Urinary Catecholamine Metabolites Research Articles

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.

Development and validation of a simple, fast and sensitive liquid chromatography-tandem mass spectrometry method to establish reference intervals for 24-h urinary free normetanephrine, metanephrine and methoxytyramine

ObjectiveTo develop and validate a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect urinary free metanephrines and methoxytyramine, establishing reference intervals. MethodsUrine samples were diluted with isotope internal standard solution, then analyzed directly using tandem mass spectrometry with multiple reaction monitoring measurement and electrospray ionization source in positive ion mode. Analytical parameters including linearity, lower limit of quantitation, imprecision and accuracy of the method were evaluated. The reference intervals for urinary catecholamine metabolites were established by analyzing 24-h urine samples collected from 81 apparently healthy volunteers. ResultsThe analytical times for MN, NMN, and 3-MT were at 2.79, 2.80, and 2.74 min, respectively. The method displayed excellent linearity (r > 0.99) in the range of 1-1000 ng/mL, with lower limits of quantification (LLOQ) at 0.50 ng/mL for MN and NMN, and 0.25 ng/mL for 3-MT. The method's intra-day and inter-day imprecisions were less than 8 %. The method recovery ranged from 96.8% to 105.8 % for MN, 89.7%–106.4 % for NMN, and 93.5%–106.2 % for 3-MT. No carry-over was observed during the analysis of all analytes. The LC-MS/MS method was used to establish reference intervals in 24-h urine samples from 81 apparently healthy volunteers. There was no association of sex with urinary free metabolites. ConclusionThis study established a novel, fast and sensitive LC-MS/MS method for determining urinary free catecholamine metabolites, which could facilitate screening and diagnosis for catecholamine-related tumors more conveniently and quickly.

Metyrosine-associated endocrinological changes in pheochromocytoma and paraganglioma.

Metyrosine (alpha-methyl-para-tyrosine) effectively reduces catecholamine levels in patients with pheochromocytoma/paraganglioma. However, improvements in physiological and metabolic parameters and changes in endocrine function associated with metyrosine administration should be validated in comparison to surgery. This study was performed to confirm the effects of metyrosine on the physiological, metabolic, and endocrinological functions of patients with pheochromocytoma/paraganglioma in the perioperative period. This retrospective cohort study was performed at a single university hospital. We included ten patients with pheochromocytoma/paraganglioma who received oral metyrosine after α-blocker therapy and consecutive surgeries. Urinary catecholamine metabolite levels and other clinical parameters were evaluated before and after metyrosine administration, and 1 week after surgery. The mean age was 53.1 ± 16.1 years. Of the ten participants (four men and six women), nine had pheochromocytoma and one had paraganglioma. The median maximum metyrosine dose was 750 mg/day. Urinary catecholamine metabolite levels significantly decreased in a dose-dependent manner after metyrosine administration. Both systolic and diastolic blood pressure significantly decreased after metyrosine and surgical treatment. Metyrosine administration significantly improved insulin sensitivity, although surgery improved the the basal insulin secretion. Additionally, serum prolactin and thyroid-stimulatory hormone levels were significantly increased by metyrosine treatment, whereas plasma renin activity was decreased. Metyrosine significantly reduced catecholamines in patients with pheochromocytoma/paraganglioma and ensured the safety of the surgery. Adjustment of metyrosine administration may make surgical pretreatment more effective in achieving stabilized blood pressure and improving glucose metabolism. Endocrine parameters may manifest as the systemic effects of metyrosine administration.

Optimising urinary catecholamine metabolite diagnostics for neuroblastoma.

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. 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). 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. 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.

