Scoring system for diagnosis and pretreatment risk assessment of neuroblastoma using urinary biomarker combinations.

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3-methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography-mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2-penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high-risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.

Clinical Significance of Pheochromocytoma Size on the Timing and Extent of Surgery.

INTRODUCTION: Elevated metanephrine and catecholamine levels 3-fold upper limit of normal (ULN) are diagnostic for pheochromocytoma. We sought to determine whether size correlates with biochemical activity or symptoms which could guide timing of surgery. METHODS: Data from consecutive patients undergoing adrenalectomy for pheochromocytoma at our institution over a 10-year period were retrospectively collected. These included maximal lesion diameter on preoperative imaging, plasma/urine metanephrine and/or catecholamine levels, demographic variables and presence of typical paroxysmal symptoms. Receiver operating characteristic curves were used to assess predictive accuracy. RESULTS: Sixty-three patients were included in the analysis (41 females and 22 males). Median age was 56 (43, 69) years. Due to various referring practices, 31 patients had documented 24-h urine metanephrine, 26 had 24-h urine catecholamine, and 52 had fractionated plasma metanephrine levels available for review. Values were converted to fold change compared to ULN and the maximum of all measured values was used for logistic regression. Median tumor size was 3.40 (2.25, 4.55) cm in greatest dimension. Tumor size at which pheochromocytoma produced > 3-fold ULN was ≥2.3 cm (AUC of 0.84). Biochemical activity increased with doubling tumor size (odds ratio = 8, P = 0.0004) or ≥ 1 cm increase in tumor size (odds ratio = 3.03, P = 0.001). 40 patients had paroxysmal symptoms, but there was no significant correlation between tumor size/biochemical activity and symptoms. CONCLUSIONS: In our study, tumor size directly correlated with the degree of biochemical activity and pheochromocytomas ≥2.3 cm produced levels 3 times ULN. These findings may allow clinicians to adjust timing of operative intervention.

Factors Influencing Postmortem Catecholamine Level and Its Correlations With Agony Time and Cause of Death in Medicolegal Autopsy.

BACKGROUND: Catecholamines consisting of epinephrine (EP), norepinephrine (NE), and dopamine (DA) are known as a class of chemical neurotransmitters and hormones essential for regulation of physiological processes including stress responses. Many researchers have tried to establish a relationship between postmortem catecholamine level and agony time or underlying cause of death. However, relevant studies have yielded debatable results. This study was performed to determine characteristics of catecholamine distribution in postmortem specimens with various influencing factors and to assess relationships of postmortem catecholamine levels with agony time and cause of death. METHODS: A total of 114 autopsy cases were analyzed for catecholamine levels and EP/NE ratios in femoral blood, heart blood, and urine specimens. Postmortem catecholamine levels according to sex, age, medical treatments (cardiopulmonary resuscitation [CPR] and EP injection), postmortem interval (PMI), agonal period, manner of death, and cause of death were evaluated. RESULTS: Close mutual relationships were noted among femoral and heart blood catecholamine levels. There was no correlation between blood and urine catecholamine levels. Catecholamine levels showed no significant differences according to sex, age, or manner of death. Heart EP and heart EP/NE ratio were significantly higher in the group with CPR. Femoral DA, heart EP, heart NE, heart DA, and urine DA were significantly increased in the group with EP injection. Urine NE and urine DA showed significant differences among PMI groups, with both increased over PMI. In correlation analysis, femoral DA and urine NE displayed weak correlations with PMI. Regarding agony time, femoral and heart DA were significantly increased in long agony group compared to those in the short agony group. With regard to the cause of death, multiple comparison analysis for major categories (natural death, injury, intoxication, asphyxia, drowning, and fire death) revealed a significant increase of femoral NE in asphyxia in comparison with injury. In subgroup analysis for the group without EP injection, femoral NE (P = 0.048), femoral DA (P = 0.039), and heart EP (P = 0.021) showed significant differences between PMI groups. CONCLUSION: Results of this study have important implications for understanding postmortem catecholamine distribution and their mutual associations, influences of clinical and demographic factors, and relationships with agony time and cause of death in Korean population. Although comprehensive demonstration of catecholamine level as stress index was not possible in the present study, the assessment of postmortem catecholamine levels could be used as a supportive tool in classification of agonal status and differential diagnosis of the cause of death in particular cases. Further investigation is needed on this issue.

