Biochemical diagnosis of phaeochromocytoma using plasma‐free normetanephrine, metanephrine and methoxytyramine: importance of supine sampling under fasting conditions

Abstract

High diagnostic sensitivity of plasma normetanephrine, metanephrine and methoxytyramine for the detection of PPGL can only be guaranteed using upper cut-offs of reference intervals established with blood sampling under supine fasting conditions. With such cut-offs, sampling under seated nonfasting conditions can lead to a 5·7-fold increase in false-positive results necessitating repeat sampling under supine fasting conditions.

Laboratory Evaluation of Pheochromocytoma and Paraganglioma

“…Because use of plasma metanephrines with blood sampling performed with the patient seated offers significantly inferior diagnostic accuracy compared to sampling performed with the patient supine and has no diagnostic benefit over measurements of urine fractionated metanephrines, urine testing is preferable for centers where supine sampling cannot be offered (8,33 ). This proposal agrees with recommendations by others that measurements of urine metanephrines are best for low-risk populations in which overabundance of false-positive results can be a problem for the plasma test (13 ).…”

“…As shown by Därr et al, blood sampling performed with the patient in the seated position without an overnight fast can be expected to return a close to 30% prevalence of false-positive results compared to a 5% prevalence for sampling performed on supine fasted patients (33 ). The 30 min of supine rest required to minimize the prevalence of false-positive results can, however, be a problem to implement.…”

Seasonal variations of plasma normetaneprine levels: the authors reply

“…Higher humidity and even the way people adapt to temperature may also be factors. Furthermore, we noted that the plasma concentrations of normetanephrine reported by Yu and Wei were up to 56% higher than those reported by us, presumably a consequence of seated sampling commonly adopted in the USA and which we have recently described may exaggerate responses of normetanephrine to other influences (2). We agree that regardless of the underlying mechanisms, seasonal variations should be considered in the interpretation of plasma normetanephrine levels in the diagnosis of pheochromocytoma.…”

Measurements of plasma metanephrines by immunoassay vs liquid chromatography with tandem mass spectrometry for diagnosis of pheochromocytoma

“…As described previously (15,17,18), upper cut-offs (UCs) for plasma free NMN, established under supine fasting conditions, were defined by patient age, using a curvilinear regression model (UC NMN Z0.0003792! (age 3 )C 98.9).…”

“…As has been demonstrated in a recent report (17), it should be appreciated that use of inappropriately high UCs for measurements of plasma MNs is not simply a problem confined to commercial immunoassay kits, but also a problem for laboratories where UCs have been established from reference populations sampled in the seated position rather than the recommended supine position. As indicated in that report, use of UCs established in the seated position results in a substantially decreased diagnostic sensitivity associated with a ninefold increase in FN results.…”