A false positive 68Ga-DOTA-TATE involvement in an adrenal mass: Kaposi Sarcoma

Abstract Introduction Pheochromocytomas (PCC) are rare tumors (0.8/100000) arising from adrenal medulla cells. The most common symptom of PCC is persistent high blood pressure. Apart from symptomatic cases, PCCs can also be asymptomatic and can be detected incidentally. Surgical treatment is urgent if catecholamine hypersecretion is detected. After the detection of hormonal hyperfunction in patients with PCC, the diagnosis is confirmed by anatomical and functional imaging. As we all know, there is no possibility of histopathological diagnosis before surgery in PCC. Therefore, rare coexistence of false positive Ga68-DOTA-TATE uptake and falsely high urinary catecholamine metabolite levels may lead to adrenalectomy of the patients without PCC. Here we describe a patient who underwent adrenalectomy with a prediagnosis of PCC but received a different pathological diagnosis. Clinical Case A 50-year-old male patient who was diagnosed with AIDS after being investigated for fever of unknown origin was referred to the endocrinology department because of a mass in the left adrenal gland. The patient had complaints of headache, palpitation and sweating. On physical examination, there was a red nodular lesion on his face and a palpable lymph node in the inguinal region. His blood pressure was 160/100 mm-Hg, pulse was 100/min and body temperature were 37.1°C. Ambulatory blood pressure measurements showed that the patient's blood pressure was constantly high. Non-contrast CT showed a tumor of 20×15 mm in size (Hounsfield Unit:38) in the left adrenal gland (Fig-1). In terms of hormonal hyperfunction, no cortisol or aldosterone hypersecretion was detected, but urine normetanephrine was found to be 4 times higher than the upper normal limit (Table 1). Functional imaging revealed pathologically increased Ga68-DOTA-TATE uptake in the left adrenal mass and multiple lymph nodes (SUVmax 5.9 and 3.2) (Fig-1). The pathology of the patient who underwent simultaneous inguinal lymph node excision and adrenalectomy was reported as Kaposi sarcoma (KS). The patient is currently receiving treatment for AIDS and KS. Conclusion KS is a type of cancer that occurs especially in immunocompromised patients. Although there have been publications in the last decade suggesting that 18F-FDG-PET/CT imaging may be beneficial in KS, there are no articles recommending the use of Ga68-DOTA-TATE. Upregulation of neuroendocrine genes has also been shown in publications investigating KS, which is thought to originate from endothelial cells. This may explain why there is Ga68-DOTA-TATE involvement in these lesions. Pheochromocytoma is referred to as “the great mimicker” in the articles of radiology and its similarity with all types of adrenal lesions causes PCC to not be excluded by anatomical imaging. We wanted to share these two diseases, which are very unlikely to come together and cause confusion, and explain the factors that can lead to this confusion.

Adrenal Hemorrhage Versus Neuroblastoma in Newborn with Right Suprarenal Mass and Hypertension: A Case Report

Adrenal hemorrhage is a potentially life-threatening condition that rarely presents in the neonatal period. The large size and increased vascularity of the average infant adrenal gland increase the tendency of bleeding. Predisposing factors may include macrosomia, birth asphyxia, perinatal injuries, septicemia, and coagulopathy. It can also occur without obvious risk factors. The most common presenting findings are poor feeding, vomiting, persistent jaundice, anemia, and abdominal mass. However, the event may be asymptomatic and be detected incidentally. Ultrasound imaging is the cornerstone of diagnosis and follow-up monitoring. Herein, we report an unusual case of a male newborn with an adrenal hemorrhage associated with hypertension. The lesion was detected by ultrasound as an echogenic cystic mass at the right suprarenal area. The mass was initially mimicking neuroblastoma. Nevertheless, the normal levels of urine catecholamine metabolites and the regression of the mass size verified the diagnosis. The infant was successfully managed conservatively, and the mass completely resolved without calcification or adrenal insufficiency.

Detection of catecholamine metabolites in urine based on ultra-high-performance liquid chromatography-tandem mass spectrometry.

