Urinary Catecholamines Research Articles

High specificity and sensitivity of spot urine normetanephrine-to-creatinine ratios in the diagnosis of canine pheochromocytoma.

To evaluate the specificity/sensitivity and predictive values of urine spot metanephrines-to-creatinine ratios to diagnose canine pheochromocytomas and to determine whether there is a correlation between urine catecholamine levels and tumor volume. In a retrospective study, 32 client-owned dogs with adrenal tumors were identified (13 nonpheochromocytoma and 19 pheochromocytoma). Medical records were evaluated for patients undergoing adrenalectomy between August 2020 and August 2023. Patients were divided into groupings of pheochromocytoma and other adrenal tumor diagnosis on the basis of histopathology. Urine spot normetanephrine concentrations were significantly elevated in dogs with pheochromocytomas compared to dogs with other adrenal tumors. Sensitivity was 78.9%, specificity 76.9%, positive predictive value 83.3%, and negative predictive value 71.4% for discriminating between pheochromocytoma and nonpheochromocytoma. Spot urine metanephrine concentrations were not significantly different between the 2 groups. Only 5 of 19 pheochromocytoma patients had urine normetanephrine concentrations > 4 times the upper reference limit, which is the previously established diagnostic cutoff. Median tumor volume did not correlate with normetanephrine values, nor did those values correlate to patients that experienced intraoperative complications. Twenty-one percent of cases were biochemically silent pheochromocytomas. Urine normetanephrine-to-creatinine levels but not metanephrine-to-creatinine levels can potentially differentiate a pheochromocytoma from a nonpheochromocytoma. Previously published guidelines of 4 times the upper reference limit in spot urine metanephrines testing used to diagnose pheochromocytomas will lead to a significant number of missed diagnoses.

Sympathetic activity markers in patients with resistant hypertension with renal dysfunction

Aim. To study the informativeness of sympathetic activity markers and perirenal adipose tissue (PRAT) in assessing renal function decline in patients with resistant hypertension (RH).Material and methods. The study included 63 patients with RH of both sexes aged 40-80 years. The main group included 19 patients with chronic kidney disease (CKD). The control group consisted of 44 patients with RH without CKD. All patients were assessed for uric acid, blood lipid profile, beta-adrenergic reactivity of erythrocyte mem­branes, free metanephrine and normetanephrine in plasma and 24-hour urine. The renal function was assessed by the glomerular filtra­tion rate calculated using the CKD-EPI equation. Twenty-four hour blood pressure monitoring was performed on the brachial artery of one arm at intervals of 15 minutes during the day and 30 minutes at night. Kidney size and PRAT were calculated based on the magnetic reso­nance imaging.Results. In both groups of patients, a significant increase in blood normetanephrine and beta-adrenergic reactivity of erythrocyte mem­branes relative to the reference values was shown. Blood and 24-hour urine metanephrine were within the reference intervals. No differences were found between the sympathetic activity indices in the main and control groups. In the main group patients, the PRAT thickness was greater (p=0,013), and the kidney diameter was smaller (p=0,046) than in the control group patients.Conclusion. CKD in RH patients is not accompanied by additional significant changes in sympathetic regulation, assessed by the blood and 24-hour urine catecholamine levels, the degree of beta-adrenergic receptor desensitization and variability of blood pressure. PRAT increase according to magnetic resonance imaging in patients with RH is associated with a decrease in renal filtration function.

Energy Expenditure in Critically Ill Patients with Aneurysmal Subarachnoid Hemorrhage, Intracerebral Hemorrhage, and Traumatic Brain Injury-A Prospective Observational Study.

