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]; P=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]; P=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.
- MeSH
- Adrenergic Agents MeSH
- Atherosclerosis * complications MeSH
- Phenotype MeSH
- Pheochromocytoma * diagnosis MeSH
- Myocardial Infarction * MeSH
- Cardiomyopathies * MeSH
- Catecholamines MeSH
- Humans MeSH
- Metanephrine MeSH
- Adrenal Gland Neoplasms * pathology MeSH
- Paraganglioma * complications MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma. METHODS: Twenty-four-hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FD) and/or ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS). RESULTS: Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24-hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24-hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver-operating-characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods. CONCLUSION: Catecholamine metabolites in spot urine and 24-hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.
- MeSH
- Chromatography, Liquid methods MeSH
- Homovanillic Acid urine MeSH
- Vanilmandelic Acid urine MeSH
- Humans MeSH
- Metanephrine urine MeSH
- Neuroblastoma * diagnosis MeSH
- Tandem Mass Spectrometry * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
V předkládané kazuistice popisujeme vzácný případ pacientky s feochromocytomem produkujícím adrenokortikotropní hormon (ACTH). Tento ektopicky produkovaný ACTH stimuloval kontralaterální nadledvinu ke zvýšené produkci kortikoidů a vyvolal Cushingův syndrom. Podezření na tuto diagnózu bylo vysloveno na základě laboratorního vyšetření (opakovaná hypokalemie a metabolická alkalóza) a definitivně bylo potvrzeno po histopatologickém, histochemickém a imunohistochemickém vyšetření nádoru.
We present a case of a patient with pheochromocytoma producing adrenocorticotropic hormone (ACTH). This ectopically produced ACTH stimulated the contralateral adrenal to produce higher amounts of corticoids and it led to Cushing's syndrome. Suspicion of this diagnosis was based on laboratory results (hypokalemia and metabolic acidosis) and definitely confirmed after histopathological, histochemical and immunohistochemical examination of tumour.
- MeSH
- Adrenalectomy MeSH
- Adrenocorticotropic Hormone analysis MeSH
- Adrenergic alpha-Antagonists therapeutic use MeSH
- Potassium Chloride administration & dosage MeSH
- Adult MeSH
- Pheochromocytoma * surgery diagnostic imaging complications physiopathology MeSH
- Hydrocortisone analysis MeSH
- Pituitary ACTH Hypersecretion * surgery diagnosis etiology complications MeSH
- Hypokalemia etiology MeSH
- Clinical Chemistry Tests statistics & numerical data MeSH
- Humans MeSH
- Metanephrine analysis MeSH
- Adrenal Gland Neoplasms surgery diagnostic imaging complications physiopathology MeSH
- Spironolactone administration & dosage MeSH
- Treatment Outcome MeSH
- Rare Diseases surgery diagnostic imaging complications physiopathology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
This work discusses the clinical performance of chromogranin A, free metanephrine and normetanephrine determination in plasma using a radioimmunoanalytical methods for the diagnosis of pheochromocytoma and paraganglioma. Blood samples were collected from 55 patients (46 pheochromocytomas, 9 paragangliomas). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The comparative group without a diagnosis of pheochromocytoma/paraganglioma consisted of 36 pheochromocytoma/paraganglioma patients more than 4 months after adrenal gland surgery, and of 87 patients, 16 of them with multiple endocrine neoplasia, 9 with medullary and 5 with parafolicullar carcinoma of the thyroid gland. The rest were patients with various adrenal gland disorders. Chromogranin A, metanephrine and normetanephrine were determined in the EDTA-plasma using a radioimmunoassay kits Cisbio Bioassays, France and IBL International GmbH, Germany. Clinical sensitivity was 96 % for the combination of metanephrine and normetanephrine, and 93 % for chromogranin A. Clinical specificity was 100 % for the combination metanephrine and normetanephrine, and 96 % for chromogranin A. Falsely elevated levels of chromogranin A were observed in 1 patient with chronic renal insufficiency and 9 analyses were influenced by the administration of proton pump inhibitors. These results were excluded of CGA specificity. Both the combination of plasma free metanephrine, normetanephrine and chromogranin A as determined by radioimmunoassays, which are simple without the necessity of special laboratory material, are effective markers of pheochromocytoma or paraganglioma. Chromogranin A exerts association to malignity and all markers are associated with tumor mass.