The excretion of neurotransmitter metabolites in normal individuals is of great significance for health monitoring. A rapid quantitative method was developed with ultra-performance liquid chromatography-tandem mass spectrometry. The method was further applied to determine catecholamine metabolites vanilymandelic acid (VMA), methoxy hydroxyphenyl glycol (MHPG), dihydroxy-phenyl acetic acid (DOPAC), and homovanillic acid (HVA) in the urine. The urine was collected from six healthy volunteers (20-22 years old) for 10 consecutive days. It was precolumn derivatized with dansyl chloride. Subsequently, the sample was analyzed using triple quadrupole mass spectrometry with an electrospray ion in positive and multireaction monitoring modes. The method was sensitive and repeatable with the recoveries 92.7-104.30%, limits of detection (LODs) 0.01-0.05 μg/mL, and coefficients no less than 0.9938. The excretion content of four target compounds in random urine samples was 0.20 ± 0.086 μg/mL (MHPG), 1.27 ± 1.24 μg/mL (VMA), 3.29 ± 1.36 μg/mL (HVA), and 1.13 ± 1.07 μg/mL (DOPAC). In the urine, the content of VMA, the metabolite of norepinephrine and adrenaline, was more than MHPG, and the content of HVA, the metabolite of dopamine, was more than DOPAC. This paper detected the levels of catecholamine metabolites and summarized the characteristics of excretion using random urine samples, which could provide valuable information for clinical practice.

Clinical Outcome of Carotid Body Paraganglioma Management: A Review of 10-Year Experience.

Background Carotid body paragangliomas are rare neoplasms usually benign, however sometimes presenting as highly aggressive tumors. Surgery is the main line of treatment. Purpose To study and describe clinical presentations, surgical approaches, postoperative complications, and treatment outcomes. Materials and Methods A single-institution retrospective analysis of 19 cases with carotid body paragangliomas who were candidates for surgery from January 2009 through January 2019 with a mean follow-up period of 58.8 months. Results The mean age was 46 years with the female predominance of 63%. The mean size of the tumor was 4.3 cm. All cases were presented with a painless pulsating neck lump located anteriorly at the level of the hyoid bone. Neck US was done in all cases as a primary screening investigation. CT scanning was the second main investigation performed in 17 cases (89.5%) revealing tumors attached to the carotid artery at its bifurcation. Urinary catecholamine metabolites were measured in all cases to rule out familial functioning types. 5 cases (26.3%) were malignant. All cases were surgically approached through transcervical transverse incision. 11, 5, and 3 cases were classified as Shamblin's type II, III, and I, respectively. All tumors were R0 resected with nodal neck dissection conducted in the malignant group. Major complications occurred in 4 cases (21%) during tumor dissection from the adventitia of carotid bifurcation. ECA ligation was performed in one case (5.3%). 2 patients (10.5%) suffered XII nerve paralysis. Carotid artery blowout occurred in one patient (5.3%) and was immediately controlled. No operative mortality occurred. All patients were free of disease during the follow-up period. 4 malignant cases (21%) suffered a systemic relapse to bone and lung metastasis justifying adjuvant chemotherapy, radiotherapy, or both. Conclusions Surgery is the treatment of choice for carotid body paragangliomas. Complete R0 resection should be justified especially in case of malignancy. Adjuvant chemotherapy or radiotherapy is an option for patients with primary malignancy or relapse.

Stability and reference intervals of spot urinary fractionated metanephrines and methoxytyramine by tandem mass spectrometry as a screening method for pheochromocytoma and paraganglioma.