Energy expenditure (EE) in patients with aneurysmal subarachnoid hemorrhage (SAH) may differ from other intracranial pathologies, such as intracerebral hemorrhage (ICH) or traumatic brain injury (TBI), due to an activation of the sympathetic nervous system. Indirect calorimetry (IC) is recommended, but is not always available. We study EE, catabolism, and metabolic stress in patients with SAH, TBI, ICH, and sepsis as controls. A prospective observational study was conducted in the intensive care units of the University Medical Center Hamburg-Eppendorf, Germany. IC was used to measure EE on days 2-3, 5-7, and 10-15 post-admission. Urinary catecholamines, metabolites, and urine urea were also measured. Statistical analysis included t-tests, Chi-square tests, and generalized mixed models. We included 110 patients-43 SAH patients (13 with the surgical securing of the aneurysm and 30 with coil embolization of the aneurysm), 22 TBI patients, 23 ICH patients, and 22 controls. The generalized linear mixed model analysis for groups and timepoints including age, height, and weight as covariates revealed a significantly lower EE at timepoint 1 for ICH versus SAH-interventional (p = 0.003) and versus the control (p = 0.004), as well as at timepoint 2 for ICH versus SAH-interventional (p = 0.002) and versus SAH-surgical (p = 0.013) with a lower EE in ICH patients. No significant differences between groups were found for EE at the other timepoints, or concerning urine urea and measurements of catecholamines in urine. In patients with SAH, ICH, and TBI, no meaningful differences in EE were detected compared to septic critically ill patients, except for a lower EE in ICH patients in the early phase.

7204 An Unexpected Cause of Ga-68 Dotatate PET/CT Somatostatin Receptor Avidity in a Pediatric Patient with Hereditary Paraganglioma-Pheochromocytoma Syndrome due to an SDHA Mutation

Abstract Disclosure: K. Leopold: None. S. Polites: None. L. Binkovitz: None. L. Casas: None. A.N. Lteif: None. Title: An Unexpected Cause of Ga-68 Dotatate PET/CT Somatostatin Receptor Avidity in a Pediatric Patient with Hereditary Paraganglioma-Pheochromocytoma Syndrome due to an SDHA Mutation. Introduction: Individuals with Succinate Dehydrogenase (SDHx) gene mutations have an increased risk of paragangliomas and pheochromocytomas beginning in childhood.Clinical Case: A 9 year old male with Cornelia de Lange syndrome and a paternally inherited SDHA pathogenic gene variant (c1534C>T) presented with worsening migraine headaches and skin pallor with activity. 24 hour urine fractionated metanephrines were mildly elevated, with metanephrine 122 mcg/24h (29-92 mcg/24 h), normetanephrine 187 mcg/24 h (34-169 mcg/24 h), and total metanephrine 309 mcg/24 h (47-223 mcg/24 h). Ga-68 DOTATATE PET/CT showed a focus of moderately increased radiotracer activity in the anterior aspect of the distal gastric antrum with a max SUV 8.2 corresponding to a 9x7 mm nodule on CT in the same area, suggestive of underlying somatostatin receptor positive lesion such as a paraganglioma. MRI with contrast completed to further characterize the lesion showed no visible mass corresponding to the focal area of radiotracer uptake on DOTATATE PET/CT. Repeat 24 h urine metanephrines continued to show mild elevation of metanephrine (138 mcg/24h), normetanephrine (200 mcg/24h), and total metanephrines (338 mcg/24h). 24 hour urine catecholamines, 5-Hydroxyindoleacetic acid, and homovanillic acid were normal. An upper endoscopic ultrasound was completed which confirmed the presence of a lesion near the stomach but not arising from the stomach wall and not consistent with a gastrointestinal stromal tumor. CT enterography with IV contrast showed a 6x6 mm enhancing mass within the distal right lateral gastric wall. Due to ongoing symptoms, mild elevations in urine fractionated metanephrines, and a clear mass on US and CT, the patient underwent laparoscopic abdominal exploration where a 14x14x13 mm mass with surrounding gastric and duodenal serosa was excised with primary closure of the bowel. Pathology showed ectopic pancreatic tissue in the wall of the small bowel and stomach. Repeat Ga-68 DOTATATE PET/CT 5 months following surgery showed resolution of the distal gastric somatostatin receptor avidity. Clinical Lesson: This is the first case of ectopic pancreatic tissue mimicking a paraganglioma in a pediatric patient with hereditary paraganglioma-pheochromocytoma syndrome. False positive imaging should be considered in patients with SDHx mutations when the uptake is atypical in location and when the elevation in urine metanephrines is mild. Presentation: 6/3/2024

Enhanced detection of catecholamines in human urine using Cis-diol-microporous organic networks with PT-SPE and HPLC-MS/MS