- MeSH
- Chromogranin A blood MeSH
- Adult MeSH
- Pheochromocytoma blood diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Metanephrine blood MeSH
- Adolescent MeSH
- Young Adult MeSH
- Biomarkers, Tumor blood MeSH
- Adrenal Gland Neoplasms blood diagnosis MeSH
- Normetanephrine blood MeSH
- Radioimmunoassay methods MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: The aim of this study was to assess the diagnostic value of catecholamines and their O-methylated metabolites in vitreous humor samples in identifying antemortem cold exposure and fatal hypothermia in the forensic casework. METHODS: A total of 80 autopsy cases (40 hypothermia fatalities and 40 cases in which hypothermia as the main or contributory cause of death was excluded) were selected for this study. Catecholamines and their O-methylated metabolites were measured in urine and vitreous humor samples collected at autopsy. RESULTS: Urine catecholamine and their O-methylated metabolite concentrations were significantly higher in hypothermia-related deaths. On the other hand, measurements in vitreous humor samples did not reveal statistically significant differences between hypothermia-related deaths and controls. CONCLUSIONS: Globally considered, our findings seem to suggest that, contrary to urine catecholamines and their O-methylated metabolites, vitreous levels of these compounds appear to be of limited value in characterizing human antemortem stress reactions due to cold exposure and can hardly be used in the forensic setting to support the diagnosis of hypothermia.
- MeSH
- Epinephrine metabolism MeSH
- Dopamine analogs & derivatives metabolism MeSH
- Adult MeSH
- Hypothermia diagnosis metabolism MeSH
- Catecholamines metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Metanephrine metabolism MeSH
- Young Adult MeSH
- Norepinephrine metabolism MeSH
- Normetanephrine metabolism MeSH
- Postmortem Changes MeSH
- Aged MeSH
- Vitreous Body metabolism MeSH
- Forensic Pathology MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Cíle studie: Vývoj a implementace metody stanovení volných metanefrinů v plazmě pomocí kapalinové chromatografie s tandemovou hmotnostní detekcí (LC-MS/MS) pro rutinní použití v diagnostické laboratoři, která eliminuje omezení klasické kapalinové (HPLC) nebo plynové chromatografie (GC) a imunoanalytických metod, jako jsou náročná příprava vzorků, derivatizace a interferující substance. Typ studie: Vývoj analytické metody. Posouzení vhodnosti pro rutinní použití v diagnostické laboratoři. Název a sídlo pracoviště: Laboratoř klinické biochemie – Oddělení instrumentálních metod, Spadia lab, a.s., Dr. Slabihoudka 6232/11, 708 52 Ostrava. Materiál a metody: Vývoj a validace metody byly provedeny na LC-MS/MS systému Agilent 6490 Triple Quadrupole. Pro chromatografickou separaci byla použita kolona SeQuant®ZIC®HILIC HPLC 3,5 mm, 100Å, PEEK 100 x 2,1 mm metalfree (Merck KGaA, Německo) a gradientová eluce. Pro stanovení analytických parametrů metody byly použity lyofilizované kalibrační a kontrolní materiály z firmy Recipe Chemicals and Instruments GmbH (Německo) a Chromsystems Instruments α Chemicals GmbH (Německo). Do studie bylo zařazeno 40 pacientů s diagnózou arteriální hypertenze. Výsledky: Analytické parametry nově vyvinuté metody jsou vyhovující. Variační koeficienty (CV) preciznosti v sérii a mezilehlá preciznost se pohybovaly pod 10%. Výtěžnost, určená metodou standardního přídavku se pohybovala v rozmezí 89 až 98%. Limit stanovitelnosti pro MN byl 0,035 nmol/l, pro NMN 0,049 nmol/l. Metoda splňuje požadavky validace pro oba analyty. Bylo provedeno srovnání tří metod stanovení volných metanefrinů v plazmě: 2-MET Plasma ELISAFast Track (Labor Diagnostika Nord GmbH, Něměcko), HPLC metoda s elektrochemickou detekcí (ECD) a komerčně dodávaná diagnostická souprava FEO Kit (VUOS a.s., Česká republika) a nově vyvinutá LC-MS/MS metoda. Statistická analýza byla provedena pomocí programu MedCalc 16.1 (Medcalc Software bvba, Belgie) s využitím Passing Bablokovy regresní analýzy. Závěr: Neuroendokrinní tumory představují heterogenní skupinu onemocnění s různou klinickou symptomatologií a etiopatogenezí. Neuroendokrinní tumory, jako jsou feochromocytom nebo paragangliom, vykazují setrvalou nebo paroxyzmální nadměrnou produkci katecholaminů. Jejich 3-O-methylované metabolity, metanefrin (MN) a normetanefrin (NMN), jsou preferovány pro diferenciální diagnostiku feochromocytomu vzhledem k jejich vysoké diagnostické senzitivitě a specificitě. Prezentovaná LC-MS/MS metoda eliminuje nevýhody klasických chromatografických technik a imunoanalytických metod, přičemž zásadními aspekty jsou: jednoduchá příprava vzorku, krátká doba analýzy a požadované analytické parametry.
