Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. The aim of the study was to establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methoxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

Abstract Background Diagnosis of pheochromocytomas and paragangliomas in patients receiving hemodialysis is troublesome. Aim To establish optimal conditions for blood sampling for mass spectrometric measurements of normetanephrine, metanephrine and 3-methoxytyramine in patients on hemodialysis and specific reference intervals for plasma metanephrines under the most optimal sampling conditions. Methods Blood was sampled before and near the end of dialysis, including different sampling sites in 170 patients on hemodialysis. Results Plasma normetanephrine concentrations were lower (P < 0.0001) and metanephrine concentrations higher (P < 0.0001) in shunt than in venous blood, with no differences for 3-methyxytyramine. Normetanephrine, metanephrine and 3-methoxytyramine concentrations in shunt and venous blood were lower (P < 0.0001) near the end than before hemodialysis. Upper cut-offs for normetanephrine were 34% lower when the blood was drawn from the shunt and near the end of hemodialysis compared to blood drawn before hemodialysis. Conclusion This study establishes optimal sampling conditions using blood from the dialysis shunt near the end of hemodialysis with optimal reference intervals for plasma metanephrines for the diagnosis of pheochromocytomas/paragangliomas among patients on hemodialysis.

To the Editor: The diagnostic work-up of pheochromocytoma/paraganglioma (PPGL) among patients with chronic kidney disease (CKD) is a clinical challenge. Impaired renal elimination of catecholamines and their metabolites confounds urinary tests, while increased plasma concentrations of free metanephrines in patients with CKD also complicate interpretation of plasma tests.1, 2, 3 We therefore aimed to establish optimal reference intervals for plasma free metanephrines and 3-methoxytyramine in patients with CKD stages 3 and 4 or receiving hemodialysis (HD).This prospective multicenter study included 234 patients (79 CKD3, 48 CKD4, and 107 receiving HD) and an aged-matched reference population of 173 individuals (Table 1; Item S1). Measurements of plasma free normetanephrine, metanephrine, and 3-methoxytyramine were performed using liquid chromatography–tandem mass spectrometry (LC-MS/MS).4