Sensing of Catecholamine in Human Urine Using a Simple Colorimetric Assay Based on Direct Melanochrome and Indolequinone Formation.

We used the first enzyme-free synthesis and stabilization of soluble melanochrome (MC) and 5,6-indolequinone (IQ) derived from levodopa (LD), dopamine (DA), and norepinephrine (NE) oxidation to develop a simple colorimetric assay for catecholamine detection in human urine, also elucidating the time-dependent formation and molecular weight of MC and IQ using UV-Vis spectroscopy and mass spectrometry. The quantitative detection of LD and DA was achieved in human urine using MC as a selective colorimetric reporter to demonstrate the potential assay applicability in a matrix of interest in therapeutic drug monitoring (TDM) and in clinical chemistry. The assay showed a linear dynamic range between 5.0 mg L-1 and 50.0 mg L-1, covering the concentration range of DA and LD found in urine samples from, e.g., Parkinson's patients undergoing LD-based pharmacological therapy. The data reproducibility in the real matrix was very good within this concentration range (RSDav% 3.7% and 6.1% for DA and LD, respectively), also showing very good analytical performances with the limits of detection of 3.69 ± 0.17 mg L-1 and 2.51 ± 0.08 mg L-1 for DA and LD, respectively, thus paving the way for the effective and non-invasive monitoring of dopamine and levodopa in urine from patients during TDM in Parkinson's disease.

Pathophysiology and Management of Glycemic Alterations before and after Surgery for Pheochromocytoma and Paraganglioma.

Glycemic alterations are frequent in patients with pheochromocytoma and paraganglioma (PPGL), but the real incidence of secondary diabetes mellitus (DM) is uncertain, because prospective multicenter studies on this topic are lacking in the literature. The main pathophysiological mechanisms of glucose homeostasis alterations in PPGL, related to catecholamine hypersecretion, are impaired insulin and glucagon-like peptide type 1 (GLP-1) secretion and increased insulin resistance. Moreover, it has been reported that different pathways leading to glucose intolerance may be related to the secretory phenotype of the chromaffin tumor. Predictive factors for the development of glucose intolerance in PPGL patients are a higher age at diagnosis, the need for a higher number of anti-hypertensive drugs, and the presence of secreting neoplasms. Tumor resection is strongly related to the resolution of DM in PPGL patients, with a significant improvement of glycemic control in most cases. We can hypothesize a different personalized therapeutic approach based on the secretory phenotype. The adrenergic phenotype is more closely related to reduced insulin secretion, so insulin therapy may be required. On the other hand, the noradrenergic phenotype mainly acts by increasing insulin resistance and, therefore, insulin-sensitizing antidiabetic agents can find a greater application. Regarding GLP-1 receptor agonists, the data suggest a possible promising therapeutic effect, based on the assumption that GLP-1 secretion is impaired in patients with PPGL. The principal predictors of remission of glycemic alterations after surgery for PPGL are a lower preoperative body mass index (BMI), a larger tumor, higher preoperative catecholamine levels, and a shorter duration of the disease (under three years). Otherwise, after resection of PPGL, hypoglycemia can occur as the result of an excessive rebound of preoperative hyperinsulinemia. It is a rare, but potentially severe complication reported in a lot of case reports and a few small retrospective studies. Higher 24-h urinary metanephrine levels, longer operative times and larger tumors are predictive factors for hypoglycemia in this setting. In conclusion, alterations of carbohydrate metabolism are clinically relevant manifestations of PPGL before and after surgery, but there is the need to conduct multicenter prospective studies to obtain an adequate sample size, and to allow the creation of shared strategies for the clinical management of these potentially severe manifestations of PPGL.

