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J Clin Endocrinol Metab. 2015 Apr;100(4):1325-34. doi: 10.1210/jc.2014-3863. Epub 2015 Jan 12.

Pheochromocytoma and paraganglioma in cyanotic congenital heart disease.

Author information

1
Department of Cardiology (A.R.O., L.E.M., M.J.L., M.N.S., F.W.), Boston Children's Hospital, Boston, Massachusetts 02115; Division of Cardiovascular Medicine, (A.R.O., M.J.L., M.N.S., F.W.), Division of Endocrinology (A.V.), Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts 02115; Department of Medicine (J.Gi., M.R.), Columbia University Medical Center, New York, New York 10027; Adult Congenital Heart Disease Program (M.G.), University Hospital Zurich, CH-8032 Zurich, Switzerland; Department of Medicine (J.A.,A.H.), Division of Cardiology, University of California, Los Angeles, Medical Center, Ahmanson/UCLA Adult Congenital Heart Disease Center, Los Angeles, California 90095; Department of Cardiology (Y.K., L.X.D.), The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104; Department of Medicine (Y.K., L.X.D.), Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19104; Division of Cardiology (J.Gr.), St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4; The Heart Center (A.N.Z.), Nationwide Children's Hospital, Columbus, Ohio 43205; Department of Internal Medicine (A.N.Z.), The Ohio State University Wexner Medical Center, Columbus, Ohio 43210; Department of Medicine (G.A., E.O.), University Health Network and University of Toronto, Toronto, Ontario, CanadaM5G2C4; Department of Pediatrics (M.E.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226; Center for Adrenal Disorders (A.V.), Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts 02115.

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.

PMID:
25581599
PMCID:
PMC4399286
DOI:
10.1210/jc.2014-3863
[Indexed for MEDLINE]
Free PMC Article

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