Dietary Influences on Plasma and Urinary Metanephrines: Implications for Diagnosis of Catecholamine-Producing Tumors

Context: A substantial number of patients with head and neck paragangliomas (HNPGLs) have biochemically active tumors, evidenced by increased urinary excretion of catecholamines and metabolites, including 3-methoxytyramine (3MT). It is unclear whether plasma levels of these parameters are more sensitive to detect biochemical activity in HNPGL patients than urinary excretion rates. Objective: To compare plasma free levels vs urinary excretion rates of deconjugated 3MT and combined metanephrines (MNs) in patients with HNPGL. Patients and methods: We included 124 consecutive patients with HNPGL for screening of catecholamine excess by measurement of 24-h urinary excretion rates of deconjugated (nor)metanephrine, (nor)epinephrine, dopamine, vanillylmandelic acid, 3MT, and plasma free levels of (nor)metanephrine and 3MT. Results: Plasma free 3MT levels were increased in 35 of the 124 patients (28%), whereas 24-h urinary excretion of deconjugated 3MT was increased in 30 patients (24%) (PZ0.13). Plasma free MN levels were increased in seven patients (6%) and urinary deconjugated MN levels in six patients (5%) (PZ1.00). Plasma free normetanephrine (NMN) levels were increased in seven patients (6%), and five patients had increased urinary excretion of deconjugated NMN (4%) (PZ0.69). Plasma free combined MN levels (NMN, MN, and 3MT) were increased in 41 patients (33%), whereas 24-h urinary excretion rates of deconjugated combined MNs were increased in 33 patients (27%, P!0.05). Conclusions: The combined levels of free MNs and free 3MT in plasma indicate a higher number of biochemically active HNPGLs than the 24-h urinary excretion rates of these markers.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Plasma levels of free metanephrines and 3-methoxytyramine indicate a higher number of biochemically active HNPGL than 24-h urinary excretion rates of catecholamines and metabolites

Duinen

Corssmit

Jong

et al. 2013

“…The sulfotransferase SULT1A3 is very active in the gastrointestinal tract, and may produce conjugated metanephrines after consumption of foods (31). Dietary influences have been reported not to influence plasma total metanephrines (32), whereas a recent publication has established that a standardized meal rich in metanephrines (including six bananas) may induce an increase of plasma-deconjugated normetanephrine, plasma-deconjugated and free methoxytyramine, and urine-deconjugated normetanephrine (33).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of free and total metanephrines in plasma and fractionated metanephrines in urine of patients with pheochromocytoma

Grouzmann

Drouard-Troalen

Baudin

et al. 2010

Background: Plasma free and urinary metanephrines are recognized biomarkers for the assessment of pheochromocytoma. Plasma total metanephrines with a long half-life may represent another useful biomarker. Objective: The aim of this study is to evaluate the diagnostic performances of plasma total metanephrines alone or combined with free metanephrines and fractionated 24-h urinary metanephrines. Methods: A retrospective, case-control diagnostic test study was conducted between 1999 and 2007 in two university hospitals in Switzerland and two institutions in France. The patients included 46 cases with histologically proven pheochromocytoma, and 181 controls suspected of tumor with negative investigations and 3-year follow-up. None had renal dysfunction. Sensitivity and specificity were compared after expressing each measurement result as a ratio over its upper reference limit, adding the ratios of normetanephrine and metanephrine, and defining cut-off values of 1 or 2 for this sum. Results: Applying a cut-off value of 1, plasma free and total metanephrines and urinary fractionated metanephrines had similar sensitivities of 96% (95% confidence interval, 86-99%), 95% (85-99%), and 95% (84-99%) along with similar specificities of 89% (83-94%), 91% (84-95%), and 86% (80-91%). A cut-off of 2 for the sum of ratios over reference limit improves the specificity, and it can be used for a confirmation test based on another biomarker taken among the three biomarkers. Conclusion: All three metanephrine-based tests perform equivalently for diagnosing pheochromocytoma in the absence of renal insufficiency, and can be conveniently associated two by two for confirming/excluding tumor.

“…As other assays, such as renin and aldosterone, are likely to be performed at some point when investigating hypertension or adrenal tumours, it may be easy to obtain a rested supine posture for all patients. An interesting point is that diet does not affect free pNMA and pMA (25), which is particularly suitable for outpatients.…”

Section: Clinical Considerationsmentioning

confidence: 99%

Phasing-in plasma metanephrines determination

Brossaud¹,

Gosse²,

Gatta³

et al. 2013

Objectives: We set up plasma normetanephrine (pNMA) and metanephrine (pMA) assays as they demonstrated their usefulness for diagnosing phaeochromocytomas. Our scope is to describe some practical laboratory aspects and the clinical relevance of these assays in our endocrinological or cardiological departments. Methods: We retrospectively reviewed the results of MA from a population of in-and outpatients over a 7-year period. Subjects (nZ2536) from endocrinological or cardiological departments were investigated (66 phaeochromocytomas). Urinary NMA (uNMA) and pNMA, and urinary MA (uMA) and pMA were assayed by HPLC with electrochemical detection. Results: pNMA and pMA assays are now more frequently requested than uNMA and uMA. This changed our laboratory work load with improved delivery, sensitivity and reliability of plasma assays as well as reduced apparatus maintenance time. The pNMA and pMA upper reference limits (URLs) of subjects with no phaeochromocytoma were 1040 and 430 pmol/l respectively. Sensitivity and specificity based on receiver operating characteristic curves optimal points were 83 and 93% for pNMA at 972 pmol/l and 67 and 98% for pMA at 638 pmol/l. Sensitivity and specificity of paired tests of pMA (positive test: at least one analyte above its URLs) were 100 and 91% respectively. Conclusion: The very low concentration of analytes requires a sustained very good apparatus analytical sensitivity. This can be obtained in an up-to-date laboratory. In terms of clinical performances, assays in plasma or urine are equivalent. Depending on local preferences, populations, strategies or departments, requests for one or the other assay may sustain the need for specifically defined reference ranges.