Objective: The development and implementation of method for the determination of free metanephrines in plasma by the liquid chromatography tandem mass spectrometry (LC-MS/MS) suitable for routine practice in diagnostic laboratory which overcomes inconveniences related with classical liquid (HPLC) or gas chromatography (GC) and immunoassay approaches, like extensive sample preparation, the step of derivatization or interfering substances. Design: Analytical method development. Assessment of suitability for routine practice in diagnostic laboratory. Settings: Department of Clinical Biochemistry – Instrumental methods section, Spadia lab, a.s., Dr. Slabihoudka 6232/11, 708 52 Ostrava Material and Methods: Method development and validation were performed on Agilent 6490 Triple Quadrupole LC-MS/MS system. Chromatographic separation was achieved on SeQuant®ZIC®HILIC HPLC 3,5 µm, 100Å, PEEK 100 x 2,1 mm metal-free HPLC Column (Merck KGaA, Germany) by gradient elution. For determination of analytical parameters lyophilised plasma calibrators (purchased from RECIPE Chemicals and Instruments GmbH, Germany) and controls (purchased from Recipe Chemicals and Instruments GmbH and Chromsystems Instruments α Chemicals GmbH, Germany) were used. The study included 40 patients with diagnosis arterial hypertension. Results: The analytical performance of the new developed method is satisfactory. The intra-assay and inter-assay coefficients of variation (CV) were below 10%. Recoveries determined by standard addition were from 89 to 98%. The limit of quantification for MN was 0.035 nmol/l, for NMN was 0.049 nmol/l. This method fulfilled requirements for validation parameters for both analytes. Comparison of three methods for quantification of free metanephrines in plasma was performed– 2-MET Plasma ELISAFast Track (Labor Diagnostika Nord GmbH, Germany), FEO Kit (VUOS a.s., Czech Republic) dedicated for HPLC-ECD systems and developed LC-MS/MS method. Statistical analysis was performed using the MedCalc 16.1 (Medcalc Software bvba, Belgium) using the Passing Bablok regression. Conclusions: Neuroendocrine tumors represent a clinically and etiologically diverse group of disorders. Neuroendocrine tumors, such as pheochromocytomas or paragangliomas, exhibit a persistent or pyroxysmal excessive catecholamines production. 3-O-methylated catecholamine metabolites, metanephrine (MN) and normetanephrine (NMN), are prioritized for diagnosis of pheochromocytoma due to their highest diagnostic sensitivity and specificity. Presented LC-MS/MS method overcomes classical HPLC and immunoassay approaches. Method provides simple step of sample preparation, short runtime and required analytical parameters
- MeSH
- Early Detection of Cancer MeSH
- Chromatography, Liquid methods instrumentation MeSH
- Enzyme-Linked Immunosorbent Assay methods MeSH
- Pheochromocytoma diagnosis blood MeSH
- Mass Spectrometry methods instrumentation MeSH
- Metanephrine analysis blood MeSH
- Specimen Handling methods standards MeSH
- Reagent Kits, Diagnostic MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
1 svazek : ilustrace, tabulky ; 30 cm
