Seasonal variation in plasma free normetanephrine concentrations: implications for biochemical diagnosis of pheochromocytoma

Abstract

Background: Higher plasma concentrations of catecholamines in winter than in summer are established; whether this impacts plasma concentrations of metanephrines used for the diagnosis of pheochromocytoma is unknown. Objective: In this study, we examined seasonal variations in plasma concentrations of metanephrines, the impact of this on diagnostic test performance and the influences of forearm warming ('arterialization' of venous blood) on blood flow and measured concentrations. Methods: Measurements of plasma concentrations of metanephrines were recorded from 4052 patients tested for pheochromocytoma at two clinical centers. Among these patients, 107 had tumors. An additional 26 volunteers were enrolled for measurements of plasma metanephrines and forearm blood flow before and after forearm warming. Results: There was no seasonal variation in the plasma concentrations of metanephrines among patients with pheochromocytoma, whereas among those without tumors, plasma concentrations of normetanephrine were higher (P!0.0001) in winter than in summer. Lowest concentrations of normetanephrine were measured in July, with those recorded from December to April being more than 21% higher (P!0.0001). These differences resulted in a twofold higher (PZ0.0012) prevalence of false-positive elevations of normetanephrine concentrations in winter than in summer, associated with a drop in overall diagnostic specificity from 96% in summer to 92% in winter (PZ0.0010). Forearm warming increased blood flow and lowered (PZ0.0020) plasma normetanephrine concentrations. Conclusions: Plasma concentrations of normetanephrine are subject to seasonal variation with a resulting higher prevalence of false-positive results in winter than in summer. Lowered plasma concentrations of normetanephrine with forearm warming suggest an effect of temperature. These results have implications for considerations of temperature to minimize false-positive results.

Mass spectrometric quantification of salivary metanephrines—A study in healthy subjects

“…2014), previous adrenalectomy (Osinga et al . 2013) and even the season of the year (Pamporaki et al . 2014).…”

Effects of Gut Bacteria Depletion and High‐Na+ and Low‐K+ Intake on Circulating Levels of Biogenic Amines

“…A separate assay using HPLC showed that plasma norepinephrine levels were altered neither by the diet nor by antibiotic treatment (data not shown), suggesting the effects on normetanephrine were due to changes in norepinephrine metabolism to normetanephrine rather than in plasma levels of its precursor norepinephrine. Seasonal variation in plasma normetanephrine levels were reported . Although this variation was small (i.e., 21% higher in winter than in summer), it resulted in a twofold higher prevalence of false‐positive elevations of normetanephrine in winter than in summer.…”

“…Normetanephrine is an O‐methylated metabolite of norepinephrine, used for the diagnosis of pheochromocytoma that secrets large amounts of catecholamines, mostly norepinephrine. It is interesting to find that plasma normetanephrine was depleted after antibiotic treatment, suggesting the intriguing possibility that the production of this metabolite from norepinephrine may entirely depend on gut bacteria.…”

Seasonal variations of plasma normetanephrine levels in Los Angeles

“…We read with great interest the paper 'Seasonal variation in plasma free normetanephrine concentrations: implications for biochemical diagnosis of pheochromocytoma' published in the March 2014 issue of the European Journal of Endocrinology (1). In that paper, the authors describe w20% higher levels of plasma normetanephrine, a biochemical marker of pheochromocytoma, in the winter, in two cities with northern temperate climate.…”