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Graeme Eisenhofer - One of the best experts on this subject based on the ideXlab platform.
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age specific pediatric reference intervals for plasma free Normetanephrine metanephrine 3 methoxytyramine and 3 o methyldopa particular importance for early infancy
Clinica Chimica Acta, 2019Co-Authors: Mirko Peitzsch, Anastasios Mangelis, Graeme Eisenhofer, Angela HuebnerAbstract:Abstract Background Availability of appropriately established reference intervals for biochemical tests can be troublesome in pediatrics. Here we establish age-specific continuous reference intervals for catecholamine O-methylated metabolites in children evaluated for catecholamine producing tumors, particularly younger children with suspected neuroblastoma. Methods Plasma concentrations of 3-methoxytyramine, Normetanephrine, metanephrine, and 3-O-methyldopa were analyzed by liquid chromatography tandem mass spectrometry in 533 children aged 2 days to 18 years. Results Concentrations of plasma free Normetanephrine, 3-methoxytyramine and 3-O-methyldopa were higher in neonates up until six months of age, but thereafter declined steeply to levels after one year that were Conclusion The dynamic reciprocal changes in plasma concentrations of Normetanephrine, 3-methoxytyramine and 3-O-methyldopa compared to metanephrine during early childhood suggest underlying developmental changes in extra-adrenal and adrenal chromaffin tissue that must be considered for pediatric reference intervals, particularly in infants. With such reference intervals at hand, biochemical testing for catecholamine producing tumors in young children is substantially improved.
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reference intervals for lc ms ms measurements of plasma free urinary free and urinary acid hydrolyzed deconjugated Normetanephrine metanephrine and methoxytyramine
Clinica Chimica Acta, 2019Co-Authors: Graeme Eisenhofer, Mirko Peitzsch, Anastasios Mangelis, Denise Kaden, Katharina Langton, Christina Pamporaki, Jimmy Masjkur, Aikaterini Geroula, Max Kurlbaum, Timo DeutschbeinAbstract:Abstract Background Plasma or urinary metanephrines are recommended for screening of pheochromocytomas and paragangliomas (PPGLs). Measurements of urinary free rather than deconjugated metanephrines and additional measurements of methoxytyramine represent other developments. For all measurements there is need for reference intervals. Methods Plasma free, urinary free and urinary deconjugated O-methylated catecholamine metabolites were measured by LC-MS/MS in specimens from 590 hypertensives and normotensives. Reference intervals were optimized using data from 2,056 patients tested for PPGLs. Results Multivariate analyses, correcting for age and body surface area, indicated higher plasma and urinary metanephrine in males than females and sex differences in urinary Normetanephrine and free methoxytyramine that largely reflected body size variation. There were positive associations of age with plasma metabolites, but negative relationships with urinary free metanephrine and methoxytyramine. Plasma and urinary Normetanephrine were higher in hypertensives than normotensives, but differences were small. Optimization of reference intervals using the data from patients tested for PPGLs indicated that age was the most important consideration for plasma Normetanephrine and sex most practical for urinary metabolites. Conclusion This study clarifies impacts of demographic and anthropometric variables on catecholamine metabolites, verifies use of age-specific reference intervals for plasma Normetanephrine and establishes sex-specific reference intervals for urinary metabolites.
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laboratory evaluation of pheochromocytoma and paraganglioma
Clinical Chemistry, 2014Co-Authors: Graeme Eisenhofer, Mirko PeitzschAbstract:BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are potentially lethal yet usually surgically curable causes of endocrine hypertension; therefore, once clinical suspicion is aroused it is imperative that clinicians choose the most appropriate laboratory tests to identify the tumors. CONTENT: Compelling evidence now indicates that initial screening for PPGLs should include measurements of plasma free metanephrines or urine fractionated metanephrines. LC-MS/MS offers numerous advantages over other analytical methods and is the method of choice when measurements include methoxytyramine, the O -methylated metabolite of dopamine. The plasma test offers advantages over the urine test, although it is rarely implemented correctly, rendering the urine test preferable for mainstream use. To ensure optimum diagnostic sensitivity for the plasma test, reference intervals must be established for blood samples collected after 30 min of supine rest and after an overnight fast when measurements include methoxytyramine. Similarly collected blood samples during screening, together with use of age-adjusted reference intervals, further minimize false-positive results. Extents and patterns of increases in plasma Normetanephrine, metanephrine, and methoxytyramine can additionally help predict size and adrenal vs extraadrenal locations of tumors, as well as presence of metastases and underlying germline mutations of tumor susceptibility genes. SUMMARY: Carried out correctly at specialist endocrine centers, collection of blood for measurements of plasma Normetanephrine, metanephrine, and methoxytyramine not only provides high accuracy for diagnosis of PPGLs, but can also guide clinical decision-making about follow-up imaging strategies, genetic testing, and therapeutic options. At other centers, measurements of urine fractionated metanephrines will identify most PPGLs.
