No abstract

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 2× upper reference limit (URL) was considered likely true PPGL. Results 1–2× URL were uncertain, requiring additional testing/follow-up despite most being false positive given the rarity of PPGL. The rate of results in the 1–2× 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 >2× 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.

P rimary aldosteronism (PA) is a common form of remediable hypertension. The aldosterone:renin ratio (ARR) is the recommended screening test for PA in individuals with hypertension with or without hypokalemia. [1][2][3] Elevations in the ratio are predominantly dependent on renin measurements, 2 thus any alteration to the renin assay will have an impact on the resulting ARR. 4 Plasma renin activity (PRA) has traditionally been used to calculate the ARR; however, measurement of direct renin concentration (DRC) has become increasingly popular because the assay procedure is less labor and time intensive. Although numerous conversion factors have been proposed in an effort to generate clinically meaningful and stable cutoffs between assays, 1 it remains uncertain whether an interchangeable relationship exists, especially as PRA and DRC are biologically distinct entities. Head-to-head comparisons are often performed by simultaneously measuring PRA and DRC, looking for correlations to establish stable conversion factors. Such studies are generally small thus limiting their general applicability. [5][6][7][8][9][10][11] Moreover, the Endocrine Society has advised that the correlation between PRA and DRC is poor at lower renin levels, the domain of greatest importance for PA screening. 1 Indeed, differences in analytical method can result in as much as a 2-fold variation in ARR cutoffs and classification error.12 On a population level, this may result in significant downstream consequences with tremendous clinical and public health implications.Addressing this, we developed a novel yet easily generalizable approach to determining ARR cutoffs using population-based data without relying on direct assay comparisons or conversion factors. The specific aim of our study was to produce a new DRC-based ARR threshold consistent with an established PRA-based ARR cutoff, thus providing diagnostic congruity with established thresholds used in routine practice. Our approach is based on 2 inter-related assumptions: first, in a defined healthcare system with a relatively static population pool, screening is performed in similar types of patients; and second, of those who are screened, the prevalence of PA has remained stable over time.Abstract-Direct renin concentration is replacing plasma renin activity in many laboratories for the investigation of primary aldosteronism, which may have a significant impact on the resulting aldosterone:renin ratios. We sought to develop a population-based approach to establishing an aldosterone:renin ratio cutoff when transitioning between assays. A population-based study was performed in Calgary, Alberta, Canada of 4301 individuals who received testing from January 2012 to November 2015. In 2014, direct renin concentration replaced plasma renin activity in routine testing. We described the prevalence of primary aldosteronism in our population before the change and, using the assumption of disease prevalence stability, determined the corresponding ratio cutoffs after the introduction of the new assay....