Clinical utility of urinary levels of catecholamines and their fraction ratios related to heart rate and thyroid function.

Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

Pheochromocytoma with Takotsubo Syndrome and acute heart failure: a case report.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor that can overproduce catecholamines. Heart failure and Takotsubo Syndrome (TTS) caused by excessive catecholamines are uncommon pheochromocytoma complications. CASE PRESENTATION: A 27-year-old woman was referred to our center for further preoperative assessment and adrenalectomy. She came to the emergency ward with the typical symptoms of acute coronary syndrome and heart failure, including chest stuffiness, dyspnea, epigastric pain, and diaphoresis. The high level of 24-hour urinary vanillylmandelic acid and abdominal computed tomography findings supported the diagnosis of pheochromocytoma. Transthoracic echocardiography showed diffuse hypokinesis of the left ventricular wall with an ejection fraction of 23%. All symptoms and left ventricular function recovered rapidly after left laparoscopic adrenalectomy. Histopathology findings confirmed the diagnosis of pheochromocytoma. Based on the above findings, we eventually diagnosed her with pheochromocytoma-induced TTS. CONCLUSIONS: This is a rare case of pheochromocytoma without hypertension complicated by TTS and acute heart failure. A diagnosis of pheochromocytoma-induced TTS should be considered for patients presenting with uncommon heart failure, even in patients without hypertension. Standard treatment is the surgical removal of the adrenal mass.

Pheochromocytoma: a retrospective study from a single center.

Objectives. Pheochromocytoma (PCC) is a neuroendocrine tumor derived from chromaffin tissue more frequently found in the adrenal medulla. Many discoveries over the last decade have significantly improved our understanding of PCC.Methods. We retrospectively reviewed all patients with a histological diagnosis of PCC at the Centro Hospitalar Universitario de Sao Joao, a tertiary and university hospital in Oporto, Portugal, between January 2009 and December 2017.Results. The study group included 33 patients. In most cases the diagnosis was suspected with more than half of patients presenting with hypertension and the third diagnosed during the work-up of an adrenal incidentaloma. About half of the patients was referred for genetic testing and 6 patients had a positive inherited susceptibility genetic pathogenic variant associated with classic cancer predisposition syndromes and also associated with newly described genes. In the incidentaloma group, genetic testing was performed in 3 (9%) patients with only 1 positive result. In the suspected group, 15 (45%) genetic tests were performed.Conclusions. In contrast to other studies, where only a minority of patients with PCC were referred for genetic counselling, in our study 54% of patients was referred for genetic testing. This study suggests that clinicians were correctly recognizing the need to refer young patients and patients with positive family history. However, opportunities for genetic testing are frequently missed due to low referral rates in patients with apparently sporadic PCC, particularly older than 30 years old. It is imperative that all the providers involved in the multidisciplinary care of patients with pheochromocytomas are aware of the genetic disorders associated with these unique tumors.

Tannic acid-directed synthesis of magnetic and boronic acid-functionalized metal-organic frameworks for selective extraction and quantification of catecholamines in human urine.