The 24 h urinary-fractionated metanephrine (MN) and normetanephrine (NMN) are recommended as the preferred indicators for laboratory diagnosis of pheochromocytoma and paraganglioma (PPGL). However, it might cause missed diagnosis for some type of PPGL, in addition, 24-h urine collection is inconvenient and prone to error, so we aimed to develop a better screening method. Urine samples from patients of primary hypertension (n = 317) or PPGL (n = 64) were collected randomly and in a 24-h cycle. Samples were prepared by solid phase extraction (SPE) and analyzed with LC-MS/MS. Sample stability under different storage conditions was investigated. The gender-specific reference intervals of spot urinary catecholamine metabolites adjusted by creatinine were established and the diagnostic performance was evaluated. Urinary MN, NMN (MNs), and 3-methoxytyramine (3-MT) were stable at room temperature or 4 °C for at least 4 days without adding any preservatives and at -20 °C for at least 11 weeks. Reference intervals of spot urinary MN, NMN and 3-MT adjusted by creatinine were 20.2-174.0, 47.6-452.0, and 20.6-398.5 µg/g for male and were 15.3-202.0, 34.4-461.0, and 38.0-392.6 µg/g for female. The sensitivity and specificity of spot urinary MN, NMN, and 3-MT were similar with that of 24-h urine (P > 0.05). Regardless of urine sample type, combined application of MNs or MNs and 3-MT can improve the diagnosis efficiency of MN and 3-MT alone. Adding 3-MT to diagnosis model can improve diagnostic sensitivity to some extent, and the analysis of spot urinary MNs and 3-MT can provide reliable diagnostic information in a much shorter diagnostic time, it may reduce the medical expenses indirectly.

Ganglioneuroma, una entidad a considerar en las masas adrenales incidentales. Revisión de la literatura y reporte del primer caso de extracción completamente laparoscópica en México


 
 
 
 RESUMENINTRODUCCIÓNLos ganglioneuromas son tumores muy poco frecuentes, de comportamiento benigno, que derivan de la cresta neural. Su diagnóstico es generalmente incidental y de presentación clínica silente. Se localizan con mayor frecuencia en el retroperitoneo y mediastino, rara vez presentandose en la glándula suprarrenal (1/1 000 000 en la población general).
 REPORTE DE CASO Masculino de 56 años de edad, asintomático, quien es referido a valoración por hematuria microscópica. Al realizar Tomografía contrastada se encuentra tumoración suprarrenal izquierda de 4 cm, homogénea, con atenuación <20 UH a la administración de contraste intravenoso y lavado tumoral negativo. Los metabolitos de catecolaminas séricas y urinarias fueron normales. Se realizó adrenalectomía izquierda laparoscópica. El estudio histopatológico reporta proliferación de células fusiformes a nivel de la médula adrenal, células ganglionares maduras, que corresponde ganglioneuroma suprarrenal.
 DISCUSIÓNDebido a su presentación clínica silente, el ganglioneuroma suprarrenal representa un reto diagnóstico. El hallazgo en tomografía de una masa suprarrenal metabólicamente no funcionante, con atenuación en la fase simple < 40 UH, y presencia de calcificaciones puntiformes hace sospechar ganglioneuroma, sin embargo ya que comparte características predictoras de malignidad como es el caso de diámetro >4 cm y retardo en el lavado tumoral, el tratamiento terapéutico y diagnóstico más adecuado, es la adrenalectomía laparoscópica.
 
 
 

Catecholamine excretion profiles identify clinical subgroups of neuroblastoma patients

IntroductionAnalysis of urinary catecholamine metabolites is one of the primary modalities to diagnose patients with neuroblastoma. Although catecholamine excretion patterns have been recognised in the past, their biological rationale and clinical relevance remain largely unknown. Therefore, this study was designed to identify unique catecholamine excretion patterns and elucidate their underlying biology and clinical relevance. Patients and methodsA panel of 25 neuroblastoma cell lines was screened for catecholamine excretion. Detection of the catecholamine enzymes was performed using Western blot. Based on catecholamine enzymes presence and excreted catecholamine metabolites, excretion profiles were defined. The prevalence of these profiles was investigated in vivo using diagnostic urines from 301 patients with neuroblastoma and immunohistochemistry on primary tumours. The clinical relevance of the profiles was determined by linking the profiles to clinical characteristics and outcome of patients with neuroblastoma. ResultsFour excretion profiles (A-D) were identified in vitro, which correlated with the relative protein expression of the catecholamine enzymes. These profiles were also identified in urine samples from patients with neuroblastoma and correlated with the presence of the catecholamine enzymes in the tumour. Strikingly, in 66% of the patients, homovanillic acid and vanillylmandelic acid excretions were discordant with the catecholamine profiles. Clinical characteristics and outcome gradually improved from patients with profile A (predominantly high risk) towards profile D (predominantly observation), with 5-years overall survival of 35% and 93%, respectively. ConclusionsCatecholamine profiles in vitro and in vivo reflect, to a large extent, the presence of the individual catecholamine enzymes and represent distinct subgroups of patients with neuroblastoma.

