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Objective: Pheochromocytoma/Paraganglioma (PPGL) is a rare tumor with non-specific presentations overlapping common entities like anxiety, hypertension, acute illness and episodic "spells." Assessment of urine normetanephrine or metanephrine (UNM-UMN) in real-life, where PPGL is very rare and PPGL mimics extremely common, may show overlap in results with loss of specificity depending on the reference range. We determined the extent to which UNM-UMN are high in people undergoing screening for PPGL., Design and Methods: Retrospective review of all UNM-UMN performed in a central lab serving Southern Alberta over 8 years., Results: After excluding pediatric ages and patients with CKD, there were 12,572 unique patients with 14,383 measures of UNM-UMN. 85 patients (0.7%) had markedly high UNM-UMN compatible with likely PPGL. Depending on the age category (in decades), 10-22% of all UNM results were above the upper reference limit(URL), particularly between ages of 40-60. Less than 3% had elevations in both UNM and UMN. Of those with high UNM, 99% were less than 3-fold the URL. Based on the population data, a potential new reference range for UNM is suggested, which may be more appropriate to the types of patient who undergo this form of testing., Conclusions: There is an extraordinarily high prevalence of high UNM seen in real-life use of the test. However, the vast majority of high UNM are unlikely to be PPGL given the disease rarity and the massive number of tests ordered. This suggests the current laboratory URL may be too low (poor specificity) and/or the reference range may not be appropriate to the type of patient being screened for PPGL. Depending on the frequency of use of any screening test in a population, if the disease is rare and the specificity of the test is poor, a high rate of false positive results will be expected., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Introduction: A substantial number of patients with neuroblastoma (NB) have increased excretion of catecholamines and metanephrines. Here, we have investigated the diagnostic role of plasma free metanephrines (PFM), metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) for NB, the most common extra-cranial solid tumour in children., Methods: PFM were quantified by using a commercial IVD-CE LC-MS/MS method on a TSQ Quantiva coupled to an Ultimate 3000. The method was further validated on 103 samples from pediatric subjects (54 patients with histologically confirmed NB and 49 age and sex matched controls). Correlations between PFM concentrations with clinical factors were tested. We directly compared MN, NMN, and 3MT concentrations in matched plasma and urine samples of NB patients (n = 29)., Results: 3MT and NMN showed an excellent diagnostic performance with very high specificity (100% and 95.8%, respectively) and sensitivity (88.2% and 80.4%). ROC curves were obtained (AUC of 0.93 and 0.91 for 3MT and NMN, respectively) and optimal cut-offs that could discriminate between controls and NB patients were defined. A positive correlation between NMN levels in urine and plasma (p = .0017) was found., Discussion: The determination of plasma 3MT and NMN should be taken in consideration as a new diagnostic tool for NB. Validation in prospective clinical studies in comparison to urinary catecholamines and metanephrines is warranted., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Classically, pheochromocytomas and paragangliomas result in hypertension secondary to an excess release of catecholamines. However, when the tumor arises near the renal hilum, hypertension may also be secondary to renal artery stenosis, which can occur via several purported mechanisms. We describe an unusual case of a hereditary, extra-adrenal pheochromocytoma causing right lower pole renal artery pseudostenosis, pertinent radiologic signs, relevant surgical findings, and subsequent resolution after extirpative surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Urinary catecholamines and metanephrines are biochemical indicators of pheochromocytoma. We developed and validated a rapid and precise analytical method based on solid-phase extraction (SPE) and liquid chromatography separation coupled to tandem mass spectrometry (LC-MS/MS) for measuring urinary free catecholamines and metanephrines in a clinical setting., Methods: Following SPE purification of catecholamines and metanephrines from urine specimens, chromatographic separation and quantitative detection were performed using LC-MS/MS. The developed method for simultaneous measurement of urinary free catecholamines and metanephrines was validated with clinical urine specimens and was compared with other clinical and biochemical results, including urinary total metanephrines, vanillylmandelic acid (VMA), and plasma free metanephrines., Results: The performance of our newly developed method for measuring urinary free epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), and normetanephrine (NMN), was acceptable. The recoveries and matrix effects of analytes were 61-107% and 84.5-130.7%. The linear ranges of each analyte were 3.8-2163μg/L, 7.4-2,359μg/L, 5.4-2,825μg/L, 3.5-2,466μg/L, and 3.7-2,569μg/L, and the coefficients of variation (CV) were less than 10% with respect to imprecision. Carryover and sample stability were also validated. Validation using clinical urine specimens by comparison with various biochemical results showed that urinary free metanephrines had comparable sensitivity (100%) and superior specificity (97.1%) to urinary total and plasma free metanephrines., Conclusions: The facile and reliable simultaneous measurement method for urinary free catecholamines and metanephrines using LC-MS/MS developed in this study is helpful in obtaining information about multiple metabolites and is applicable to routine clinical settings for the screening of pheochromocytoma., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: To establish reference intervals for urinary excretion of biogenic amines from birth to adulthood., Design and Methods: 865 outpatients were categorized into nine groups ranging from birthday to 25 years. Free catecholamines, total metanephrines, vanillylmandelic and homovanillic acids were determined in urine samples by HPLC with amperometric detection., Results: The ratio of each analyte-to-creatinine declined gradually from birth to 15-18 years reaching adults values. No difference was observed by sex except a lower excretion of epinephrine and metanephrine in girls than in boys below 1 year., Conclusion: Our data provide age-appropriate reference ranges for the diagnosis of tumors from neural crest in children.