A novel magnetic borate-functionalized metal-organic framework nanocomposite was designed and fabricated for selective enrichment of catecholamines from human urine. Firstly, the polytannic acid (PTA) layer with natural low-cost and ecofriendly polyphenol tannic acid as the organic ligand and Fe3+ as the cross-linker was coated onto the surface of Fe3O4. Then, the borate-functionalized metal-organic framework (MIL-100(Fe)-B) with 5-boronobenzene-1,3-dicarboxylic acid as a ligand fragment was modified onto the PTA-coated Fe3O4 through a metal-ligand-fragment coassembly strategy. The obtained smart porous adsorbent Fe3O4@PTA@MIL-100(Fe)-B was confirmed by means of several characterization methods and then applied as an effective magnetic solid phase extraction (MSPE) sorbent for specific extraction of trace catecholamines in human urine. The Plackett-Burman design was used for screening the variables significantly affecting the extraction efficiency. Then, the significant factors were further investigated by the Box-Behnken design to determine the optimal extraction conditions. Under the optimal conditions, a method for selective MSPE combined with high-performance liquid chromatography with a fluorescence detector for the quantitation of catecholamines in human urine was developed and validated. With the proposed method, the linearity range was from 0.500 to 500 ng mL-1 for norepinephrine and epinephrine and from 1.00 to 500 ng mL-1 for dopamine. The detection limits were 0.050, 0.11, and 0.20 ng mL-1 for norepinephrine, epinephrine, and dopamine, respectively. The recoveries from spiking experiments varied from 91.5 to 108% with relative standard deviations (RSDs) of 0.80-4.8%. The established method is rapid, sensitive, accurate, inexpensive, and ecofriendly and was successfully applied to the determination of the target catecholamines in human urine samples.

Serial Hydrolysis for the Simultaneous Analysis of Catecholamines and Steroids in the Urine of Patients with Alopecia Areata.

Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography-tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4-122.9% and 88.8-123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4-21.5% and 2.0-21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.

A Case of Paraganglioma with Cyanotic Congenital Heart Disease.

Co-occurrence of cyanotic congenital heart disease (CCHD) and phaeochromocytoma (PCC) and paraganglioma (PGL) are rare, although some cases have been reported. We report a case of left paraganglioma in a 20-year-old lady with an underlying CCHD who underwent palliative Glenn shunt, subsequently developed polycythaemia and cavernous sinus thrombosis presented with palpitation, sweating, headache and hypertension of 3-months duration at the age of 17. The abdominal CT scan revealed an enhancing left paraaortic mass measuring 5.2 cm x 4.4 cm x 3.8 cm. A 24-hour urine catecholamine demonstrated raised noradrenaline level to six times upper limit of normal and hence diagnosis of left sympathetic (sPGL) was made. In view of the delayed diagnosis and significant morbidity associated with her condition, surgical treatment is no longer an option. Therefore, vigilant screening and early treatment of PCC-PGL in patients with CCHD are crucial in order to avoid significant morbidity and ensure a good quality of life.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine/Head and Neck Disease-Site Work Group. Part 1 of 2: Advances in Pathogenesis and Diagnosis of Pheochromocytoma and Paraganglioma.

This first part of a two-part review of pheochromocytoma and paragangliomas (PPGLs) addresses clinical presentation, diagnosis, management, treatment, and outcomes. In this first part, the epidemiology, prevalence, genetic etiology, clinical presentation, and biochemical and radiologic workup are discussed. In particular, recent advances in the genetics underlying PPGLs and the recommendation for genetic testing of all patients with PPGL are emphasized. Finally, the newer imaging methods for evaluating of PPGLs are discussed and highlighted.

Nanosized cation exchanger for the electrophoretic separation and preconcentration of catecholamines and amino acids.

The first example of application of nanosized polystyrene-based cation exchanger (NSCE) with sulfo groups as a dynamic coating of capillary walls was demonstrated. The conditions of dynamic coating formation were optimized and ensured the long-term stability of the coating. Capillary-to-capillary and day-to-day repeatabilities were 4% and 3%, correspondingly. The NSCE coating stability at various pH and influence of pH on the EOF mobility were investigated. The developed NSCE-modified coated capillaries provided improved resolution (Rs = 0.9-3.2 for catecholamines and Rs = 1.7-2.8 for amino acids) and efficiencies (330-520 ×103 t.p./m) of basic analytes, which are 1.5 times higher compared to untreated capillary. The optimized conditions were as follows: 50 mM phosphate buffer solution at pH 2.2 with 5 µM NSCE. The effect of the NSCE concentration in BGE on the electrophoretic mobilities of the analytes was investigated. The various online concentration techniques were tested in order to decrease the LODs. The simultaneous application of NSCE capillaries and field-amplified sample stacking provided the lowest LODs of catecholamines and amino acids and allowed to determine these analytes in human urine.