Pheochromocytoma presenting with severe hyperglycemia and metabolic acidosis following intra-articular glucocorticoid administration: a case report

BackgroundThere are several reports of pheochromocytoma crisis triggered by systemic glucocorticoid administration. However, pheochromocytoma crisis after intra-articular glucocorticoid administration has been rarely reported.Case presentationA 45-year-old Japanese man presented to our hospital with a sudden, severe headache. He had no history of diabetes. He had received an intra-articular injection of betamethasone (2 mg) for joint pain, 2 days prior to his admission. On examination, his blood pressure was 240/126 mmHg and pulse was 120 beats/minute. The possibility of cerebrovascular events was ruled out by imaging studies and lumbar puncture. Blood tests revealed severe hyperglycemia (523 mg/dL) and metabolic acidosis (pH 7.21, anion gap 26.2 mEq/L, lactate 11.75 mmol/L) with a glycosylated hemoglobin level of 5.7%. Although a urine sample could not be obtained, fulminant type 1 diabetes mellitus and diabetic ketoacidosis were suspected based on these findings. However, after the initial treatment for diabetic ketoacidosis, his insulin secretion was found to be normal and the plasma levels of ketones were not elevated. This excluded the possibility of fulminant type 1 diabetes mellitus and diabetic ketoacidosis. Subsequently, a left adrenal gland tumor and elevated levels of serum catecholamine and urinary catecholamine metabolites were detected, while his other hormone levels were normal. Serum catecholamine levels did not decrease following the clonidine test, and a functional scintigraphy using iodine-131 metaiodobenzylguanidine showed strong uptake in the region of the left adrenal gland. Although no signs of pheochromocytoma crisis, such as paroxysmal hyperglycemia and hypertension, had been observed since admission, a pheochromocytoma was diagnosed based on the investigations. After controlling his blood pressure, a left adrenalectomy was performed.ConclusionsThis case illustrates that intra-articular glucocorticoid administration can induce a pheochromocytoma crisis and an increase in hyperglycemia, and that pheochromocytoma crisis can resemble the clinical picture of fulminant type 1 diabetes mellitus owing to severe hyperglycemia with metabolic acidosis and normal glycosylated hemoglobin levels, especially under the influence of glucocorticoid.

Antidopaminergic medication in healthy subjects provokes subjective and objective mental impairments tightly correlated with perturbation of biogenic monoamine metabolism and prolactin secretion.

