Measurements of plasma metanephrines and
methoxytyramine provide a sensitive test for diagnosis of
pheochromocytoma/
paraganglioma. False-positive results remain a problem, particularly in patients taking
norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and
methoxytyramine in 61 patients taking
norepinephrine reuptake blockers (
tricyclic antidepressants or
serotonin-
norepinephrine reuptake inhibitors) and 17 others taking
selective serotonin reuptake inhibitors, all without
pheochromocytoma/
paraganglioma. We highlight a singular case with strongly elevated plasma
normetanephrine and
methoxytyramine concentrations associated with
norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without
tumors. Plasma
normetanephrine was 40% higher (P < 0.0001) in patients on
norepinephrine reuptake blockers and
methoxytyramine was 127% higher (P = 0.0062) in patients taking
tricyclic antidepressants compared to patients not taking uptake blockers and without
tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for
normetanephrine and from 0.9% to 28.6% for
methoxytyramine.
Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma
normetanephrine and
methoxytyramine were elevated more than six times above upper reference limits. A
pheochromocytoma/
paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of
norepinephrine reuptake blockers. These findings clarify that
norepinephrine reuptake blockers usually result in mild elevations of
normetanephrine and
methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in
normetanephrine and
methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the
norepinephrine reuptake blockade.