Overnight/first morning urine free metanephrines and methoxytyramine for diagnosis of pheochromocytoma and paraganglioma: Is this an option?

Mirko Peitzsch, Denise Kaden, Christina Pamporaki, Katharina Langton, Georgiana Constantinescu, Catleen Conrad, Stephanie Fliedner, Richard O Sinnott, Aleksander Prejbisz, Roland Därr, Jacques Wm Lenders, Michael Bursztyn (+1 others)
2020 European Journal of Endocrinology  
Objective: Sympathoadrenal activity is decreased during overnight rest. This study assessed whether urinary free normetanephrine, metanephrine and methoxytyramine in overnight/first-morning urine collections might offer an alternative to measurements in 24-hour collections or plasma for diagnosis of pheochromocytoma and paraganglioma (PPGL). Design and methods: Prospective multicenter cross-sectional diagnostic study involving 706 patients tested for PPGL among whom tumors were confirmed in 79
more » ... nd excluded in 627 after follow-up. Another 335 age- and sex-matched volunteers were included for reference purposes. Catecholamines and their free O-methylated metabolites were measured in 24-hour collections divided according to waking and sleeping hours and normalized to creatinine. Plasma metabolites from blood sampled after supine rest were measured for comparison. Results: Urinary outputs of norepinephrine, normetanephrine, epinephrine and metanephrine in the reference population were respectively 50[48-52]%, 35%[32-37]%, 76[74-78]% and 15[12-17]% lower following overnight than daytime collections. Patients in whom PPGLs were excluded showed 28[26-30]% and 6[3-9]% day-to-night falls in normetanephrine and metanephrine while patients with PPGLs showed no significant day-to-night falls in metabolites. Urinary methoxytyramine was consistently unchanged from day-to-night. According to receiver-operating characteristic curves, diagnostic accuracy of metabolite measurements in overnight/first morning urine samples did not differ from measurements in 24-hour urine collections, but was lower for both than for plasma. Using optimized reference intervals, diagnostic specificity was higher for overnight than daytime collections at similar sensitivities. Conclusions: Measurements of urinary free catecholamine metabolites in first morning/overnight urine collections offer an alternative for diagnosis of PPGL to 24-hour collections but remain less accurate than plasma measurements.
doi:10.1530/eje-19-1016 pmid:32187575 fatcat:am4tildh5jdkbe4jxfws33x76e