PSUN28 Factors Associated with False-positive Fractionated Metanephrines in Plasma and Urine

CONTEXT: Plasma and 24-hr urine metanephrine (M) and normetanephrine (NM) are the standard of care tests used in the biochemical diagnosis of pheochromocytoma and paraganglioma (PPGL). Considering the rarity of PPGL, false positive (FP) results represent a challenge because they lead to additional investigations, healthcare burden, and uncertainty for the patient. The impact of medications on the rate of FP results is not fully established. OBJECTIVE: We aimed to identify the medications associated with the FP rate of 24-hr urine and plasma M and NM measured by the HPLC-MS/MS method. METHODS: We conducted a single-center study of patients who had 24-hour urine or plasma M and NM testing between 09/27/2015 and 02/15/2021, and who had a follow-up of at least 6 months. Results were considered FP if M/NM were > upper limit of the normal ranges (ULN) and there was absence of PPGL. Results were considered true negative (TN) when M/NM were within the reference ranges in patients without PPGL. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models. RESULTS: Plasma M/NM testing was performed in 3152 patients and 24-hr urine M/NM was performed in 2008 patients. The FP rate for the M fraction (plasma: 0.8%, urine: 1.3%) was much lower than the FP rate for NM (plasma: 16%, urine: 4.4%); thus, the impact of medications on FP rate was examined only for NM. In those with FP NM, the median degrees of elevation were 24% (IQR 10-46) >ULN in plasma and 26% (IQR 11-45) >ULN in urine. When compared to patients with TN results, patients with FP plasma NM were more likely to be treated with opioids (OR=1.29, 95%CI, 1.04-1.60), tricyclic antidepressants (OR=1.61, 95%CI,1.14-2.27), serotonin–norepinephrine reuptake inhibitors (OR=1.85, 95%CI, 1.35-2.53), second generation antipsychotics (OR=2.32, 95%CI, 1.28-4.20), but not first generation antipsychotics (OR=1.23, 95% CI, 0.86-1.75) when compared to the TN group. When compared to patients with TN results, patients with FP urine NM were more likely to be treated with opioids (OR=1.96 95%CI, 1.26-3.06), tricyclic antidepressants (OR=2.61, 95%CI, 1.47-4.65), serotonin–norepinephrine reuptake inhibitors (OR=2.20, 95%CI, 1.20-4.02), and both first (OR=3.06, 95%CI, 1.74-5.38) and second generation antipsychotics (OR=2.51, 95%CI, 1.03-6.13). CONCLUSION: The plasma NM FP rate was 16% and 3-fold higher than the same measurement in urine (4.4%). Several classes of medications had a significant impact on the rate of FP NM. Clinicians should consider use of 24-hr urine M and NM in low suspicion cases of PPGL where the diagnosis simply needs to be excluded. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.