Biochemical Diagnosis of Phaeochromocytoma and Paraganglioma in Children and Adolescents: A Retrospective Cohort Study.

Introduction: Currently, it is unclear whether plasma free or 24-h urinary fractionated metanephrines are preferable for diagnosis of phaeochromocytoma/paraganglioma (PPGL) in children.

Objectives: To investigate whether measurements of plasma free and 24-h urinary fractionated metanephrines are reliable tests for screening for PPGL in children.

Methods: This retrospective study included a cohort of 138 paediatric patients (5 to 18 years), 64 with and 74 without PPGL. Data included sex, age, plasma concentrations of free metanephrines, and genetic test results. For a subset of 89 children tested for PPGL, concentrations of 24-h urinary fractionated metanephrines were also available. For patients with PPGL, data also included tumour location, size, catecholamine tumour phenotype, and presence of recurrent and/or metastatic disease.

Results: Among children with PPGL, results of plasma metanephrines showed larger fold increases of normetanephrine above the upper cut-off compared to the urinary metabolites (9.5-fold vs 7.1-fold, p < 0.001). Plasma metanephrines showed a diagnostic sensitivity of 92% and specificity of 96%, whereas for urinary metanephrines sensitivity and specificity of 92% and 91% respectively. Sub-analysis of intra-individual temporal measurements of metabolites showed that subsequent increases of plasma normetanephrine may be associated with early-stage development of a noradrenergic PPGL.

Conclusions: Plasma free and 24-h urinary fractionated metanephrines are both reliable screening tests for PPGL in children and adolescents. The plasma panel may be useful for early detection of noradrenergic PPGL relevant for children tested within surveillance programs due to hereditary risk of noradrenergic tumours.