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Comparative Study
. 2017 Apr 1;102(4):1122-1132.
doi: 10.1210/jc.2016-3829.

Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas

Christina Pamporaki  1 , Barbora Hamplova  2 , Mirko Peitzsch  3 , Aleksander Prejbisz  4 , Felix Beuschlein  5 , Henri J L M Timmers  6 , Martin Fassnacht  7 , Barbara Klink  8   9   10   11 , Maya Lodish  2 , Constantine A Stratakis  2 , Angela Huebner  12 , Stephanie Fliedner  13 , Mercedes Robledo  14 , Richard O Sinnott  15 , Andrzej Januszewicz  4 , Karel Pacak  2 , Graeme Eisenhofer  16   3
Affiliations
Comparative Study

Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas

Christina Pamporaki et al. J Clin Endocrinol Metab. .

Abstract

Context: 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.

Design: A retrospective cross-sectional clinical study.

Setting: Seven tertiary medical centers.

Patients: 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.

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Figures

Figure 1.
Figure 1.
Plasma concentrations of (a) normetanephrine, (b) metanephrine, and (c) methoxytyramine in children and young (<35 years old) and old (>35 years old) adult patients.
Figure 2.
Figure 2.
Biochemical phenotypes of (a) pediatric and adult sporadic, (b) hereditary, and (c) adrenal-located PPGLs. Characterization of PPGLs with and without appreciable epinephrine (EPI) production [adrenergic (EPI) vs noradrenergic (NE) phenotypes] was established according to the scatterplot relationship of plasma concentrations of metanephrine vs increases of plasma metanephrine as a percentage of increases of the summed total of all O-methylated metabolites above reference (Δ metanephrine ratio). The dashed vertical line depicts the upper reference limit (62 mg/mL) used to establish increased vs normal plasma concentrations of metanephrine. The dashed horizontal line depicts the cutoff at 5% used to establish appreciable metanephrine (epinephrine) production according to total production of all O-methylated metabolites.
Figure 3.
Figure 3.
Cumulative frequencies as a function of age in hereditary disease, including (a) tumors due to cluster 1 vs cluster 2 mutations, (b) noradrenergic vs adrenergic tumors, (c) multifocal vs bilateral adrenal tumors, (d) solitary adrenal vs extra-adrenal tumors, (e) metastatic disease vs recurrent nonmetastatic disease, and (f) nonsynchronous vs synchronous metastatic disease.
See this image and copyright information in PMC

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