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measurements of plasma methoxytyramine Normetanephrine and metanephrine as discriminators of different hereditary forms of pheochromocytoma
Clinical Chemistry, 2011Co-Authors: Graeme Eisenhofer, Jacques W.m. Lenders, Massimo Mannelli, Henri J L M Timmers, Stefan K G Grebe, Karen T Adams, Lorenz C Hofbauer, Stefan R Bornstein, Oliver Tiebel, Gennady BratslavskyAbstract:BACKGROUND: Pheochromocytomas are rare catecholamine-producing tumors derived in more than 30% of cases from mutations in 9 tumor-susceptibility genes identified to date, including von Hippel-Lindau tumor suppressor ( VHL ); succinate dehydrogenase complex, subunit B, iron sulfur (Ip) ( SDHB ); and succinate dehydrogenase complex, subunit D, integral membrane protein ( SDHD ). Testing of multiple genes is often undertaken at considerable expense before a mutation is detected. This study assessed whether measurements of plasma metanephrine, Normetanephrine, and methoxytyramine, the O-methylated metabolites of catecholamines, might help to distinguish different hereditary forms of the tumor. METHODS: Plasma concentrations of O-methylated metabolites were measured by liquid chromatography with electrochemical detection in 173 patients with pheochromocytoma, including 38 with multiple endocrine neoplasia type 2 (MEN 2), 10 with neurofibromatosis type 1 (NF1), 66 with von Hippel-Lindau (VHL) syndrome, and 59 with mutations of SDHB or SDHD . RESULTS: In contrast to patients with VHL , SDHB , and SDHD mutations, all patients with MEN 2 and NF1 presented with tumors characterized by increased plasma concentrations of metanephrine (indicating epinephrine production). VHL patients usually showed solitary increases in Normetanephrine (indicating norepinephrine production), whereas additional or solitary increases in methoxytyramine (indicating dopamine production) characterized 70% of patients with SDHB and SDHD mutations. Patients with NF1 and MEN 2 could be discriminated from those with VHL , SDHB , and SDHD gene mutations in 99% of cases by the combination of Normetanephrine and metanephrine. Measurements of plasma methoxytyramine discriminated patients with SDHB and SDHD mutations from those with VHL mutations in an additional 78% of cases. CONCLUSIONS: The distinct patterns of plasma catecholamine O-methylated metabolites in patients with hereditary pheochromocytoma provide an easily used tool to guide cost-effective genotyping of underlying disease-causing mutations.
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Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines.
Clinical chemistry, 2005Co-Authors: Graeme Eisenhofer, Jacques W.m. Lenders, David S. Goldstein, Massimo Mannelli, Gyorgy Csako, Frederieke M. Brouwers, Karel PacakAbstract:Background: Measurements of plasma free metanephrines (Normetanephrine and metanephrine) provide a useful test for diagnosis of pheochromocytoma and may provide other information about the nature of these tumors. Methods: We examined relationships of tumor size, location, and catecholamine content with plasma and urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We then prospectively examined whether measurements of plasma free metanephrines could predict tumor size and location in an additional 16 patients. Results: Relative proportions of epinephrine and norepinephrine in tumor tissue were closely matched by relative increases of plasma or urinary metanephrine and Normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed strong positive relationships with summed plasma concentrations or urinary outputs of metanephrine and Normetanephrine ( r = 0.81 and 0.77; P 15% of the combined increases of Normetanephrine and metanephrine either had adrenal locations or appeared to be recurrences of previously resected adrenal tumors. Measurements of plasma free metanephrines predicted tumor diameter to within a mean of 30% of actual diameter, and high plasma concentrations of free metanephrine relative to Normetanephrine accurately predicted adrenal locations. Conclusions: Measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures.