A novel cis-diol-microporous organic networks (MONs-2OH) material was synthesized via room temperature and Sonogashira coupling reactions, which exhibits exceptional adsorption properties for catecholamines (CAs). MONs-2OH demonstrates robust hydrogen bonding and π-π stacking interactions, crucial for effective adsorption. The MONs-2OH was incorporated into pipette tip solid-phase extraction and developed a new method for detecting CAs in human urine using HPLC-MS/MS. Characterization of the adsorbent revealed its high stability, large specific surface area, abundant phenolic hydroxyl groups, rapid extraction speed, and superior adsorption efficiency. The method achieved a wide linear range (0.5–500 ng/mL), low detection limits (0.06–0.26 ng/mL), high accuracy (90.4 %-99.4 %), and excellent precision (RSD ≤ 10 %). Comparative studies showed MONs-2OH outperforms commercial adsorbents in terms of recovery and adsorption capacity. The results underscore the potential of MONs-2OH for rapid and sensitive CAs determination, offering significant advantages for the auxiliary diagnosis of depression and enhancing the application of PT-SPE in sample pretreatment.

Retroperitoneal Functional Paraganglioma: A Case Report and Review of the Literature

Retroperitoneal paragangliomas are rare neuroendocrine tumors. They are defined as extra-adrenal chromaffin tumors and account for around 1/5th of all chromaffin tumors. They are often asymptomatic and can reach significant dimensions. We report the case of a 52-year-old female patient who presented with abdominal pain. Thoraco-abdomino-pelvic computed tomography (TAP CT) showed a right retroperitoneal tumor, urinary methoxylates were elevated. After adequate pharmacological preparation, the patient underwent surgery without complications. Blood pressure and urinary catecholamines were normal after surgery.

Catecholamine levels with use of electronic and combustible cigarettes.

Smoking elevates catecholamines that increase the risk for cardiovascular disease. Sparse evidence exists about the effects of e-cigarettes and catecholamines. Higher levels of catecholamines could trigger the increased heart rate, blood pressure, and decreased vascular function reported with the use of e-cigarettes. We investigated the difference in urinary catecholamines and their metabolites before and after the use of an e-cigarette containing nicotine or cigarettes compared to no tobacco use. In our observational cohort exposure study, healthy adults aged 21-45 years who were currently using e-cigarettes, cigarettes, or had never used tobacco, participated in an acute exposure visit using their most common tobacco product. Urine was collected before, 1, and 2 hours after a 3-second puff every 30 seconds for 10 minutes on an e-cigarette or straw or use of 1 cigarette. Urinary catecholamines and their metabolites were measured by ultra-high-performance liquid chromatography. Participants (n=323) were grouped by the product used at the visit. We compared levels of creatinine normalized log-transformed urinary catecholamines and their metabolites across groups using Dunn's test following a Kruskal-Wallis test in unadjusted and demographically adjusted models. Prior to use, individuals who used cigarettes (n=70) had lower urinary metabolites from epinephrine, serotonin, and norepinephrine. No differences were seen in those who used e-cigarettes (n=171) and those who did not use tobacco (n=82). In fully adjusted models, 1 h after the use of a combustible or e-cigarette, log-transformed urinary metabolites from norepinephrine (β=1.22; 95% CI: 0.39-2.05, p=0.004 and β=1.06; 95% CI: 0.39-1.74, p=0.002), dopamine (β=0.37; 95% CI: 0.24-0.5, p<0.001 and β=0.15; 95% CI: 0.05-0.26, p<0.001), and epinephrine (β=1.89; 95% CI: 0.51-3.27, p=0.008 and β=1.49; 95% CI: 0.38-2.61, p=0.009) were elevated. In fully adjusted models, combustible cigarette use was associated with elevated urinary norepinephrine (β=0.46; 95% CI: 0.13-0.81, p=0.007) and dopamine (β=0.19; 95% CI: 0.06-0.31, p=0.003) 1 h after use. We found that the use of both e-cigarettes and cigarettes was associated with elevated urinary catecholamines or their metabolites. Catecholamines could be useful as a biomarker of harm for tobacco use and considered by tobacco regulatory scientists in future research.

