A high rate of modestly elevated plasma normetanephrine in a population referred for suspected PPGL when measured in a seated position

Objective: Determine rate of high plasma normetanephrine or metanephrine (PNM-PMN) in a large sample of patients according to PNM-PMN posture and age-adjusted references. Design: Retrospective re-analysis of PNM-PMN from a Canadian reference laboratory (n = 5452), 2011-2015; most were in seated position (n = 5112) rather than supine (n = 340). An international PPGL database demonstrated expected distribution of supine PNM-PMN in PPGL patients. Methods: All PNM-PMN from a tertiary referral laboratory were reviewed. Any PNM-PMN result greater than 2x upper reference limit (URL) was considered likely true PPGL. Results 1-2x URL were uncertain, requiring additional testing/follow-up despite most being false positive given the rarity of PPGL. The rate of results in the 1-2x URL category were calculated for each group according to collection posture and differing published URL: seated, supine or supine age adjusted. Results: When collected and interpreted by seated URL, 19.6% of PNM required additional testing; only 4.6% being >2x URL. For patients over age 50 years, the abnormal rate was 24.9%. When collected supine, interpreted by supine age-adjusted URL, only 5.3% of PNM were mildly elevated. Possible false positives may be even lower when considering PMN or plasma methoxytyramine which were commonly high in true PPGL despite mild PNM elevations. Conclusions: In a general medical population, seated PNM has a high rate of abnormal results, far exceeding expected prevalence. Supine measurement with supine, age-adjusted interpretation is strongly preferred prior to costly or invasive PPGL investigations. Summary: Review of 5452 plasma normetanephrine measurements showed 20% to be high, likely false positives for most. Supine, age-adjusted measures were half as likely to be elevated.