Random ‘spot’ urinary metanephrines compared with 24-h-urinary and plasma results in phaeochromocytomas and paragangliomas

Abstract

<jats:sec> <jats:title>Background</jats:title> <jats:p>In patients with phaeochromocytomas or paragangliomas (PPGLs), 24-h urine collections for metanephrines (uMNs) are cumbersome.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To evaluate the diagnostic utility of ratios to creatinine of ‘spot’ uMNs.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Concentrations of uMNs and plasma metanephrines (pMNs) were measured by HPLC-mass-spectrometry. We retrospectively compared correlations of 24-h-urine output and ratio to creatinine in historical specimens and prospectively assessed 24-h and contemporaneous spot urines and, where possible, pMNs. Using trimmed log-transformed values, we derived reference intervals based on age and sex for spot urines. We used multiples of upper limit of normal (ULNs) to compare areas under curves (AUCs) for receiver-operator characteristic curves of individual, and sum and product of, components.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In 3143 24-h-urine specimens on 2416 patients, the correlation coefficients between the ratios and outputs of metanephrine, normetanephrine and 3-methoxytyramine in 24-h urines were 0.983, 0.905 and 0.875, respectively. In 96 patients, the correlations between plasma concentrations, urine output and ratios in spot specimens were similar to those for raw output or ratios in 24-h specimens. Of the 160 patients with PPGLs, the CIs for AUCs for individual metabolites overlapped for all four types of measurement, as did those for the sum of the multiple ULNs although these were slightly higher (AUC for spot urine: 0.838 (0.529–1), plasma: 0.929 (0.874–0.984) and output: 0.858 (0.764–0.952)).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Ratios of fractionated metanephrines to creatinine in spot urine samples appear to have a similar diagnostic power to other measurements. The ease of spot urine collection may facilitate diagnosis and follow-up of PPGLs through improved patient compliance.</jats:p> </jats:sec>

A UK national audit of the laboratory investigation of phaeochromocytoma and paraganglioma

“…The survey also found that 10 laboratories accept either overnight or random urine samples for UMET, at least in certain circumstances. The Endocrine Society Guideline states that a 24-h urine collection is preferred, although there is a some evidence that overnight or random UMET may perform well as a diagnostic test compared to 24-h collection [41][42][43] While all centres using PMET requested EDTA plasma, the acceptance criteria were quite variable with the maximum permissible delay between sample collection and centrifugation varying between 15 min and 6 h. Having a defined policy in place for the acceptance of PMET samples is important as published data show that while PMET may be stable pre-centrifugation for up to 3 h when kept at 4°C, 44 concentrations change quite rapidly at room temperature with concentrations potentially initially increasing (due to residual activity of the enzyme catechol-O-methyltransferase) and then undergoing degradation. 44,45 Post-centrifugation, metanephrines are not stable at room temperature with significant degradation observed within 24 h. Plasma kept at 4°C appears to be stable for up to 3 days without significant degradation and frozen plasma is stable for at least 1 month.…”

Microneedle-based nanoporous gold electrochemical sensor for real-time catecholamine detection

“…The electrochemical characterization of the microneedle electrode before and after h-nPG electrodeposition has already been investigated by CV in a solution of Fe(CN) 6 3− / 4− , as reported in our previous work [36]. It is interesting to note that the enhancement of both anodic and cathodic peak current densities after the h-nPG electrodeposition was much larger than that registered with planar gold electrodes after the same modification.…”

“…EIS experiments were carried out at equilibrium potential called open-circuit potential (OCP) without potential of the redox probe (0.22 V vs Ag/AgCl), bias voltage in the frequency range of 0.1-10 3 Hz using an AC signal of 10-mV amplitude at a formal potential of the redox probe (0.22 V vs Ag/AgCl), using Autolab Potentiostat/Galvanostat (Eco Chemie, Netherlands). EIS measurements were performed using 10 mL of PBS solution containing mixture of 5 mM Fe(CN) 6 3− /Fe(CN) 6 4− , as electrochemical probe.…”

“…Considering that CAs have a very short half-live and are often secreted in an episodic manner, their levels might appear normal between secretory phases [6], creating a diagnostic problem. The opportunity for new methods, continuous monitoring, and real-time detection of CAs could overcome such issues, and offer a dramatic improvement in the diagnosis and follow-up management of diseases characterized by CA excess such as phaeochromocytomas and paragangliomas.…”

What is the rationale for the laboratory workup for suspected pheochromocytomas and paragangliomas?

“…Emerging studies have noted that the sensitivity and specifi city of spot urine samples correlate well with those of 24-hour samples, but at present the evidence is insuffi cient to recommend adopting this strategy in routine clinical practice. 2,11 Vanillylmandelic acid has poor sensitivity and is not indicated in the initial biochemical workup for possible PPGLs. 12…”