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Best Practice & Research. Clinical... Mar 2020Pheochromocytomas are rare neuroendocrine chromaffin-derived tumors that arise within the adrenal medulla. They are usually benign, but if not diagnosed or if left... (Review)
Review
Pheochromocytomas are rare neuroendocrine chromaffin-derived tumors that arise within the adrenal medulla. They are usually benign, but if not diagnosed or if left untreated, they can have devastating consequences. Clinical consideration of the diagnosis is paramount, as they may have protean manifestations, and a high index of suspicion is essential if serious consequences are to be avoided. An accurate biochemical diagnosis is crucial for the management of these patients: either plasma or urinary metanephrines are both highly sensitive and specific if correctly employed, but knowledge of pre- and post-analytic interference is essential. Diagnostic imaging with cross-sectional CT and/or MRI offers high sensitivity in their detection, but lack specificity. The introduction of PET/CT/MR has led to a dramatic improvement in the localization of both pheochromocytomas and paragangliomas, together with the increasing availability of new functional imaging radionuclides. Optimal investigation and accurate diagnosis is best achieved at 'centers of excellence' with expert multidisciplinary teams.
Topics: Adrenal Gland Neoplasms; Blood Chemical Analysis; Cross-Sectional Studies; Diagnostic Techniques, Endocrine; Humans; Magnetic Resonance Imaging; Metanephrine; Pheochromocytoma; Positron Emission Tomography Computed Tomography; Sensitivity and Specificity; Urinalysis
PubMed: 31708376
DOI: 10.1016/j.beem.2019.101346 -
Endocrine Reviews Sep 2023Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once...
Pheochromocytoma and paraganglioma (PPGL) require prompt consideration and efficient diagnosis and treatment to minimize associated morbidity and mortality. Once considered, appropriate biochemical testing is key to diagnosis. Advances in understanding catecholamine metabolism have clarified why measurements of the O-methylated catecholamine metabolites rather than the catecholamines themselves are important for effective diagnosis. These metabolites, normetanephrine and metanephrine, produced respectively from norepinephrine and epinephrine, can be measured in plasma or urine, with choice according to available methods or presentation of patients. For patients with signs and symptoms of catecholamine excess, either test will invariably establish the diagnosis, whereas the plasma test provides higher sensitivity than urinary metanephrines for patients screened due to an incidentaloma or genetic predisposition, particularly for small tumors or in patients with an asymptomatic presentation. Additional measurements of plasma methoxytyramine can be important for some tumors, such as paragangliomas, and for surveillance of patients at risk of metastatic disease. Avoidance of false-positive test results is best achieved by plasma measurements with appropriate reference intervals and preanalytical precautions, including sampling blood in the fully supine position. Follow-up of positive results, including optimization of preanalytics for repeat tests or whether to proceed directly to anatomic imaging or confirmatory clonidine tests, depends on the test results, which can also suggest likely size, adrenal vs extra-adrenal location, underlying biology, or even metastatic involvement of a suspected tumor. Modern biochemical testing now makes diagnosis of PPGL relatively simple. Integration of artificial intelligence into the process should make it possible to fine-tune these advances.
Topics: Humans; Pheochromocytoma; Artificial Intelligence; Paraganglioma; Metanephrine; Adrenal Gland Neoplasms
PubMed: 36996131
DOI: 10.1210/endrev/bnad011 -
Experimental and Clinical Endocrinology... Oct 2007In recent years, liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as an innovative analytical technology applicable to a wide number of analyses in... (Review)
Review
In recent years, liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as an innovative analytical technology applicable to a wide number of analyses in the endocrinology laboratory. Compared to the "traditional" technique of gas chromatography-mass spectrometry (GC-MS), LC-MS/MS is easier to use and is applicable for a substantially larger number of relevant analytes. With the development of LC-MS/MS, the widespread application of the proven principle of isotope dilution mass spectrometry is now feasible not only in research but also for routine applications. The aim of this review is to explain the basic technical principles of LC-MS/MS, to describe the general characteristics of analytical LC-MS/MS applications and to comprehensively discuss the application of this technology in the field of endocrinology.
