Endocrine Abstracts

Background: Measurements of plasma metanephrines provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma (PPGL). However, false positive results can pose a diagnostic dilemma for clinicians. The aim of the study was to determine whether commonly prescribed drugs with potential action on the sympathetic nervous system can falsely elevate plasma free normetanephrine, metanephrine and methoxytyramine.

Methods: This retrospective study included 461 patients among who PPGL was excluded. Data on sex, age, plasma free normetanephrine, metanephrine and methoxytyramine concentrations, cardiometabolic comorbidities and/or seriouschronic illness (CCI), as well as a listing of all medications taken at the time of testingwere collected. Measurements of metabolites were by liquid chromatography with tandem mass spectrometry. For four patients under treatment with tricyclic antidepressants and/or serotonin-norepinephrine-reuptake blockers (NRBs), metabolites were measured at baseline and after discontinuation of the drug for at least five days.

Results: Among 461 patients, 408 were treated with various medications, including 23 with NRBs, 14 with selective-serotonin-reuptake-blockers, five with atypical antipsychotics, ten with anticonvulsants, 19 with hypnotics, 175 with diuretics, 187 with beta-blockers, 189 with dihydropyridines, 18 with non-dihydropyridines, 121 with angiotensin-converting-enzyme-inhibitors, 172 with angiotensin-receptor-blockers, 64 with alpha-blockers, 64 with central-agonists, 14 with vasodilators, and five with renin-inhibitors. Among 369 patients under antihypertensive treatment, 278 were treated with more than one antihypertensive drug. Rates of false positive results for plasma free normetanephrine, metanephrine and methoxytyramine in the entire cohort were 6% (29/461), 1% (4/461) and 1% (5/461) respectively. NRBs were responsible for 10% and 40% of all false positive elevations of normetanephrine and methoxytyramine respectively, whereas treatment with multiple antihypertensive drugs for 59% and 60% respectively. Nevertheless, for the vast majority of patients with multiple antihypertensive drugs and false positive elevations of normetanephrine(12/17), CCI were reported. Multivariable regression analysis after controlling for age, sex and the presence of CCI, indicated that only NRBs have significant impact on plasma free normetanephrine concentrations (P=0.0014). Among four patients under NRBs with paired metabolite measurements before and after discontinuation of treatment, all showed drops of normetanephrine levels below upper-cut offs after discontinuation of the medication, whereas for methoxytyramine all but one.

Conlcusion: Plasma free metanephrines and methoxytyramine is a test with a low rate of false positive results. Apart from NRBs, other medications have negligible impact on false positive results for plasma free normetanephrine.