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Polish Archives of Internal Medicine Mar 2024Incidentaloma is an adrenal tumor detected during diagnostic imaging performed for extra‑adrenal causes. Evaluation of metanephrine concentrations in a 24‑hour urine...
INTRODUCTION
Incidentaloma is an adrenal tumor detected during diagnostic imaging performed for extra‑adrenal causes. Evaluation of metanephrine concentrations in a 24‑hour urine collection can be a significant challenge in patients with multiple medications and comorbidities.
OBJECTIVES
The aim of this study was to evaluate the effect of commonly used groups of drugs on metanephrine levels in the 24‑hour urine collection.
PATIENTS AND METHODS
A total of 1051 patients with adrenal mass below 10 Hounsfield units on unenhanced computed tomography were included in the study. Patients diagnosed with Cushing or Conn syndrome, adrenal carcinoma, pheochromocytoma, active extra‑adrenal malignant neoplasms, and exacerbation of severe illnesses were excluded. Metanephrine, normetanephrine, and 3‑methoxytyramine in the 24‑hour urine collection were measured by high‑performance liquid chromatography with electrochemical detection. Information on concomitant medication (β‑blockers, calcium channel blockers [CCBs], loop diuretics, thiazide diuretics, potassium‑sparing diuretics, α‑blockers, angiotensin‑converting enzyme inhibitors / angiotensin II receptor blockers, metformin, nonmetformin antidiabetic drugs [NMADs], lipid‑lowering drugs, proton pump inhibitors, levothyroxine, thyreostatics, antidepressants, neuroleptics, benzodiazepines, glucocorticosteroids, inhaled B‑receptor agonists, and ipratropium) was collected from each patient.
RESULTS
The urinary excretion of normetanephrine was significantly higher in the patients on β‑blockers, CCBs, loop diuretics, α‑blockers, NMADs, and neuroleptics. α‑Blockers increased urine metanephrine concentration, and NMADs, antidepressants, and glucocorticosteroids lowered it. There was no association between the analyzed drugs and urinary 3‑methoxytyramine level.
CONCLUSIONS
Many drug groups interfere with the measurement of urinary fractionated metanephrines. These interactions should be taken into account during interpretation of a hormonal evaluation, as they can be crucial for further management, especially for making a decision on surgical treatment.
Topics: Humans; Metanephrine; Normetanephrine; Antipsychotic Agents; Adrenal Gland Neoplasms; Antidepressive Agents; Diuretics; Dopamine
PubMed: 38164744
DOI: 10.20452/pamw.16646 -
Archives of Surgery (Chicago, Ill. :... Sep 2007To assess the risk of pheochromocytoma in patients with borderline-elevated urine or plasma metanephrine levels.
OBJECTIVE
To assess the risk of pheochromocytoma in patients with borderline-elevated urine or plasma metanephrine levels.
DESIGN
Retrospective review.
SETTING
University tertiary care center.
PATIENTS
Forty-two consecutive patients with adrenal incidentalomas (defined as adrenal tumors identified during routine imaging for another condition) who were treated at the UCSF (University of California, San Francisco) Medical Center between January 1, 1995, and July 31, 2005. Patients with genetic syndromes were excluded.
INTERVENTION
Laparoscopic adrenalectomy for adrenal incidentaloma based on size criteria and preoperative hormonal test results.
MAIN OUTCOMES MEASURES
Urine or plasma metanephrine and catecholamine levels, tumor size, and presence of pheochromocytoma.
RESULTS
Of 42 patients, 14 (33%) had a pheochromocytoma (11 of whom had clear-cut elevations in urine or plasma metanephrine levels defined as greater than 2 times the upper limit of normal) and 28 did not. Ten of the 42 patients (24%) had borderline elevations in urine or plasma metanephrine levels (defined as 1-2 times the upper limit of normal), 3 of whom had a pheochromocytoma (30%). Of patients with borderline elevations, mean +/- SD tumor size was 5.4 +/- 3.1 and 4.8 +/- 1.9 cm for patients with and without pheochromocytoma, respectively (P = .37). In these 10 patients, no clinical factors (age, sex, hypertension, presence of symptoms, number of antihypertensive medications, preoperative hemodynamics, or size of tumor on computed tomographic scan) allowed differentiation between those with and without pheochromocytoma.
CONCLUSIONS
Thirty percent of patients with adrenal incidentaloma and borderline-elevated urine or plasma metanephrine levels had a pheochromocytoma. Clinical factors cannot distinguish between those with and without pheochromocytoma. In this group of patients, we advocate either routine alpha-blockade preoperatively or further diagnostic tests to better characterize the tumor.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Chi-Square Distribution; Female; Humans; Incidental Findings; Laparoscopy; Male; Metanephrine; Pheochromocytoma; Predictive Value of Tests; Retrospective Studies; Treatment Outcome
PubMed: 17875842
DOI: 10.1001/archsurg.142.9.870 -
Experientia May 1985Both normetanephrine and metanephrine were found to be oxidized by both types of monoamine oxidase in mouse liver mitochondria. Both Km and Vmax values of type B MAO for...