Objective: The purpose of the study is to identify biochemical tests that are good predictors for the diagnosis of pheochromocytoma in patients at hypertension., Setting: Review of data from of 3826 patients studied over a 5-year period, between 1994 and 1998, at the University Hospital Virgen de la Arrixaca, Murcia, Spain., Design and Methods: A retrospective study for the diagnosis of pheochromocytoma of 24-h urinary free catecholamines (norepinephrine, epinephrine, and dopamine) measured by high-performance liquid chromatography (HPLC)-electrochemical detector (ECD), total metanephrines (MNt), and vanillylmandelic acid measured by spectrophotometric methods., Results: During this period, 57 patients were found to have pheochromocytoma, being 47 sporadic, 9 with multiple endocrine neoplasia type 2A, and 1 with neurofibromatosis. In all patients multiple endocrine neoplasia type 2A the tumor were bilateral but only in four of the sporadic tumor group (p < 0.0001, Fisher's exact test). MNt was determined to be the best discriminator of hypertension and pheochromocytoma. It scored a sensitivity of 94.7% (95% confidence interval, 88.3-99.9%), a specificity of 95.3% (89.5-99.9%), and thus had the best negative predictive value of 99.9% (99.8-99.9%), and this biochemical test also had the best positive predictive value of 23.3% (10.8-59.9%). When combining both MNt and norephinephrine, the positive predictive value to increases to 85.6% (65.3-95.6%)., Conclusion: Urinary 24-h MNt excretion level is the best single biochemical test for screening and, in combination with norephinephrine, is diagnostic of the presence of pheochromocytoma.

The possibility of the deconjugation of urinary catecholamine sulfates (CA-S) and metanephrine sulfates (MN-S) during storage was studied using a reversed-phase ion-pair HPLC method with electrochemical detection. Stability profiles of catecholamines (norepinephrine (NE), epinephrine (E) and dopamine (DA)) and metanephrines (normetanephrine (NM) and metanephrine (MN)) in preserved and unpreserved pooled urine and aqueous samples stored at 10 and 30 degrees C over 8 days were compared. Results showed that these compounds exhibited stable or declining profiles in aqueous samples but fluctuating profiles in pooled urine samples. It was concluded that deconjugation of CA-S and MN-S occurred in both preserved and unpreserved urine samples. Therefore, at 10 and 30 degrees C, levels of detected urinary catecholamines and metanephrines could be affected by both the degradation of the free amines and deconjugation of the CA-S and MN-S. Based on these findings, another batch of unpreserved urine and aqueous samples were prepared and stored at -80 degrees C. Under this condition, all compounds were found to be stable with less than 10% variations in both unpreserved urine and aqueous samples for at least 22 days. These indicated that urine samples could be stored unpreserved at -80 degrees C for at least 3 weeks without significant degradation of the free amines or deconjugation of their sulfoconjugates.

Our experiences spanning a ten-year period have been reviewed with regard to pheochromocytoma. During this period 1,890 metanephrine excretion levels were performed; 91 of these were elevated. An over-all incidence of 1.9 per cent false positive studies was found. Factors contributing to the false positive studies are discussed. Fourteen patients had 15 pheochromocytomas resected. The presenting features, diagnosis, localization, preoperative and operative management, as well as the results are presented.

A simple, but effective, procedure is described for the concurrent estimation of normetadrenaline (NMA) and metadrenaline (MA) in urine. The 3-methoxycatecholamines are adsorbed by a cation exchange resin, desorbed, separated by paper chromatography, and finally estimated spectrophotometrically after oxidation to vanillin. The mean (+/- 2 standards deviations) urinary outputs of NMA and MA from 123 normals (80 males, 43 females) in 24 hours was 2.15 +/- 1.04 and 1.79 +/- 0.96 mu mol respectively. There was no significant difference in the 24-hour urinary outputs of NMA between the male and female groups. However, the output of MA from the males was significantly higher than that from the females.

We have modified the procedure for determining total metanephrines in urine described by Gupta, Price and Keane(1) to shorten the time necessary for completion while allowing the technician time to perform other tests. The modification involves the extraction of interfering substances from urine. Instead of having to extract 3 individual tubes for each patient, we have developed an extraction that can be performed in a single tube per sample. This allows the number of tubes handled in the first portion of the procedure to be reduced by 66% and a reduction in analysis time of 25%. Day-to-day precision of the method is 8.7%. The modified procedure was compared to the original procedure by running 38 different patients by each method. The mean for the original and modified method were 1.1 mg/24h and 1.1 mg/24h respectively. The correlation coefficient was 0.9051. The t-test (p = 0.05) indicated that there was no significant difference in the means of the methods and the F-test (p = 0.05) indicated that there was no significant difference in the precision of the methods.