Preanalytical considerations and out-patient vs in-patient tests of plasma metanephrines to diagnose pheochromocytoma

Context: Sampling of blood in the supine position for diagnosis of pheochromocytoma and paraganglioma (PPGL) results in lower rates of false-positives for plasma normetanephrine than seated sampling. It is unclear how in-patient versus out-patient testing and other preanalytical factors impact false-positives. Objective: Identify preanalytical precautions to minimize false-positive results for plasma metanephrines. Design: Impacts of different blood sampling conditions on plasma metanephrines were evaluated, including out-patient versus in-patient testing, sampling of blood in semi- versus fully recumbent positions, use of cannulae versus direct venipuncture and differences in outside temperature. Setting: Ten tertiary referral centers. Patients: 3147 patients tested for PPGL, including 278 with and 2869 without tumors. Interventions: None. Outcome measures: Plasma metanephrines and rates of false-positive results. Results: Out-patient rather than in-patient sampling resulted in 44% higher plasma concentrations and a 3.4-fold increase in false-positive results for normetanephrine. Low temperature, a semi-recumbent position and direct venipuncture also resulted in significantly higher plasma concentrations and rates of false-positive results for plasma normetanephrine than alternative sampling conditions, though with less impact than out-patient sampling. Higher concentrations and rates of false-positive results for plasma normetanephrine with low than warm temperatures were only apparent for out-patient sampling. Preanalytical factors were without impact on plasma metanephrines in patients with PPGL. Conclusions: Although in-patient blood sampling is largely impractical for screening patients with suspected PPGL, other pre-analytical precautions (e.g., cannulae, warm testing conditions) may be useful. In-patient sampling may be reserved for follow-up of patients with difficult to distinguish true- from false-positive results.