Claudia E Reusch - One of the best experts on this subject based on the ideXlab platform.
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effects of trilostane on urinary catecholamines and their metabolites in dogs with hypercortisolism
BMC Veterinary Research, 2017Co-Authors: Nadja S Sieberruckstuhl, Elena Salesov, S. Quante, Barbara Riond, Katharina Rentsch, Claudia E Reusch, Regina Hofmannlehmann, Felicitas S. BorettiAbstract:Glucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and Normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy. Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and Normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. Untreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and Normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and Normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy. Influences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and Normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and Normetanephrine:creatinine ratios during trilostane therapy.
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urinary and plasma catecholamines and metanephrines in dogs with pheochromocytoma hypercortisolism nonadrenal disease and in healthy dogs
Journal of Veterinary Internal Medicine, 2015Co-Authors: Elena Salesov, Felicitas S. Boretti, Barbara Riond, Katharina Rentsch, Nadja S Sieberruckstuhl, Regina Hofmannlehmann, Patrick R Kircher, E Grouzmann, Claudia E ReuschAbstract:BACKGROUND: Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine. OBJECTIVES: To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC. ANIMALS Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs. METHODS Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at -80°C before analysis using high-pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration. RESULTS: Dogs with PC had significantly higher urinary Normetanephrine and metanephrine : creatinine ratios and significantly higher plasma-total and free Normetanephrine and plasma-free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary Normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma Normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma. CONCLUSION AND CLINICAL IMPORTANCE: Measurement of Normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.
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urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma and in healthy dogs
Journal of Veterinary Internal Medicine, 2010Co-Authors: S. Quante, Peter H Kook, C Mueller, S Schellenberg, Eric Zini, Nadja S Sieberruckstuhl, Claudia E ReuschAbstract:Background: Urinary catecholamines and metanephrines are used for the diagnosis of pheochromocytoma (PHEO) in dogs. Hyperadrenocorticism (HAC) is an important differential diagnosis for PHEO. Objectives: To measure urinary catecholamines and metanephrines in dogs with HAC. Animals: Fourteen dogs with HAC, 7 dogs with PHEO, and 10 healthy dogs. Methods: Prospective clinical trial. Urine was collected during initial work-up in the hospital; in dogs with HAC an additional sample was taken at home 1 week after discharge. Parameters were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration. Results: Dogs with HAC had significantly higher urinary epinephrine, norepinephrine and Normetanephrine to creatinine ratios than healthy dogs. Urinary epinephrine, norepinephrine, and metanephrine to creatinine ratios did not differ between dogs with HAC and dogs with PHEO, whereas the urinary Normetanephrine to creatinine ratio was significantly higher (P= .011) in dogs with PHEO (414, 157.0–925.0, median, range versus (117.5, 53.0–323.0). Using a cut-off ratio of 4 times the highest Normetanephrine to creatinine ratio measured in controls, there was no overlap between dogs with HAC and dogs with PHEO. The variables determined in urine samples collected at home did not differ from those collected in the hospital. Conclusion and Clinical Importance: Dogs with HAC might have increased concentrations of urinary catecholamines and Normetanephrine. A high concentration of urinary Normetanephrine (4 times normal), is highly suggestive of PHEO.
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urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma
Journal of Veterinary Internal Medicine, 2007Co-Authors: Peter H Kook, Martin Hersberger, T M Glaus, Claudia E ReuschAbstract:Background:Measurement of high concentrations of urine catecholamines and metanephrines is useful in diagnosing pheochromocytoma in humans. Stress increases Catecholamine excretion in urine. Hypothesis:Stress of a hospital visit increases urinary Catecholamine and metanephrine excretion in dogs. Animals:Fourteen clinically normal dogs, 2 dogs with pheochromocytoma Methods:Voided urine samples were collected by the owners 7 days before (t — 7), during the hospital visit immediately after diagnostic procedures (t0), as well as 1 (t1) and 7 days (t7) after the hospital visit. Urine Catecholamine and metanephrine concentrations were measured using high-pressure liquid chromatography and expressed as ratios to urine creatinine concentration. Results:In client-owned dogs epinephrine and norepinephrine ratios at t0 were significantly higher compared with ratios at t7. Metanephrine and Normetanephrine ratios at t — 7, t0, and t1 did not differ significantly from each other; however, at t7 they were significantly lower compared to values at t — 7. In staff-owned dogs no significant differences were detected among the different collecting time points for any variable. Metanephrine and Normetanephrine ratios were significantly higher in client-owned dogs compared to staff-owned dogs at t — 7, t0, and t1 but not at t7. Conclusions and Clinical Importance: Stress associated with a hospital visit and with the sampling procedure causes increases in urine Catecholamine and metanephrine excretion. Urine collection for the diagnosis of pheochromocytoma probably should take place at home after adaptation to the sampling procedure.