Both normetanephrine and metanephrine were found to be oxidized by both types of monoamine oxidase in mouse liver mitochondria. Both Km and Vmax values of type B MAO for both substrates were higher than those of type A MAO, which caused the shift of inhibition curves with clorgyline and deprenyl according to the increase in substrate concentration.
Topics: Animals; Epinephrine; Isoenzymes; Kinetics; Male; Metanephrine; Mice; Mice, Inbred Strains; Mitochondria, Liver; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Normetanephrine; Substrate Specificity
PubMed: 3996536
DOI: 10.1007/BF02007695 -
Annales D'endocrinologie Jun 2020In routine hormonology, liquid chromatography mass spectrometry (LCMS) is now an established technique for androgen, urinary cortisol and metanephrine assay. It has the... (Review)
Review
In routine hormonology, liquid chromatography mass spectrometry (LCMS) is now an established technique for androgen, urinary cortisol and metanephrine assay. It has the undeniable advantage of great analytical specificity, but with sensitivity that clearly depends on financial investment in a very high-end spectrometer. We describe the general principles of LCMS and the routine applications so far developed in hormonology. The purpose is to familiarise endocrinologists with the techniques under development and their pros and cons.
Topics: Androgens; Chromatography, Liquid; Diagnostic Techniques, Endocrine; Diagnostic Tests, Routine; Education, Medical, Continuing; Endocrinologists; Humans; Hydrocortisone; Mass Spectrometry; Metanephrine
PubMed: 32340850
DOI: 10.1016/j.ando.2020.03.021 -
FP Essentials Nov 2018Incidentally discovered adrenal masses, referred to as adrenal incidentalomas, are fairly common given the routine use of imaging as part of clinical care in a variety... (Review)
Review
Incidentally discovered adrenal masses, referred to as adrenal incidentalomas, are fairly common given the routine use of imaging as part of clinical care in a variety of settings. Adrenal incidentalomas most frequently are benign and hormonally inactive tumors. However, approximately 11% to 15% are hormonally active, which can lead to diagnosis of clinically relevant conditions that affect morbidity and mortality. Thus, all adrenal incidentalomas should be tested for production of hormones at initial diagnosis. A 1-mg dexamethasone suppression test is the initial screening test. Patients then should be referred for appropriate treatment. Among the adrenal mass subtypes, pheochromocytomas are associated with the highest risk of mortality. Every effort should be made to exclude the presence of these tumors. Patients with hypertension and adrenal incidentalomas should be evaluated for aldosterone excess with an aldosterone to renin ratio. Primary malignancy represents a low percentage of adrenal incidentalomas. A minority of adrenal malignancies are primary adrenocortical tumors, which are associated with a poor prognosis and for which management often is palliative.
Topics: Adrenal Gland Neoplasms; Adrenal Glands; Aged; Aldosterone; Biopsy; Catecholamines; Dexamethasone; Endocrine System Diseases; Female; Humans; Incidental Findings; Magnetic Resonance Imaging; Male; Metanephrine; Renin; Tomography Scanners, X-Ray Computed
PubMed: 30427650
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Jul 2010
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Child; Child, Preschool; Humans; Infant; Metanephrine; Neuroblastoma; Normetanephrine; Peripheral Nervous System Neoplasms; Pheochromocytoma; Sympathetic Nervous System
PubMed: 20963883
DOI: No ID Found -
Clinical Chemistry Sep 2007Quantification of plasma free metanephrine (MN) and normetanephrine (NMN) is considered to be the most accurate test for the clinical chemical diagnosis of... (Comparative Study)
Comparative Study
BACKGROUND
Quantification of plasma free metanephrine (MN) and normetanephrine (NMN) is considered to be the most accurate test for the clinical chemical diagnosis of pheochromocytoma and follow-up of pheochromocytoma patients. Current methods involve laborious, time-consuming, offline sample preparation, coupled with relatively nonspecific detection. Our aim was to develop a rapid, sensitive, and highly selective automated method for plasma free MNs in the nanomole per liter range.
METHODS
We used online solid-phase extraction coupled with HPLC-tandem mass spectrometric detection (XLC-MS/MS). Fifty microliters plasma equivalent was prepurified by automated online solid-phase extraction, using weak cation exchange cartridges. Chromatographic separation of the analytes and deuterated analogs was achieved by hydrophilic interaction chromatography. Mass spectrometric detection was performed in the multiple reaction monitoring mode using a quadrupole tandem mass spectrometer in positive electrospray ionization mode.
RESULTS
Total run-time including sample cleanup was 8 min. Intra- and interassay analytical variation (CV) varied from 2.0% to 4.7% and 1.6% to 13.5%, respectively, whereas biological intra- and interday variation ranged from 9.4% to 45.0% and 8.4% to 23.2%. Linearity in the 0 to 20 nmol/L calibration range was excellent (R(2) > 0.99). For all compounds, recoveries ranged from 74.5% to 99.6%, and detection limits were <0.10 nmol/L. Reference intervals for 120 healthy adults were 0.07 to 0.33 nmol/L (MN), 0.23 to 1.07 nmol/L (NMN), and <0.17 nmol/L (3-methoxytyramine).
