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Biomedical Chromatography : BMC Sep 2006The enzyme catechol-O-methyltransferase (COMT) plays an important role in the metabolism of catechol estrogens and degradation of the catecholamine neurotransmitters,...
The enzyme catechol-O-methyltransferase (COMT) plays an important role in the metabolism of catechol estrogens and degradation of the catecholamine neurotransmitters, such as epinephrine. Several analytical methods, mainly high-performance liquid chromatography with electrochemical amperometric detection, have been reported for the analysis of catecholamines and their metabolites in biological fluids. In this paper we report the relevance of controlling temperature in calibration procedures of metanephrine, an O-methylated product of catechol-O-methyltransferase, using epinephrine as substrate. The results at higher temperatures show shorter retention times of metanephrine, no undue band-broadening and increased electro signals. This study also showed that, despite different temperatures leading to similarly specific activities of recombinant human COMT as expected, there are additional advantages in flow analytical methods where good sensitivity, efficiency and selectivity is required, mainly in tissues with low levels of COMT activity.
Topics: Catechol O-Methyltransferase; Chromatography, High Pressure Liquid; Electrochemistry; Metanephrine; Recombinant Proteins; Reproducibility of Results; Sensitivity and Specificity; Temperature
PubMed: 16470514
DOI: 10.1002/bmc.623 -
Clinical Chemistry Nov 2022
Topics: Humans; Metanephrine; Pheochromocytoma; Adrenal Gland Neoplasms
PubMed: 37051684
DOI: 10.1093/clinchem/hvac060 -
Clinical Chemistry Oct 1986Sensitive and specific radioimmunoassays of metanephrine and normetanephrine were developed by use of 125I-labeled synephrine and specific metanephrine antibody, and... (Comparative Study)
Comparative Study
Sensitive and specific radioimmunoassays of metanephrine and normetanephrine were developed by use of 125I-labeled synephrine and specific metanephrine antibody, and 125I-labeled octopamine and specific normetanephrine antibody. Specific antibody for both metanephrine and normetanephrine was raised in rabbits by immunization with bovine serum albumin conjugated with the corresponding hapten, prepared by the method of Grota and Brown (Endocrinology 1976;98:615). The detection limits of the metanephrine and the normetanephrine radioimmunoassays were 2 and 6 pg/tube, respectively. Mean plasma metanephrine and normetanephrine values for 24 normal subjects were 62 (SD 14) and 100 (SD 40) ng/L, respectively. Mean urinary metanephrine and normetanephrine values for 22 normal subjects were 154 (SD 74) and 217 (SD 109) micrograms/day. For 14 pheochromocytoma patients, plasma metanephrine and normetanephrine values ranged from 29 to 683 and from 28 to 7850 ng/L, and urinary metanephrine and normetanephrine values were 606 to 6630 and 296 to 4800 micrograms/day, respectively. The present methods are simple and suitable for routine tests or for mass screening for pheochromocytoma.
Topics: Adrenal Gland Neoplasms; Antibody Specificity; Epinephrine; Humans; Immune Sera; Iodine Radioisotopes; Metanephrine; Normetanephrine; Octopamine; Pheochromocytoma; Radioimmunoassay; Reference Values; Synephrine
PubMed: 3093120
DOI: No ID Found -
Journal of Veterinary Internal Medicine Jan 2023Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs).
BACKGROUND
Measurement of free metanephrines is recommended for screening of pheochromocytoma (PCC) but requires appropriate reference intervals (RIs).
HYPOTHESIS/OBJECTIVES
To report RIs for plasma, urinary and salivary concentrations of free metanephrines and to determine the diagnostic performance of plasma free normetanephrine (pNMN) and metanephrine (pMN) concentrations in dogs with PCC, hypercortisolism (HC), and nonadrenal illness (NAI).
ANIMALS
Eighty healthy dogs, 11 PCC dogs, 25 HC dogs, 6 NAI dogs.