Topics: 17-alpha-Hydroxyprogesterone; Calcifediol; Chromatography, Liquid; Endocrinology; Humans; Hydrocortisone; Metanephrine; Tandem Mass Spectrometry; Testosterone
PubMed: 17943689
DOI: 10.1055/s-2007-981458 -
The New England Journal of Medicine May 2021
Topics: Adrenal Gland Neoplasms; Arthroplasty, Replacement, Knee; Echocardiography; Electrocardiography; Fatal Outcome; Heart Arrest; Humans; Hypertension; Lung; Male; Metanephrine; Middle Aged; Pheochromocytoma; Radiography, Thoracic; Stroke Volume; Tachycardia; Takotsubo Cardiomyopathy
PubMed: 34042392
DOI: 10.1056/NEJMimc2031595 -
Clinics in Laboratory Medicine Mar 2004Pheochromocytoma is a lethal tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with the symptoms of palpitations, severe headaches,... (Review)
Review
Pheochromocytoma is a lethal tumor of chromaffin cells of the adrenal medulla that produces episodes of hypertension with the symptoms of palpitations, severe headaches, and sweating. The diagnosis of pheochromocytoma is a challenging one; autopsy series suggest that many pheochromocytomas are not clinically suspected, and the undiagnosed tumor can be associated with morbid consequences. The testing of catecholamines, metanephrines, and Vanillylymandelic acid commonly is used for screening of pheochromocytoma. The diagnostic value of various biochemical tests,as reported in recent Mayo and National Institutes of Health studies, have been compared and discussed in detail. The recent developments in the methodologies of metanephrines testing also are presented.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Chemistry, Clinical; Humans; Metanephrine; Pheochromocytoma
PubMed: 15157558
DOI: 10.1016/j.cll.2004.01.015 -
Endocrinology and Metabolism Clinics of... Sep 2019Pheochromocytoma during pregnancy, although rare, is a perilous condition. The wellbeing of mother and fetus are at stake if not diagnosed and treated antenatally and... (Review)
Review
Pheochromocytoma during pregnancy, although rare, is a perilous condition. The wellbeing of mother and fetus are at stake if not diagnosed and treated antenatally and timely. The diagnosis is frequently overlooked because of the aspecific nature of signs and symptoms and confusion with pregnancy-related hypertension. Measurements of plasma or urinary free metanephrines have the highest diagnostic accuracy. MRI is preferred over ultrasonography. The optimal time for surgical removal is before 24 weeks of gestation or at/after delivery. Laparoscopic adrenalectomy should be preceded by medical pretreatment. Cesarean delivery is preferred in these patients; vaginal delivery might be considered in selected pretreated patients.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Female; Humans; Magnetic Resonance Imaging; Metanephrine; Pheochromocytoma; Pregnancy; Pregnancy Complications, Neoplastic; Ultrasonography
PubMed: 31345526
DOI: 10.1016/j.ecl.2019.05.006 -
Journal of Endocrinological... Jan 2020Urinary metanephrine is a reliable method to estimate catecholamine secretion. Traditionally, urinary metanephrines are collected into chilled containers containing...
BACKGROUND
Urinary metanephrine is a reliable method to estimate catecholamine secretion. Traditionally, urinary metanephrines are collected into chilled containers containing hydrochloric acid (HCl) and most laboratories freeze urinary samples before analysis. It is uncertain if these pre-analytic procedures alter metanephrine values.
AIM
To evaluate if acidifying and freezing urine samples affect the accuracy of urinary metanephrine measurements.
METHODS
Random urine samples from healthy individuals were collected. Urine samples were distributed into two containers: with HCl 50% homogenized with urine to obtain pH < 2, and without HCl. Each container was divided again into aliquots for immediate measurement or freezing. One aliquot with acid (group 1) and another without acid (group 2) were sent immediately to the laboratory for testing (HPLC), while the other two aliquots, one with acid (group 3) and another without it (group 4) were frozen for 3 months at - 20 °C. Bland-Altman's test was used to analyze inter-assay agreement between measurements.
