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.