Plasma metanephrines responses to adreno-sympathetic stress

Abstract

Background: Plasma metanephrines measurement is a highly sensitive method for the diagnosis of catecholamine producing tumors. Pre-analytical factors such as non specific adrenosympathetic stimulations may alter the specificity of the test. Methods: Free catecholamines and metanephrines were determined in plasma after three adrenosympathetic stimulations: postural change from supine to standing position, insulin-induced hypoglycaemia test and a cold pressure test. Results: Sympatho-neuronal stimulation such as orthostatic stimulation and cold exposure mainly stimulated the release of norepinephrine (+61% and +34%, respectively) and in a weaker way of adrenaline (+28% and +16%, respectively). The resulting rise in normetanephrine and metanephrine is much more attenuated after orthostatic change (+30% and +22%, respectively) and cold exposure (+19% without change for metanephrine). Insulin-induced hypoglycaemia elicited a massive release of epinephrine from the adrenal medulla (+1587 %) and to a lesser extent that of norepinephrine from sympathetic neurons (+134%). Plasma normetanephrine and metanephrine peaked 15 minutes later and peaks were more attenuated (+375% and +58%, respectively). Plasma concentrations exceeded the threshold of the paragangliome detection test in 15% of patients for normetanephrine after orthostatic stimulation and 76% of patients for metanephrine after hypoglycemic stress. Conclusion: A moderate sympatho-excitatory stimulation such as exposure to cold has little influence on plasma metanephrines. In contrast, postural changes and metabolic stresses can lead to falsely positive interpretations of the detection test confirming the requirement of blood sampling after at least 30 minutes of rest in supine position.