Endocrine Abstracts (2009) 20 P31

Confounding variables for plasma metanephrines and normetanephrines may influence the diagnosis of pheochromocytomas

Timo Deutschbein, Andrea Jäger, Klaus Mann & Stephan Petersenn


Division of Endocrinology, University of Duisburg-Essen, Essen, NRW, Germany.


Introduction: Measurements of plasma metanephrines (META) and normetanephrines (NOR) have been advocated as first-line tests for the diagnosis of pheochromocytoma. This study assessed the impact of several potential confounders, which may influence the correct diagnosis.

Methods: Eight healthy males (age 26.8±1.7; BMI 23.1±0.8) were tested on 6 separate days. Tests were performed in supine rest with blood sampling via i.v. canullas at 0900 h following an overnight fast. Samples were taken after venipuncture (0,15,30,60,90,120′), after caffeine (0,60′), after standard breakfast (0,60′), after physical exercise (0,15,30′), and in various body positions (upright and lying each 0,120′). Samples were centrifuged and frozen directly after collection. In addition, whole-blood and plasma samples were stored either at 4°C or at room temperature (RT) for 0, 1, 3, 24, and 72 h. Plasma META and NOR were measured by RIA (LDN, Nordhorn, Germany).

Results: META and NOR were not significantly influenced by venipuncture. Caffeine (+23%) and food (+8%) elevated NOR significantly (P<0.05), while META remained stable. Physical exercise increased META (+82%) and NOR (+84%) significantly (P<0.005). Lying posture significantly decreased both META (−34%) and NOR (−19%) compared to standing position (P<0.01). In plasma, META and NOR were stable at 4°C for 72 h, but decreased significantly, when stored at RT. In whole-blood, NOR were significantly increased after 72 h, both at 4°C and at RT.

Conclusion: Blood samples for determination of META and NOR should be immediately centrifuged and stored at 4°C to improve stability. Interestingly, levels of NOR increased in whole-blood, potentially due to ongoing enzymatic activity. Food, caffeine, and physical exercise should be avoided prior to sampling. Samples should be taken in a standardized posture. Significant changes due to confounders may lead to a misdiagnosis of pheochromocytomas.

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