Cirkulující chromogranin A je vhodným markerem feochromocytomu s asociací na malignitu a hmotu tumoru. Chromograniny, thyreoglobulin, "calcitonin gene-related" peptidy, metanefriny a thyreoidální hormony a faktory mohou vykazovat propojení s medulárním thyreoidálním karcinomem, se syndromem MEN 2 i s jinými typy neuroendokrinních tumorů. Nalezení vztahů mezi thyreoidálními faktory, sekretograniny, metanefriny a neuroendokrinními tumory pomocí postupů využívajích vícerozměrovou instrumentální analýzu a imunoanalytickou metodiku by mělo obohatit laboratorní diagnostiku medulárního karcinomu štítné žlázy , feochromocytomu a dalších neuroendokrinních tumorů.; The plasma chromogranin A is a suitable marker of pheochromocytoma with association to malignity and tumour mass. Chromogranins, thyroglobulin, calcitonin gene-related peptides, metanephrines, and thyroid hormones and factors can exert a connection to medullary thyroid carcinoma, MEN 2, and other neuroendocrine tumors. The localisation of associations among thyroid factors, secretogranins, metanephrines and neuroendocrine tumors using procedures of multidimensional instrumental analysis and immunoassaysshould be enhance laboratory diagnosis concerning mainly medullary thyroid carcinoma, pheochromocytoma, and other neuroendocrine tumors.
- MeSH
- Chromatography MeSH
- Chromogranins MeSH
- Pheochromocytoma MeSH
- Immunoenzyme Techniques MeSH
- Metanephrine MeSH
- Thyroid Neoplasms diagnosis MeSH
- Neuroendocrine Tumors diagnosis MeSH
- Receptors, Calcitonin Gene-Related Peptide MeSH
- Thyroglobulin MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- endokrinologie
- neurologie
- onkologie
- NML Publication type
- závěrečné zprávy o řešení grantu IGA MZ ČR
This work discusses the clinical performance of deconjugated metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3MT) determined in the basal first morning urine using a chromatographic method with electrochemical detection for the clinical diagnosis of pheochromocytoma (PHEO) and paraganglioma (PGL). Urine samples were collected from 44 patients (36 with PHEO, 8 with PGL) aged 54+/-17 (20-78) years (22 females, 22 males). A sampling of biological materials was performed preoperatively and about one week, six months and one year after adrenal gland surgery. The control group consisted of 34 PHEO/PGL patients more than 4 months after adrenal gland surgery. All subjects in the control group were without a diagnosis of PHEO or PGL. Clinical sensitivity was 55 % for MN, 64 % for NMN, 80 % for combination of both MN and NMN, and only 23 % for 3TM. Clinical specificity calculated from the control group was 93 % for MN, 95 % for NMN, 95 % for the combination MN and NMN, and 97 % for 3TM. Cut-off values for deconjugated metanephrines in the basal urine were 310 (MN), 690 (NMN) and 250 microg/l (3MT). Chromatographic determination of deconjugated urinary metanephrines, which is simple without the necessity of special laboratory material, can serve for the screening of PHEO or PGL patients. Urine NMN and 3MT exerts an association to malignity, and all markers are associated with tumor mass. However, the principal laboratory diagnosis of PHEO or PGL must be based on plasma-free metanephrines and plasma chromogranin A with better performance in the laboratory diagnosis of PHEO or PGL.
