Endocrine Abstracts (2011) 26 S24.1

Biochemical screening for phaeochromocytoma using plasma free metanephrines: utility beyond diagnosis

G Eisenhofer


Technische Universität Dresden, Dresden, Germany.


Measurements of plasma concentrations of the O-methylated metabolites of catecholamines including metanephrine, normetanephrine and methoxytyramine have advantages over other biochemical tests used to diagnose phaeochromocytoma for several reasons: i) the metabolites are produced within chromaffin cells continuously from catecholamines leaking from storage vesicles; ii) the single largest source of these metabolites is from adrenal medullary chromaffin cells, but this production normally represents a minor pathway of catecholamine metabolism; iii) in phaeochromocytoma tumour cells the O-methylation pathway dominates; iv) intra-tumoural production of the metabolites occurs independently of variations in catecholamine release; and v) other catecholamine metabolites, including sulfate-conjugated metanephrines measured in urine, are produced largely downstream of chromaffin tumour cells. The consequences of these influences, as shown using data from 365 patients with phaeochromocytoma, go well beyond utility of the metabolites for diagnosis. Increases in the metabolites can be used to predict tumour size, important for assessing disease burden and response to therapy in patients with malignant disease. Measurements of plasma methoxytyramine also provide a novel biomarker for malignancy and together with succinate dehydrogenase type B subunit mutation status, tumour size and location provide useful information to assess malignant risk. Furthermore, patterns of increases of metanephrine, normetanephrine and methoxytyramine show distinct differences according to hereditary syndrome and thus provide an easily utilised tool to guide cost-effective genotyping of underlying disease-causing mutations. Differences in ages of tumour presentation according to different biochemical phenotypes and tumour locations also suggest origins from different chromaffin progenitor cells with variable susceptibility to disease causing mutations.

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