Plasma metanephrines responses to adreno-sympathetic stress

Abstract

Eric Pussard, Amel Chaouch, Toihiri Said

Background: Plasma metanephrines (MNs) measurement is a highly sensitive method for the diagnosis of catecholamine producing tumors. Pre-analytical factors like non-specific adreno-sympathetic stimulations may alter the specificity of the test. Methods: Free catecholamines and MNs were determined in plasma after three adreno-sympathetic stimulations: Postural change from supine to standing the position, insulininduced hypoglycemia test and a cold pressure test. Results: Sympatho-neuronal stimulation such as orthostatic stimulation and cold exposure mainly stimulated the release of norepinephrine (NE) (+61% and +34%, respectively) and in a weaker way of adrenaline (+28% and +16%, respectively). The resulting rise in normetanephrine (NMN) and MN is much more attenuated after orthostatic change (+30% and +22%, respectively) and cold exposure (+19% without change for MN). Insulin-induced hypoglycemia elicited a massive release of epinephrine from the adrenal medulla (+1587%) and to a lesser extent that of NE from sympathetic neurons (+134%). Plasma NMN and MN peaked 15 min 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 NMN after orthostatic stimulation and 76% of patients for MN after hypoglycemic stress. Conclusion: A moderate sympatho-excitatory stimulation such as exposure to cold has little influence on plasma MNs. 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 min of rest in the supine position.