Mirko Peitzsch - One of the best experts on this subject based on the ideXlab platform.
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biochemical testing for neuroblastoma using plasma free 3 o methyldopa 3 methoxytyramine and Normetanephrine
Pediatric Blood & Cancer, 2020Co-Authors: Mirko Peitzsch, Elizabeth R Butch, Elizabeth Lovorn, Anastasios Mangelis, Wayne L Furman, Victor M Santana, Barbara Hero, Frank Berthold, Barry L Shulkin, Angela HuebnerAbstract:BACKGROUND Neuroblastoma, the most common extracranial solid tumor of childhood, produces catecholamines that are metabolized within tumor cells. Homovanillic acid (HVA) and vanillylmandelic acid (VMA), the end products of catecholamine metabolism, have limited accuracy for testing of the tumors. This study assessed whether metabolites produced in earlier steps of catecholamine metabolism might offer improved diagnostic accuracy over urinary HVA and VMA. PROCEDURE Plasma concentrations of 3-methoxytyramine, Normetanephrine, and metanephrine were measured in two pediatric cohorts: (i) 96 children with confirmed neuroblastoma and (ii) 41 children with signs and symptoms of a catecholamine-producing tumor or other neoplasms and in whom neuroblastoma was excluded. Additional measurements of plasma 3-O-methyldopa and relationships of metabolites to MYCN amplification were examined in patient subgroups. RESULTS Overall, 94 of the 96 patients with neuroblastoma had concentrations of 3-methoxytyramine or Normetanephrine above age-specific upper limits of reference intervals, providing a diagnostic sensitivity of 97.9% that was higher (P < 0.0001) than that of 82.2% for HVA and VMA. One of the two patients with normal plasma results showed an elevation of plasma 3-O-methyldopa. Diagnostic specificities were, respectively, 95.1% and 84.8%. Areas under receiver-operating characteristic curves confirmed the superior diagnostic power of the plasma than the urinary test (0.994 vs 0.945; P = 0.0095). Ratios of plasma 3-methoxytyramine to Normetanephrine were 7.2-fold higher (P < 0.0001) for patients who had neuroblastomas with MYCN amplification than without MYCN amplification. CONCLUSIONS Measurements of plasma 3-methoxytyramine and Normetanephrine provide a highly accurate diagnostic test for neuroblastoma and also offer potential for prognostic risk stratification.
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age specific pediatric reference intervals for plasma free Normetanephrine metanephrine 3 methoxytyramine and 3 o methyldopa particular importance for early infancy
Clinica Chimica Acta, 2019Co-Authors: Mirko Peitzsch, Anastasios Mangelis, Graeme Eisenhofer, Angela HuebnerAbstract:Abstract Background Availability of appropriately established reference intervals for biochemical tests can be troublesome in pediatrics. Here we establish age-specific continuous reference intervals for catecholamine O-methylated metabolites in children evaluated for catecholamine producing tumors, particularly younger children with suspected neuroblastoma. Methods Plasma concentrations of 3-methoxytyramine, Normetanephrine, metanephrine, and 3-O-methyldopa were analyzed by liquid chromatography tandem mass spectrometry in 533 children aged 2 days to 18 years. Results Concentrations of plasma free Normetanephrine, 3-methoxytyramine and 3-O-methyldopa were higher in neonates up until six months of age, but thereafter declined steeply to levels after one year that were Conclusion The dynamic reciprocal changes in plasma concentrations of Normetanephrine, 3-methoxytyramine and 3-O-methyldopa compared to metanephrine during early childhood suggest underlying developmental changes in extra-adrenal and adrenal chromaffin tissue that must be considered for pediatric reference intervals, particularly in infants. With such reference intervals at hand, biochemical testing for catecholamine producing tumors in young children is substantially improved.