ObjectivesOff-label prescription of antipsychotics to patients without psychotic symptoms has become a routine matter for many psychiatrists and also some general practitioners. Nonetheless, little is known about the possibly detrimental effects of antidopaminergic medications on general psychopathology, subjective mental state, or a possible association with physiological parameters in nonpsychotic individuals.MethodsIn this randomized, single-blinded study, groups of healthy volunteers (n=18) received low doses of reserpine, aripiprazole, haloperidol, or placebo on 7 successive days. Relevant physiological parameters (plasma prolactin, concentrations of catecholamine metabolites in plasma, and 24-hour urine) and each subject’s mental state (Positive and Negative Syndrome Scale, Hamilton Rating Scale for Depression, visual analogue scale, Beck Depression Inventory II) were assessed at the start and end of the trial.ResultsOf the three active treatments, only reserpine caused a significant increase in some plasma- and urine-catecholamine metabolites, but all three medications evoked objective and subjective changes in general psychopathology scores, which correlated with individual increases in plasma homovanillic acid concentrations. Both objective and subjective impairments were significantly more pronounced in the subgroup with greatest increase of plasma prolactin. Subjects experiencing the most pronounced side effects under haloperidol, which compelled them to drop out, showed significantly higher prolactin concentration increases than those who tolerated haloperidol well.ConclusionWe found consistent associations between altered markers of dopamine transmission and several objective and subjective mental impairments in healthy volunteers after 1 week’s treatment with antidopaminergic medications. These findings should draw attention to a more intensive risk–benefit evaluation in cases of off-label prescription of antipsychotic medications.

Random urine testing for carcinoid tumours in paediatric subjects using a LC-MSMS method with age specific normalised reference intervals

Introduction: In clinical practice, tests for urine catecholamine metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) is often used for diagnosis of carcinoid tumours of the stomach, colon and lung.1,2 Paediatric reference intervals have been traditionally based on timed urine collections. However, there is difficulty in collecting timed urine samples in infants and children.

3-Methoxytyramine: An independent prognostic biomarker that associates with high-risk disease and poor clinical outcome in neuroblastoma patients

IntroductionPrognosis of neuroblastoma patients is very diverse, indicating the need for more accurate prognostic parameters. The excretion of catecholamine metabolites by most neuroblastomas is used for diagnostic purposes, but their correlation with prognosis has hardly been investigated. Therefore, we performed an in-depth analysis of a panel of elevated urinary catecholamine metabolites at diagnosis and their correlation with prognosis. Patients and methodsRetrospective study of eight urinary catecholamine metabolites in a test (n = 96) and validation (n = 205) cohort of patients with neuroblastoma (all stages) at diagnosis. ResultsMultivariate analyses, including risk factors such as stage and MYCN amplification, revealed that 3-methoxytyramine (3MT) was an independent risk factor for event-free survival (EFS) and overall survival (OS). Furthermore, only 3MT appeared to be an independent risk factor for both EFS and OS in high-risk patients, which was independent of modern high-risk therapy and immunotherapy. Among high-risk patients, those with elevated 3MT and older than 18 months had an extremely poor prognosis compared to patients with non-elevated 3MT and younger than 18 months (5-year EFS of 14.3% ± 4% and 66.7% ± 18%, respectively, p = 0.001; 5-year OS of 21.8% ± 5% and 87.5% ± 12%, respectively, p < 0.001). ConclusionsElevated 3MT at diagnosis was associated with high-risk disease and poor prognosis. For high-risk patients, elevated 3MT at diagnosis was the only significant risk factor for EFS and OS. 3MT was also able to identify subgroups of high-risk patients with favourable and extremely poor prognosis.

A multi-walled carbon nanotubes/cellulose acetate composite electrode (MWCNT/CA) as sensing probe for the amperometric determination of some catecholamines

Abstract A morphological and electroanalytical characterization of a glassy carbon electrode modified with multi-walled carbon nanotubes dispersed into cellulose acetate polymer matrix (GC/MWCNT/CA), was reported. The morphology of the modified electrode reveals a favorable distribution of the carbonaceous fibers interconnected within the cellulose acetate matrix, showing an improved active surface area. The electrode was tested as an sensing probe for the detection of some important catecholamines such as dopamine and epinephrine using cyclic volatmmetry and differential pulse voltammetry (DPV) in 50 mM H3PO4. Under DPV conditions, the detection limits of the investigated catecholamines are comprised between 1 μM and 10 μM. A reverse phase chromatographic technique (pH 3.5), coupled with the GC/MWCNT/CA amperometric sensor was optimized for the separation and quantification of the tested catecholamines. Under the optimized conditions, the investigated analytes, including an important urinary catecholamine metabolite such as the vanillylmandelic acid, were eluted and separated in about 10 min with good chromatographic efficiency and resolution. The effects of various common interferents on the analytical signal, were also evaluated. A solid phase extraction pre-concentration procedure accomplished with chromatography and electrochemical detection allows the possibility to lower the detection limits of the investigated molecules at level of 1–5 nM. Real samples of pharmaceutical vials and urine samples were successful analyzed using the proposed amperometric sensor in two different analytical contexts: DPV and amperometry after solid phase extraction procedure coupled with liquid chromatography.