METHODS
Plasma, urine, and saliva were collected prospectively from healthy dogs, and free metanephrine concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, medical records of dogs that had plasma free metanephrine concentrations measured by LC-MS/MS between 2018-2021 were studied retrospectively.
RESULTS
The RIs for free metanephrines in plasma, urine and saliva are reported. Dogs with PCC had significantly higher pNMN than dogs with HC (P < .001) and NAI (P = .002). The PCC dogs had significantly higher pMN than HC dogs (P < .001), but not higher than NAI dogs (P = .29). Using the upper reference limit, pNMN (>3.56 nmol/L) showed high sensitivity (100%, 95% confidence interval [CI]: 72-100) and specificity (94%, 95% CI: 79-99) for diagnosis of PCC, whereas pMN (>2.49 nmol/L) showed moderate sensitivity (73%, 95% CI: 39-94) and high specificity (94%, 95% CI: 79-99).
CONCLUSIONS AND CLINICAL IMPORTANCE
With establishment of these RIs, biochemical testing for PCC in dogs can be substantially improved. Measurement of pNMN is superior to pMN in dogs with PCC.
Topics: Dogs; Animals; Metanephrine; Pheochromocytoma; Chromatography, Liquid; Retrospective Studies; Tandem Mass Spectrometry; Normetanephrine; Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Dog Diseases
PubMed: 36637037
DOI: 10.1111/jvim.16624 -
Journal of Veterinary Internal Medicine 2010Urinary catecholamines and metanephrines are used for the diagnosis of pheochromocytoma (PHEO) in dogs. Hyperadrenocorticism (HAC) is an important differential diagnosis...
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.
Topics: Adrenal Gland Neoplasms; Adrenocortical Hyperfunction; Animals; Catecholamines; Creatinine; Dog Diseases; Dogs; Female; Male; Metanephrine; Pheochromocytoma
PubMed: 20707840
DOI: 10.1111/j.1939-1676.2010.0578.x -
Endocrine Regulations Jan 2023Pheochromocytomas (PHEO) and paraganglioma (PGLs) are rare neuroendocrine catecholamine-producing tumors that arise from the chromaffin cells of either the adrenal...
Pheochromocytomas (PHEO) and paraganglioma (PGLs) are rare neuroendocrine catecholamine-producing tumors that arise from the chromaffin cells of either the adrenal medulla or extra-adrenal paraganglionic tissues. Despite the recent advances in imaging technologies, biochemical evidence of excessive catecholamine production by the tumor is considered the most important test for the diagnosis of these tumors. The aim of the present study is to investigate the role of the catecholamine metabolites (normetanephrine and metanephrine) levels in the diagnosis of PHEO/PGLs and to evaluate if their levels correlate with the size of these tumors. Twenty-five patients were included in the study during the time period of 10 years. Their data were compared with another set of 25 patients to obtain the sensitivity and specificity of metanephrine and normetanephrine in the diagnosis of PHEO/PGLs. The tumor size was reviewed in every patient to obtain the correlation coefficient between the tumor sizes and the plasma/24-hour urinary metanephrine levels. The sensitivity and specificity rates for plasma metanephrine were 80-92% and 92-96%, respectively; while for 24-hour urinary metanephrine were 80-90% and 95-100%, respectively. We found a strong positive relationship between the tumor size and the plasma levels of normetanephrine (r=0.518, p<0.01), and metanephrine (r=0.577, p<0.01). While the relation with the 24-hour urinary concentrations of normetanephrine (r=0.384, p=0.01) and 24-h urinary meta-nephrine (r=0.138, p<0.01) was low. The determination of plasma and 24-hour urinary levels of metanephrines is a reliable test for the diagnosis of PHEO, as they are continuously produced by the tumor cells in contrast to catecholamines.
