Seasonal variation in plasma free normetanephrine concentrations: implications for biochemical diagnosis of pheochromocytoma.
BACKGROUND
Higher plasma concentrations of catecholamines in winter than in summer have been established, but whether this impacts the plasma concentrations of metanephrines used for the diagnosis of pheochromocytoma is unknown.


OBJECTIVE
In this study, we examined seasonal variations in the 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
The measurements of the 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 the 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, the 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 (P=0.0012) 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 (P=0.0010). Forearm warming increased blood flow and lowered (P=0.0020) plasma normetanephrine concentrations.


CONCLUSIONS
The 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.
Christina
C
Pamporaki
Michael
M
Bursztyn
Manja
M
Reimann
Tjalf
T
Ziemssen
Stefan R
SR
Bornstein
Fred C G J
FC
Sweep
Henri
H
Timmers
Jacques W M
JW
Lenders
Graeme
G
Eisenhofer
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D005542:Forearm / Q000098:blood supply; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008676:Metanephrine / Q000097:blood*; D008875:Middle Aged; D009647:Normetanephrine / Q000097:blood*; D010673:Pheochromocytoma / Q000097:blood / Q000175:diagnosis*; D012039:Regional Blood Flow; D012621:Seasons
D009647:Normetanephrine; D008676:Metanephrine