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DOI: 10.1055/s-0034-1371997
Seasonal variation of plasma free normetanephrine concentrations: implications for biochemical diagnosis of pheochromocytoma
Background: Higher concentrations of plasma catecholamines in winter than summer are established, but whether this impacts plasma concentrations of metanephrines used for diagnosis of pheochromocytoma is unknown.
Objective: We examined seasonal variations in plasma concentrations of metanephrines, the impact of this on diagnostic test performance and influences of forearm warming (“arterialization” of venous blood) on blood flow and measured concentrations.
Methods: Measurements of plasma metanephrines were recorded from 4052 patients tested for pheochromocytoma at two clinical centers. Among these 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 plasma metanephrines among patients with pheochromocytoma, whereas for those without tumors plasma concentrations of normetanephrine were higher (P < 0.0001) in winter than in summer. Lowest normetanephrine levels were measured in July, with those recorded in December to April being more than 21% higher (P < 0.0001). These differences resulted in a 2-fold higher (P = 0.0012) prevalence of false-positive elevations of normetanephrine in winter than in summer, associated with a drop in overall diagnostic specificity from 96% in summer to 92% in winter (P = 0.0010). Warming of the forearm increased blood flow and lowered (P = 0.0020) 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 summer. Lowered plasma normetanephrine concentrations with forearm warming suggest a temperature effect. These results have implications for considerations of temperature to minimize false-positive results.