Experiences of Discrimination and Urinary Catecholamine Concentrations: Longitudinal Associations in a College Student Sample.

BACKGROUND: Experiences of discrimination are a risk factor for subsequent cardiovascular disease. However, there is a lack of longitudinal research examining associations between discrimination and urinary catecholamines. This is surprising given the likely mediating role of sympathetic nervous system dysregulation in the association between psychosocial stress and cardiovascular morbidity. PURPOSE: The current study examined the 3 year longitudinal association between experiences of discrimination and urinary catecholamines. METHODS: The sample included 149 college students (mean age at baseline = 18.8, standard deviation = 0.96; 45% Black/African American; 55% White/European American). Concentrations of epinephrine and norepinephrine-urinary catecholamines with established links to psychosocial stress exposure and subsequent morbidity-were determined from 12 hr overnight samples. RESULTS: Results indicated that experiences of discrimination were associated with increases in both epinephrine (ß = .284, standard error [SE] = .117, p = .015) and norepinephrine (ß = .306, SE = .114, p = .001). These longitudinal associations persisted after adjusting for negative affect, depression, and rejection sensitivity and did not vary as a function of race/ethnicity. CONCLUSIONS: Results suggest that examination of overnight urinary catecholamines as a biological mediator of associations between experiences of discrimination and cardiovascular morbidity is warranted.

Simple, rapid, and cost-effective microextraction by the packed sorbent method for quantifying of urinary free catecholamines and metanephrines using liquid chromatography-tandem mass spectrometry and its application in clinical analysis.

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors arising from adrenal and extra-adrenal chromaffin cells. They produce excessive amounts of catecholamines and their metabolites. A newly analytical procedure based on the semi-automated microextraction by packed sorbent (MEPS) technique, using a digitally controlled syringe (eVol) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed to quantify free urinary catecholamines and metanephrines. The important parameters affecting MEPS performance, namely the type of sorbent material (porous graphitized carbon (PGC), polar enhanced polymer (PEP), cation-exchange (CX) and C18), number of extraction cycles, and elution solvent system, were evaluated. The optimal experimental conditions involved the loading of sample mixture in seven extraction cycles through a C18 sorbent in a MEPS syringe, followed by using elution solutions (water/acetonitrile/formic acid, 95/4.75/0.25). The entire sample preparation took about 4 min. Chromatographic separation was well achieved with an HSS PFP column using the gradient elution. The linearity range of the method was 0.167-33.4 ng/mL for epinephrine, 0.650-130 ng/mL for norepinephrine, 1.53-306 ng/mL for dopamine, 1.34-268 ng/mL for metanephrine, 3.43-686 ng/mL for normetanephrine, and 1.33-265 ng/mL for 3-methoxytyramine. The intra- and interassay precisions were ≤ 12.8%, and the respective accuracies were 88.4-112.0% and 89.0-109.5%. The carryover and sample stability without acidification were also investigated. Validation using clinical urine specimens showed that the proposed method had higher sensitivity compared with other urinary biochemical tests. The developed MEPS-LC-MS/MS method was simple, fast, and cost-effective; it helped to obtain information about multiple metabolites. It is applicable in routine clinical laboratories for the screening of PPGL. Graphical abstract.

Unprecedented high catecholamine production causing hair pigmentation after urinary excretion in red deer.