Topics: Humans; Pheochromocytoma; Metanephrine; Normetanephrine; Adrenal Gland Neoplasms; Paraganglioma
PubMed: 37715982
DOI: 10.2478/enr-2023-0022 -
Praxis Aug 2018CME: Pheochromocytoma in the General Practice Abstract. Pheochromocytoma are rare tumors, usually symptomatic due to their hormonal activity with excessive catecholamine... (Review)
Review
CME: Pheochromocytoma in the General Practice Abstract. Pheochromocytoma are rare tumors, usually symptomatic due to their hormonal activity with excessive catecholamine secretion. Because of their bright spectrum of clinical presentation, they are often undiagnosed. The first diagnostic step is biochemical screening with measurement of free metanephrines in plasma or fractionated metanephrines in 24-hours urine. Knowledge about measurement method used and potential preanalytical factors leading to false results, are necessary for the interpretation. Tumor localisation (imaging) is performed after biochemical evidence of the tumor is present. Laparoscopic surgery is for the majority of cases the primary therapy and curative. Lifelong biochemical follow-up is necessary, with additional tests in case of hereditary tumors.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Diagnosis, Differential; Humans; Laparoscopy; Magnetic Resonance Imaging; Male; Mass Screening; Metanephrine; Middle Aged; Normetanephrine; Pheochromocytoma; Tomography, X-Ray Computed
PubMed: 30131024
DOI: 10.1024/1661-8157/a003047 -
Clinical Chemistry Jan 1981A radioimmunoassay involving an 125I ligand has been developed and applied to the measurement of urinary metanephrine. To validate the clinical usefulness of this assay,... (Comparative Study)
Comparative Study
A radioimmunoassay involving an 125I ligand has been developed and applied to the measurement of urinary metanephrine. To validate the clinical usefulness of this assay, we compared measurement of metanephrine by radioimmunoassay and of total urinary metanephrines by the Pisano colorimetric method. The radioimmunoassay is specific for metanephrine, whereas the colorimetric method measures both metanephrine and normetanephrine. We used both methods to determine urinary metanephrine or total metanephrines in subjects with essential hypertension, pheochromocytoma, the syndrome of multiple endocrine adenomatosis type 2, and normotensive volunteers. The mean and upper limit of normal (3 SD) for metanephrine by radioimmunoassay in our normotensive volunteers was 94.2 microgram/24 h and 229 microgram/24 h, respectively, which compares well with reported values of 87.6 microgram/24 h and 319 microgram/24 h by non-radioimmunoassay methods. Both radioimmunoassay and colorimetry accurately identified five patients with known pheochromocytoma. Good correlation (r = 0.993) was demonstrated between the two assays in a comparison of patients with essential hypertension and pheochromocytoma. We conclude that the radioimmunoassay is at least equivalent to the colorimetric methods in distinguishing pathological and normal catecholamine secretion, and is faster, more precise, and 1000-fold more sensitive.
Topics: Adrenal Gland Neoplasms; Adult; Child; Colorimetry; Diagnosis, Differential; Epinephrine; Humans; Hypertension; Metanephrine; Multiple Endocrine Neoplasia; Neuroblastoma; Pheochromocytoma; Radioimmunoassay
PubMed: 6108804
DOI: No ID Found -
Endocrine-related Cancer Jan 2024Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a... (Observational Study)
Observational Study
Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.
Topics: Humans; Pheochromocytoma; Normetanephrine; Antidepressive Agents, Tricyclic; Selective Serotonin Reuptake Inhibitors; Metanephrine; Paraganglioma; Norepinephrine; Adrenal Gland Neoplasms
PubMed: 37955319
DOI: 10.1530/ERC-23-0063 -
Hypertension (Dallas, Tex. : 1979) Mar 2024Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and...
BACKGROUND
Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype.
METHODS
We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines.
RESULTS
According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; =0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; =0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis.
CONCLUSIONS
We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
Topics: Humans; Pheochromocytoma; Retrospective Studies; Paraganglioma; Catecholamines; Metanephrine; Myocardial Infarction; Adrenal Gland Neoplasms; Adrenergic Agents; Phenotype; Atherosclerosis; Cardiomyopathies
PubMed: 38152977
DOI: 10.1161/HYPERTENSIONAHA.123.21902