From benign adrenal incidentaloma to adrenocortical carcinoma: an exceptional random event

New European guidelines for the management of adrenal incidentalomas were recently released. One of the most novel recommendations is to stop following patients when they present a typical, small and non-secreting adenoma. We report here the case of a 71-year-old man with such an adenoma, who developed an adrenocortical carcinoma (ACC) fourteen years later, with subsequent metastases and death. Clinically, he had a normal blood pressure and no sign of hormonal hypersecretion. The hormonal work-up showed no hormone excess: urinary free cortisol level was normal, the diurnal cortisol rhythm was respected and urinary catecholamine metabolites levels were normal. Computed tomography (CT) scan showed a homogeneous lesion, with a low density. The lesion remained unchanged during the five years of follow-up. Eight years after the last CT, a large right heterogeneous adrenal mass was incidentally discovered during an ultrasound examination. On CT scan, it was a 6 cm heterogeneous tumor. On hormonal work-up, there was no secretion. The patient was operated of an adrenalectomy, and the histology described an ACC with a Weiss score at 8, with no benign contingent. To our knowledge, this is the first case of an ACC occurring in a patient with prior adrenal imaging showing a typical benign adenoma.

Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients

IntroductionNeuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. Patients and methodsRetrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients. ResultsElevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel. ConclusionsOur study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients.

神経芽細胞腫のカテコラミン代謝に関する研究 : 尿中 C. A. 代謝産物分離定量法による検討

神経芽細胞腫のカテコラミン代謝に関する研究 : 尿中 C. A. 代謝産物分離定量法による検討

Simultaneous visual sustained attention-discrimination and goal-directed search are associated with excretion of catecholaminergic metabolites in children with attention-deficit/hyperactivity disorder

The relationship between visual sustained attention-discrimination and goal-directed search was evaluated using a visual discrimination and exploration (goal-directed search) paradigm and urinary excretion of catecholaminergic metabolites [dopamine (DA) and norepinephrine (NE)] in 6–12 year-old children ( n = 31) strictly selected and diagnosed with attention-deficit/hyperactivity disorder (ADHD) using diagnostic criteria and other objective indices. The Structured Clinical Interview (SCID) (DSM-IV) was used to formally diagnose ADHD in children. A cognitive laboratory test was used to assess visual sustained attention-discrimination and goal-directed search (Children Color Trails Test 1 and 2). Urinary excretion of DA and NE metabolites was measured via reversed high-pressure liquid chromatography (HPLC). Pearson product-moment correlations were used to investigate the relationship between visual sustained attention and goal-directed search and urinary catecholamine metabolites of DA and NE. The present findings revealed a positive and moderately significant relationship between visual sustained attention and visual exploration and catecholaminergic metabolite levels of NE and DA, according to expectation. Decreased visual sustained attention and goal-directed search was associated with decreased DA and NE metabolite levels. The present results are consistent with past research with children with ADHD and studies with primates examining the intricate and respective interaction between the Locus Coeruleus and visual sustained attention-discrimination and the Ventral Tegmental Area and goal-directed search (visual exploration) respectively modulated through NE and DA. Applied and theoretical issues associated with the present findings also are discussed addressing recent computer-generated analogues of action selection models within the context of the extant findings.