CONCLUSIONS
This automated high-throughput XLC-MS/MS method for the measurement of plasma free MNs is precise and linear, with short analysis time and low variable costs. The method is attractive for routine diagnosis of pheochromocytoma because of its high analytical sensitivity, the analytical power of MS/MS, and the high diagnostic accuracy of free MNs.
Topics: Adrenal Gland Neoplasms; Adult; Autoanalysis; Blood Proteins; Chromatography, High Pressure Liquid; Humans; Metanephrine; Pheochromocytoma; Protein Binding; Quality Control; Reference Values; Sensitivity and Specificity; Solid Phase Extraction; Tandem Mass Spectrometry
PubMed: 17712005
DOI: 10.1373/clinchem.2007.087114 -
Frontiers in Endocrinology 2022Catecholamine-producing tumors of childhood include most notably neuroblastoma, but also pheochromocytoma and paraganglioma (PPGL). Diagnosis of the former depends... (Review)
Review
Catecholamine-producing tumors of childhood include most notably neuroblastoma, but also pheochromocytoma and paraganglioma (PPGL). Diagnosis of the former depends largely on biopsy-dependent histopathology, but this is contraindicated in PPGL where diagnosis depends crucially on biochemical tests of catecholamine excess. Such tests retain some importance in neuroblastoma though continue to largely rely on measurements of homovanillic acid (HVA) and vanillylmandelic acid (VMA), which are no longer recommended for PPGL. For PPGL, urinary or plasma metanephrines are the recommended most accurate tests. Addition of methoxytyramine to the plasma panel is particularly useful to identify dopamine-producing tumors and combined with normetanephrine also shows superior diagnostic performance over HVA and VMA for neuroblastoma. While use of metanephrines and methoxytyramine for diagnosis of PPGL in adults is established, there are numerous pitfalls for use of these tests in children. The establishment of pediatric reference intervals is particularly difficult and complicated by dynamic changes in metabolites during childhood, especially in infants for both plasma and urinary measurements, and extending to adolescence for urinary measurements. Interpretation of test results is further complicated in children by difficulties in following recommended preanalytical precautions. Due to this, the slow growing nature of PPGL and neglected consideration of the tumors in childhood the true pediatric prevalence of PPGL is likely underappreciated. Earlier identification of disease, as facilitated by surveillance programs, may uncover the true prevalence and improve therapeutic outcomes of childhood PPGL. For neuroblastoma there remain considerable obstacles in moving from entrenched to more accurate tests of catecholamine excess.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Child; Humans; Infant; Metanephrine; Neuroblastoma; Paraganglioma; Pheochromocytoma
PubMed: 35957826
DOI: 10.3389/fendo.2022.901760 -
The New England Journal of Medicine Jun 1999The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel-Lindau disease or multiple endocrine neoplasia type 2 (MEN-2),...
BACKGROUND
The detection of pheochromocytomas in patients at risk for these tumors, such as patients with von Hippel-Lindau disease or multiple endocrine neoplasia type 2 (MEN-2), is hindered by the inadequate sensitivity of commonly available biochemical tests. In this study we evaluated measurements of plasma normetanephrine and metanephrine for detecting pheochromocytomas in patients with von Hippel-Lindau disease or MEN-2.
METHODS
We studied 26 patients with von Hippel-Lindau disease and 9 patients with MEN-2 who had histologically verified pheochromocytomas and 50 patients with von Hippel-Lindau disease or MEN-2 who had no radiologic evidence of pheochromocytoma. Von Hippel-Lindau disease and MEN-2 were diagnosed on the basis of germ-line mutations of the appropriate genes. The plasma concentrations of normetanephrine and metanephrine were compared with the plasma concentrations of catecholamines (norepinephrine and epinephrine) and urinary excretion of catecholamines, metanephrines, and vanillylmandelic acid.
RESULTS
The sensitivity of measurements of plasma normetanephrine and metanephrine for the detection of tumors was 97 percent, whereas the other biochemical tests had a sensitivity of only 47 to 74 percent. All patients with MEN-2 had high plasma concentrations of metanephrine, whereas the patients with von Hippel-Lindau disease had almost exclusively high plasma concentrations of only normetanephrine. One patient with von Hippel-Lindau disease had a normal plasma normetanephrine concentration; this patient had a very small adrenal tumor (<1 cm). The high sensitivity of measurements of plasma normetanephrine and metanephrine was accompanied by a high level of specificity (96 percent).
CONCLUSIONS
Measurements of plasma normetanephrine and metanephrine are useful in screening for pheochromocytomas in patients with a familial predisposition to these tumors.
Topics: Adolescent; Adult; Aged; Epinephrine; Female; Humans; Male; Metanephrine; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Norepinephrine; Normetanephrine; Pheochromocytoma; Sensitivity and Specificity; Vanilmandelic Acid; von Hippel-Lindau Disease
PubMed: 10369850
DOI: 10.1056/NEJM199906173402404 -
Biochimica Et Biophysica Acta Oct 1958
Topics: Biochemical Phenomena; Epinephrine; Humans; Metanephrine
PubMed: 13584415
DOI: 10.1016/0006-3002(58)90259-2