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reference intervals for lc ms ms measurements of plasma free urinary free and urinary acid hydrolyzed deconjugated Normetanephrine metanephrine and methoxytyramine
Clinica Chimica Acta, 2019Co-Authors: Graeme Eisenhofer, Mirko Peitzsch, Anastasios Mangelis, Denise Kaden, Katharina Langton, Christina Pamporaki, Jimmy Masjkur, Aikaterini Geroula, Max Kurlbaum, Timo DeutschbeinAbstract:Abstract Background Plasma or urinary metanephrines are recommended for screening of pheochromocytomas and paragangliomas (PPGLs). Measurements of urinary free rather than deconjugated metanephrines and additional measurements of methoxytyramine represent other developments. For all measurements there is need for reference intervals. Methods Plasma free, urinary free and urinary deconjugated O-methylated catecholamine metabolites were measured by LC-MS/MS in specimens from 590 hypertensives and normotensives. Reference intervals were optimized using data from 2,056 patients tested for PPGLs. Results Multivariate analyses, correcting for age and body surface area, indicated higher plasma and urinary metanephrine in males than females and sex differences in urinary Normetanephrine and free methoxytyramine that largely reflected body size variation. There were positive associations of age with plasma metabolites, but negative relationships with urinary free metanephrine and methoxytyramine. Plasma and urinary Normetanephrine were higher in hypertensives than normotensives, but differences were small. Optimization of reference intervals using the data from patients tested for PPGLs indicated that age was the most important consideration for plasma Normetanephrine and sex most practical for urinary metabolites. Conclusion This study clarifies impacts of demographic and anthropometric variables on catecholamine metabolites, verifies use of age-specific reference intervals for plasma Normetanephrine and establishes sex-specific reference intervals for urinary metabolites.
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laboratory evaluation of pheochromocytoma and paraganglioma
Clinical Chemistry, 2014Co-Authors: Graeme Eisenhofer, Mirko PeitzschAbstract:BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are potentially lethal yet usually surgically curable causes of endocrine hypertension; therefore, once clinical suspicion is aroused it is imperative that clinicians choose the most appropriate laboratory tests to identify the tumors. CONTENT: Compelling evidence now indicates that initial screening for PPGLs should include measurements of plasma free metanephrines or urine fractionated metanephrines. LC-MS/MS offers numerous advantages over other analytical methods and is the method of choice when measurements include methoxytyramine, the O -methylated metabolite of dopamine. The plasma test offers advantages over the urine test, although it is rarely implemented correctly, rendering the urine test preferable for mainstream use. To ensure optimum diagnostic sensitivity for the plasma test, reference intervals must be established for blood samples collected after 30 min of supine rest and after an overnight fast when measurements include methoxytyramine. Similarly collected blood samples during screening, together with use of age-adjusted reference intervals, further minimize false-positive results. Extents and patterns of increases in plasma Normetanephrine, metanephrine, and methoxytyramine can additionally help predict size and adrenal vs extraadrenal locations of tumors, as well as presence of metastases and underlying germline mutations of tumor susceptibility genes. SUMMARY: Carried out correctly at specialist endocrine centers, collection of blood for measurements of plasma Normetanephrine, metanephrine, and methoxytyramine not only provides high accuracy for diagnosis of PPGLs, but can also guide clinical decision-making about follow-up imaging strategies, genetic testing, and therapeutic options. At other centers, measurements of urine fractionated metanephrines will identify most PPGLs.