- MeSH
- Biomarkers urine MeSH
- Dopamine analogs & derivatives urine MeSH
- Adult MeSH
- Pheochromocytoma diagnosis urine MeSH
- Clinical Laboratory Techniques methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Metanephrine urine MeSH
- Young Adult MeSH
- Adrenal Gland Neoplasms diagnosis urine MeSH
- Normetanephrine urine MeSH
- Paraganglioma diagnosis urine MeSH
- Aged MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Feochromocytóm (FEO) a paraganglióm (PGL) sú neuroendokrinné tumory, ktoré vznikajú zo sympatických a parasympatických paraganglií. FEO sa najčastejšie prejavuje trvalou alebo záchvatovitou hypertenziou, bolesťami hlavy, potením, palpitáciami a úzkostnými stavmi. Diagnostika sa zakladá na typickom klinickom obraze a biochemickom potvrdení stanovením plazmatického normetanefrínu a metanefrínu, ktoré majú takmer 100% senzitivitu a sú vyšetrením voľby. Na lokalizáciu nádoru v bruchu a panve je metódou voľby počítačová tomografia (CT) alebo magnetická rezonancia (MRI). Definitívnou a kauzálnou liečbou je chirurgické odstránenie tumoru, a to preferenčne laparoskopicky. Hlavným cieľom predoperačnej liečby je normalizácia krvného tlaku, frekvencie srdca, obnova normovolémie a prevencia katecholamínovej „búrky“ a jej účinkov na kardiovaskulárny systém pri manipulácii s tumorom v priebehu operácie. Autori navrhujú pri hypertenznej kríze iniciálnu liečbu intravenóznym urapidilom, v prípade perzistujúcej tachykardie v kombinácii s perorálnym metoprololom podávaným s časovým posunom po dosiahnutí dostatočnej alfa blokády a/alebo s kalciovým blokátorom amlodipínom. Cieľom práce je upozorniť na úskalia v diagnostike feochromocytómu a ukázať možnosti súčasného predoperačného manažmentu, ktorý by mal zabrániť vážnym poškodeniam detí s FEO. Ošetrujúci lekár by mal rozpoznať a aktívne pátrať po týchto tumoroch, hlavne v kontexte známej genetickej predispozície (von Hippelovom-Lindauovom syndróme, mnohopočetnej endokrinnej neoplázii typu 2, pri neurofibromatóze typu 1 a paragangliómoch). Feochromocytóm nemusí vždy prebiehať pod typickým klinickým obrazom a preto je najdôležitejšou súčasťou jeho diagnostiky myslieť na túto možnosť a pri podozrení ju potvrdiť biochemicky.
Pheochromocytomas and paragangliomas (PHEO/PGL) are neuroendocrine tumors that arise from sympathetic and parasympathetic paraganglia. PHEO presents most frequently by permanent or paroxysmal hypertension, headache, sweating, palpitations and anxiety. Diagnosis is based on typical clinical presentation confirmed by biochemical measurement of plasma metanephrines and normetanephrines with the sensitivity almost up to 100% being the test of choice for the diagnosis of PHEO. The morphological test of choice is either computed tomography or magnetic resonance imaging, which have similar diagnostic sensitivities of the abdomen and pelvis. Definitive and causal treatment is by surgical resection and the procedure of choice for most PHEO is laparoscopic adrenalectomy. Main goal of preoperative management is normalization of blood pressure, heart rate, reinstitution of normovolemia and prevention of catecholamine „storm“ and its effects on cardiovascular system during manipulation with tumor in the course of operation. Authors suggest as initial treatment in hypertensive crisis intravenous urapidil and in case of persisting tachycardia the combination with metoprolol after adequate time delay to achieve satisfactory alpha blockade and/or calcium channel blocker amlodipine. The aim of the report is to draw attention to difficulties in diagnostics of PHEO and to outline current approaches to preoperative management to prevent severe adverse events of children suffering from this tumor. The pediatric provider should be able to recognize and screen for such tumors, particularly in the context of a known genetic predisposition (von Hippel-Lindau syndrome, MEN type 2, neurofibromatosis type 1, and paragangliomas). The clinical presentation of PHEO might be sometime atypical so most important part of correct diagnosis depends on having a clinical suspicion for it and then confirming the diagnosis biochemically.
- Keywords
- hypertenzní krize, urapidil, palpitace,
- MeSH
- Adrenalectomy MeSH
- Adrenergic alpha-1 Receptor Antagonists therapeutic use MeSH
- Antihypertensive Agents therapeutic use MeSH
- Headache etiology MeSH
- Child MeSH
- Pheochromocytoma * diagnosis surgery physiopathology MeSH
- Hypertension * etiology drug therapy MeSH
- Catecholamines metabolism MeSH
- Humans MeSH
- Metanephrine blood MeSH
- Normetanephrine blood MeSH
- Piperazines administration & dosage MeSH
- Sweating MeSH
- Preoperative Care MeSH
- Anxiety etiology MeSH
- von Hippel-Lindau Disease complications MeSH
- Check Tag
- Child MeSH
- Humans MeSH