RESULTS
A total of 15 individuals were included (mean age 27.5 ± 5.9 years, 8 male and 14 white). No difference was observed on mean urinary metanephrine/creatinine ratio between groups: group 1: 0.23 ± 0.11, group 2: 0.22 ± 0.07, group 3: 0.25 ± 0.13, group 4: 0.25 ± 0.15 mg/g creatinine; P > 0.05 for all the comparisons). Bland-Altman's analysis showed agreement between the standard method (group 1) and the experimental method (group 4).
CONCLUSION
Measurement of urinary metanephrines by HPLC method is not influenced by sample acidification nor freezing at - 20 °C for 3 months.
Topics: Acids; Adult; Female; Freezing; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Male; Metanephrine; Specimen Handling
PubMed: 31228104
DOI: 10.1007/s40618-019-01076-9 -
The Journal of Clinical Endocrinology... Aug 2023Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the...
CONTEXT
Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis.
OBJECTIVE
We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index.
METHODS
We retrospectively included 101 patients with PA who underwent AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both unstimulated and cosyntropin-stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol to metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone to metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared with aldosterone to cortisol (A/C) LI.
RESULTS
Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of unilateral PA with A/M LI instead of bilateral PA with A/C LI and 5% had a diagnosis of bilateral PA with A/M LI instead of unilateral PA.
CONCLUSION
The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion.
Topics: Humans; Aldosterone; Hyperaldosteronism; Hydrocortisone; Metanephrine; Retrospective Studies; Prevalence; Veins; Adrenal Glands
PubMed: 36974473
DOI: 10.1210/clinem/dgad179 -
Biomedical Microdevices Feb 2016Neuroendocrine tumors, such as pheochromocytoma or paraganglioma, are dangerous tumors that constitute a potential threat for a large number of patients. Currently, the...
Neuroendocrine tumors, such as pheochromocytoma or paraganglioma, are dangerous tumors that constitute a potential threat for a large number of patients. Currently, the biochemical diagnosis of neuroendocrine tumors is based on measurement of the direct secretory products of the adrenomedullary-sympathetic system or of their metabolites, such as catecholamines or their metanephrine derivatives, from plasma or urine. The techniques used for analysis of plasma free metanephrines, i.e. high-performance liquid chromatography or high-performance liquid chromatography coupled with mass-spectrometry are technically-demanding and time consuming, which limit their availability. Here we demonstrate a simple, fast and low-cost method for detecting metanephrine by Surface Enhanced Raman Scattering (SERS). The protocol consists in using evaporation-induced self-assembly of gold (Au) nanoparticles incubated with the analyte, on planar gold films. The assembly process produces regions with a dense distribution of both inter-particle gaps and particle-film gaps. Finite-difference time-domain simulations confirm that both kinds of gaps are locations of enhanced electromagnetic fields resulting from inter-particle and particle-film plasmonic coupling, useful for SERS amplification. Metanephrine vibrational bands assignment was performed according to density functional theory calculations. Metanephrine metabolite was detected in liquid at concentration levels lower than previously reported for other similar metabolites. The obtained results demonstrate that the Au nanoparticle/Au film exhibits noticeable SERS amplification of the adsorbed metabolite and can be used in the design of efficient, stable SERS-active substrates for the detection and identification of specific tumor markers.
Topics: Adrenal Gland Neoplasms; Biomarkers; Gold; Humans; Metal Nanoparticles; Metanephrine; Pheochromocytoma; Spectrum Analysis, Raman
PubMed: 26820563
DOI: 10.1007/s10544-016-0037-3 -
Nihon Rinsho. Japanese Journal of... Mar 1995
Review
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Metanephrine; Normetanephrine
PubMed: 8753293
DOI: No ID Found