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biochemical diagnosis of phaeochromocytoma using plasma free Normetanephrine metanephrine and methoxytyramine importance of supine sampling under fasting conditions
Clinical Endocrinology, 2014Co-Authors: Roland Därr, Mirko Peitzsch, Christina Pamporaki, Konstanze Miehle, Aleksander Prejbisz, Mariola Peczkowska, Dirk Weismann, Felix Beuschlein, Richard O Sinnott, Stefan R BornsteinAbstract:SummaryObjective To document the influences of blood sampling under supine fasting versus seated nonfasting conditions on diagnosis of phaeochromocytomas and paragangliomas (PPGL) using plasma concentrations of Normetanephrine, metanephrine and methoxytyramine. Design and methods Biochemical testing for PPGL was performed on 762 patients at six centres, two of which complied with requirements for supine sampling after an overnight fast and four of which did not. Phaeochromocytomas and paragangliomas were found in 129 patients (67 noncompliant, 62 compliant) and not in 633 patients (195 noncompliant, 438 compliant). Results Plasma concentrations of Normetanephrine and methoxytyramine did not differ between compliant and noncompliant sampling conditions in patients with PPGL but were 49-51% higher in patients without PPGL sampled under noncompliant compared with compliant conditions. The 97·5 percentiles of distributions were also higher under noncompliant compared with compliant conditions for Normetanephrine (1·29 vs 0·79 nmol/l), metanephrine (0·49 vs 0·41 nmol/l) and methoxytyramine (0·42 vs 0·18 nmol/l). Use of upper cut-offs established from seated nonfasting sampling conditions resulted in substantially decreased diagnostic sensitivity (98% vs 85%). In contrast, use of upper cut-offs established from supine fasting conditions resulted in decreased diagnostic specificity for testing under noncompliant compared with compliant conditions (71% vs 95%). Conclusions 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.
Kerttu Irjala - One of the best experts on this subject based on the ideXlab platform.
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reference intervals for 24 h urinary Normetanephrine metanephrine and 3 methoxy 4 hydroxymandelic acid in hypertensive patients
Clinical Chemistry, 1992Co-Authors: Veli Kairisto, P K Koskinen, Kari Mattila, J Puikkonen, Arja Virtanen, I Kantola, Kerttu IrjalaAbstract:The urinary excretion of Normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid was quantified by HPLC in hypertensive patients who were being routinely investigated for the exclusion of pheochromocytoma. The data were used to calculate reference intervals for these analytes. Age- and sex-specific 95% reference intervals for 24-h urinary excretion were as follows (mumol/24 h): Normetanephrine in men ages 16-35 years (n = 17) 0.7-3.4, in men older than 35 years (n = 121) 0.8-5.1, in women ages 16-35 years (n = 41) 0.5-2.1, and in women older than 35 years (n = 144) 0.6-3.3 mumol/24 h; metanephrine in men (n = 138) 0.3-2.0, and in women (n = 185) 0.2-1.3; and 3-methoxy-4-hydroxymandelic acid in men (n = 142) 10-54, and in women (n = 184) 9-38. Normetanephrine or metanephrine excretion rates or both exceeded the proposed reference intervals in seven of the eight patients with pheochromocytoma. Determination of 3-methoxy-4-hydroxymandelic acid excretion did not yield any additional diagnostic information.
Veli Kairisto - One of the best experts on this subject based on the ideXlab platform.
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reference intervals for 24 h urinary Normetanephrine metanephrine and 3 methoxy 4 hydroxymandelic acid in hypertensive patients
Clinical Chemistry, 1992Co-Authors: Veli Kairisto, P K Koskinen, Kari Mattila, J Puikkonen, Arja Virtanen, I Kantola, Kerttu IrjalaAbstract:The urinary excretion of Normetanephrine, metanephrine, and 3-methoxy-4-hydroxymandelic acid was quantified by HPLC in hypertensive patients who were being routinely investigated for the exclusion of pheochromocytoma. The data were used to calculate reference intervals for these analytes. Age- and sex-specific 95% reference intervals for 24-h urinary excretion were as follows (mumol/24 h): Normetanephrine in men ages 16-35 years (n = 17) 0.7-3.4, in men older than 35 years (n = 121) 0.8-5.1, in women ages 16-35 years (n = 41) 0.5-2.1, and in women older than 35 years (n = 144) 0.6-3.3 mumol/24 h; metanephrine in men (n = 138) 0.3-2.0, and in women (n = 185) 0.2-1.3; and 3-methoxy-4-hydroxymandelic acid in men (n = 142) 10-54, and in women (n = 184) 9-38. Normetanephrine or metanephrine excretion rates or both exceeded the proposed reference intervals in seven of the eight patients with pheochromocytoma. Determination of 3-methoxy-4-hydroxymandelic acid excretion did not yield any additional diagnostic information.