Hormones have not been found in concentrations of orders of magnitude higher than nanograms per milliliter. Here, we report urine concentrations of a catecholamine (norepinephrine) ranging from 0.05 to 0.5 g/l, and concentrations of its metabolite DL-3,4-dihydroxyphenyl glycol (DOPEG) ranging from 1.0 to 44.5 g/l, in wild male red deer Cervus elaphus hispanicus after LC-MS analyses. The dark ventral patch of male red deer, a recently described sexually selected signal, contains high amounts of DOPEG (0.9-266.9 mg/l) stuck in the hairs, while DOPEG is not present in non-darkened hair. The formation of this dark patch is explained by the chemical structure of DOPEG, which is a catecholamine-derived o-diphenol susceptible to be oxidized by air and form allomelanins, nitrogen-free pigments similar to cutaneous melanins; by its high concentration in urine; and by the urine spraying behavior of red deer by which urine is spread through the ventral body area. Accordingly, the size of the dark ventral patch was positively correlated with the concentration of DOPEG in urine, which was in turn correlated with DOPEG absorbed in ventral hair. These findings represent catecholamine concentrations about one million higher than those previously reported for any hormone in an organism. This may have favored the evolution of the dark ventral patch of red deer by transferring information on the fighting capacity to rivals and mates. Physiological limits for hormone production in animals are thus considerably higher than previously thought. These results also unveil a novel mechanism of pigmentation based on the self-application of urine over the fur.

Label-free silver triangular nanoplates for spectrophotometric determination of catecholamines and their metabolites.

A novel method towards spectrophotometric determination of catecholamines and their metabolites differing in their functional groups has been developed. This method is based on a change in morphology of silver triangular nanoplates upon the action of cateсholamines and their metabolites, which is manifested by the decrease of the nanoparticle local surface plasmon resonance (LSPR) band intensity or its shift to the short-wavelength region of the spectrum. The shift value of the LSPR band or the change of its intensity increases with increasing concentration of catecholamines or their metabolites, which is proposed for their spectrophotometric determination. The limits of detection of catecholamines and their metabolites under selected conditions increase in the series homovanillic acid < vanillylmandelic acid < L-epinephrine < L-norepinephrine < dopamine and are 0.25, 1.2, 3.0, 64, and 130 µmol L-1, respectively. The selectivity of the proposed method was assessed using vanillylmandelic acid as example. It was found that the determination of vanillylmandelic acid does is not interfered in the presence of 4000-fold excess of Na+, K+, CH3COO-, and 1000-fold excess of Mg2+, Ca2+, Al3+, NO3-. The method also allows for the selective determination of vanillylmandelic acid in the presence of a 1000-fold excess of structurally related substances that do not contain either a catechol fragment or an electron donor substituent. The proposed approach was successfully applied to the determination of catecholamines in pharmaceuticals and artificial urine. Graphical abstract.

Boronic acid-modified polyhedral oligomeric silsesquioxanes on polydopamine-coated magnetized graphene oxide for selective and high-capacity extraction of the catecholamines epinephrine, dopamine and isoprenaline.

Amino-functionalized polyhedral oligomeric silsesquioxanes (POSS-8NH2) were covalently bound to the surface of polydopamine-coated magnetized graphene oxide. It was then reacted with 4-formylphenylboronic acid to prepare a "cubic boronic acid"-bonded magnetic graphene oxide adsorbent. The new adsorbent exhibits better selectivity and much higher adsorption capacity for ortho-phenols over adsorbents where small boronic ligands are directly bound to the surface of the material. It is shown to enable selective and faster enrichment of the catecholamines epinephrine (EP), dopamine (DA) and isoprenaline (IP) with high selectivity over many potential interferents that can occur in urine. The analytes were then quantified by HPLC with fluorometric detection. Under optimal conditions, response is linear (R2 ≥ 0.9907), limits of detection are low (0.54-2.3 ng·mL-1), and reproducibility is acceptable (inter- and intra-day assay RSDs of≤10.9%). The method was successfully applied to the determination of endogenous EP and DA and exogenous IP in urine samples. Graphical abstractSchematic of boronic acid (BA)-modified polyhedral oligomeric silsesquioxanes (POSS) on polydopamine-coated magnetized graphene oxide (magGO). The material (magGO@POSS-BA) has good selectivity and higher adsorption capacity to ortho-phenols and can be applied to enrich the catecholamines in urine.

