1, we identified 20 PHEO-PGL cases, of which 18 had CCHD. Most presented with cardiovascular or psychiatric symptoms. Median cyanosis duration for the CCHD PHEO-PGL cases was 20 years (range 1-57 y). Cases were young at diagnosis (median 31.5 y, range 15-57 y) and 7 of 18 had multiple tumors (two bilateral PHEO; six multifocal or recurrent PGL), whereas 11 had single tumors (seven PHEO; four PGL). PGLs were abdominal (13 of 17) or head/neck (4 of 17). Cases displayed a noradrenergic biochemical phenotype similar to reported hypoxia-related PHEO-PGL genetic syndromes but without clinical signs of such syndromes. In study 2, hospitalized CCHD patients had an increased likelihood of PHEO-PGL (adjusted odds ratio 6.0, 95% confidence interval 2.6-13.7, P < .0001) compared with those without CHD; patients with noncyanotic CHD had no increased risk (odds ratio 0.9, P = .48).

CONCLUSIONS: There is a strong link between CCHD and PHEO-PGL. Whether these rare diseases coassociate due to hypoxic stress, common genetic or developmental factors, or some combination requires further investigation.

Author List

Opotowsky AR, Moko LE, Ginns J, Rosenbaum M, Greutmann M, Aboulhosn J, Hageman A, Kim Y, Deng LX, Grewal J, Zaidi AN, Almansoori G, Oechslin E, Earing M, Landzberg MJ, Singh MN, Wu F, Vaidya A

MESH terms used to index this publication - Major topics in bold

Adolescent
Adrenal Gland Neoplasms
Adult
Cross-Sectional Studies
Cyanosis
Female
Heart Defects, Congenital
Humans
Male
Middle Aged
Paraganglioma
Pheochromocytoma
Retrospective Studies
Young Adult