Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas.
BACKGROUND
Pheochromocytomas and paragangliomas (PPGLs) in children are often hereditary and may present with different characteristics compared with adults. Hereditary PPGLs can be separated into cluster 1 and cluster 2 tumors due to mutations impacting hypoxia and kinase receptor signaling pathways, respectively.


OBJECTIVE
To identify differences in presentation of PPGLs between children and adults.


METHODS
A retrospective cross-sectional clinical study.


METHODS
Seven tertiary medical centers.


METHODS
The study included 748 patients with PPGLs, including 95 with a first presentation during childhood. Genetic testing was available in 611 patients. Other data included locations of primary tumors, presence of recurrent or metastatic disease, and plasma concentrations of metanephrines and 3-methoxytyramine.


RESULTS
Children showed higher (P < 0.0001) prevalence than adults of hereditary (80.4% vs 52.6%), extra-adrenal (66.3% vs 35.1%), multifocal (32.6% vs 13.5%), metastatic (49.5% vs 29.1%), and recurrent (29.5% vs 14.2%) PPGLs. Tumors due to cluster 1 mutations were more prevalent among children than adults (76.1% vs 39.3%; P < 0.0001), and this paralleled a higher prevalence of noradrenergic tumors, characterized by relative lack of increased plasma metanephrine, in children than in adults (93.2% vs 57.3%; P < 0.0001).


CONCLUSIONS
The higher prevalence of hereditary, extra-adrenal, multifocal, and metastatic PPGLs in children than adults represents interrelated features that, in part, reflect the lower age of disease presentation of noradrenergic cluster 1 than adrenergic cluster 2 tumors. The differences in disease presentation are important to consider in children at risk for PPGLs due to a known mutation or previous history of tumor.
Departments of Medicine ??I and.
Christina
C
Pamporaki
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2425.
Barbora
B
Hamplova
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the TU Dresden, D-01307 Dresden, Germany.
Mirko
M
Peitzsch
Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland.
Aleksander
A
Prejbisz
Department of Medicine IV, University Hospital of Munich, 80539 Munich, Germany.
Felix
F
Beuschlein
Department of Internal Medicine, Radboud University Medical Centre, 6525 HP Nijmegen, The Netherlands.
Henri J L M
HJLM
Timmers
Department of Internal Medicine, Division of Endocrinology, University Hospital, University of Wuerzburg, 97070 Wuerzburg, Germany.
Martin
M
Fassnacht
Institute for Clinical Genetics, Faculty of Medicine Carl Gustav Carus at the TU Dresden, D-01307 Dresden, Germany.|German Cancer Consortium, D-01307 Dresden, Germany.|German Cancer Research Center, 69120 Heidelberg, Germany.|National Center for Tumor Diseases, D-01307 Dresden, Germany.
Barbara
B
Klink
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2425.
Maya
M
Lodish
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2425.
Constantine A
CA
Stratakis
Pediatrics, and.
Angela
A
Huebner
Department of Medicine, University Medical Center Schleswig-Holstein, 23562 Luebeck, Germany.
Stephanie
S
Fliedner
Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre, 28029 Madrid, Spain.
Mercedes
M
Robledo
Department of Computing and Information, University of Melbourne, 3010 Melbourne, Australia.
Richard O
RO
Sinnott
Department of Hypertension, Institute of Cardiology, 04-628 Warsaw, Poland.
Andrzej
A
Januszewicz
The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2425.
Karel
K
Pacak
Departments of Medicine ΙΙI and.|Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the TU Dresden, D-01307 Dresden, Germany.
Graeme
G
Eisenhofer
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D000328:Adult; D017668:Age of Onset; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000235:genetics; D010235:Paraganglioma / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D010673:Pheochromocytoma / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D015995:Prevalence; D012189:Retrospective Studies