Screening for phaeochromocytoma in patients with acute cerebrovascular disease: Is it necessary?

INTRODUCTION: Phaeochromocytoma may present with uncontrolled hypertension leading to haemorrhagic stroke (HS), ischaemic stroke (IS) and transient ischaemic attack (TIA). False elevation in the levels of CATS/ METS has been reported in acute cerebrovascular disease. Our aim was to analyse the frequency and pattern of elevations of CATS/METS in patients with acute cerebrovascular disease and to determine associated factors. MATERIALS AND METHODS: This is a retrospective study of 112 samples of CATS/ METS received by the laboratory over a two-year period, from patients with acute cerebrovascular disease. CATS/METS were measured using LC/MS/MS method. Clinical details and CATS/METS level were obtained from the database. Mann-Whitney U test and Kruskal Wallis test were used for statistical analysis. These statistical analyses were performed using SPSS v.20.0 (IBM Corp., Armonk, NY, USA). RESULTS: Of the 112 patients, 39% had HS, 54% had IS and 7% had TIA. A total of 29% of patients had elevated CATS/ METS. Elevated levels of CATS/METS were noted in 41% and 25% of HS and IS patients, respectively (p=0.53). Median norepinephrine, epinephrine and metanephrine levels in HS were significantly higher than IS (p< 0.05). Systolic blood pressure was higher in those who had elevated CATS/ METS (p=0.04). Only for two patients with elevated CATS/METS repeat testing was performed. Age, diastolic blood pressure and the time of sample collection in relation to the presentation, for CATS/METS were not significantly different between groups that had elevated levels of CATS/ METS versus those who did not. CONCLUSION: We noted that CATS/METS were elevated in one-third of patients, especially in patients with high systolic blood pressure. Increase in CATS/METS should be appropriately followed up with repeat testing. Since false elevation in CATS/METS has been reported in cerebrovascular disease, screening for phaeochromocytoma is best deferred for a month.

Adrenergic crisis as a debut form of a neuroblastoma. / Crisis adrenérgica como forma de debut de un neuroblastoma.

INTRODUCTION: The most common clinical presentation of neuroblastoma is an abdominal mass, but it can present with uncommon symptoms, such as adrenergic storm due to catecholamine release. OBJECTIVE: To describe an unusual presentation of neuroblastoma and the wide differential diagnosis that exists in an infant with adrenergic symptoms. CLINICAL CASE: A 7-week old female infant was evaluated due to a 3-week history of sweating and irritability associated with a 24-hour fever and respiratory distress. At admission, she presented poor general condition, irritability, sweating, facial redness, tachypnea and skin paleness, extreme sinus tachycardia, and high blood pressure (HBP), interpreted as adrenergic symptoms. The study was completed with abdominal ultrasound and magnetic reso nance imaging that showed a large retroperitoneal mass compatible with neuroblastoma. Plasma and urinary catecholamines tests showed high levels of dopamine, adrenaline, and noradrenaline, probably of tumor origin. We started antihypertensive treatment with alpha-blocker drugs, showing a good blood pressure control. The tumor was surgically resected without incidents and adequate subsequent recovery. The patient presented a favorable evolution after three years of follow-up. Con clusions: In an infant with adrenergic symptoms such as irritability, redness, sweating associated with HBP, it should be ruled out pathology heart or metabolic (hypoglycemia) pathology, intoxications, and/or adrenal pathology. Within this last one, neuroblastoma is the first diagnostic possibility, since it is one of the main tumors in childhood and, although this presentation is not usual, it can produce these symptoms.