Diffuse pulmonary hemorrhage as a rare presentation of pheochromocytoma: a case report with review of the literature

A 37-year-old male patient with a past history of fluctuating hypertension and insulin-treated diabetes mellitus presented to our clinic with a 1-year history of sudden-onset cough, dyspnea, and frank hemoptysis. Examination showed asthenia, moderate anemia, uncontrolled blood pressure, and a past history of one admission for management of hemoptysis and cardiac failure. The evaluation showed mild anemia, azotemia, low ejection fraction, contrast-enhanced computed tomography (CECT) of the chest, and sputum suggestive of pulmonary hemorrhage. Investigation during current admission revealed proteinuria, left suprarenal mass on USG, and clear lung parenchyma on chest X-ray and CECT. Autoimmune workup for vasculitis was negative and 24-h urinary catecholamine levels were elevated with CECT abdomen confirming pheochromocytoma. His blood pressure was controlled and he underwent laparoscopic left adrenalectomy with confirmation on histopathology. Postoperatively he is doing well with minimal requirement of antihypertensive, and diabetes is controlled with diet and exercise only. This case highlights diffuse alveolar hemorrhage as a rare presentation of pheochromocytoma. This case also highlights that secondary cause of hypertension should always be ruled out in case of uncontrolled hypertension in young patients to prevent devastating complications.

Evaluation of pharmacokinetics, safety, and efficacy of [211At] meta-astatobenzylguanidine ([211At] MABG) in patients with pheochromocytoma or paraganglioma (PPGL): A study protocol.

Pheochromocytoma, or paraganglioma (PPGL), is a tumor that arises from catecholamine-producing chromaffin cells of the adrenal medulla or paraganglion. Systemic therapy, such as the combination of cyclophosphamide, vincristine, and dacarbazine or therapeutic radiopharmaceuticals such as [131I] meta-iodobenzylguanidine (MIBG), may be administered in cases of locally advanced tumors or distant metastases. However, the current therapies are limited in terms of efficacy and implementation. [211At] meta-astatobenzylguanidine (MABG) is an alpha-emitting radionuclide-labeled ligand that has demonstrated remarkable tumor-reducing effects in preclinical studies, and is expected to have a high therapeutic effect on pheochromocytoma cells. We are currently conducting an investigator-initiated first-in-human clinical trial to evaluate the pharmacokinetics, safety, and efficacy of [211At] MABG. Patients with locally unresectable or metastatic PPGL refractory to standard therapy and scintigraphically positive [123I] MIBG aggregation are being recruited, and a 3 + 3 dose escalation design was adopted. The initial dose of [211At] MABG is 0.65 MBq/kg, with a dose escalation in a 1:2:4 ratio in each cohort. Dose-limiting toxicity is observed for 6 weeks after a single bolus dose of [211At] MABG, and the patients are observed for 3 months to explore safety and efficacy profiles. The primary endpoint is dose-limiting toxicity to determine both maximum tolerated and recommended doses. The secondary endpoints include radiopharmacokinetics, urinary radioactive excretion rate, urinary catecholamine response rate, objective response rate, progression free survival, [123I] MIBG scintigraphy on reducing tumor accumulation, and quality of life. jRCT2021220012 registered on 17 June 2022.

Effects of Heavy Alcohol Use on Nighttime Blood Pressure, Sleep Quality, and Urine Catecholamines

Heavy alcohol drinking habits contribute to the development of hypertension; this is partly due to overactivation of the sympathetic nervous system and the increased release of catecholamines. Recently, heavy alcohol drinking has been linked to poor sleep quality, but the underlying mechanisms remain unclear. We postulated that long-term frequent heavy alcohol use could increase catecholamine levels and cause blood pressure dysregulation at night, altogether influencing sleep quality. Therefore, the purpose of this study is to test the following hypothesis that compared to non-heavy drinkers, heavy drinkers have a higher level of nighttime catecholamines, a higher levels of nighttime blood pressure, and poorer sleep quality. A total of 44 men and postmenopausal women non-smokers, free of major clinical diseases, were included in this study. Heavy drinkers were defined as those having a dried blood spot phosphatidylethanol (PEth, a biomarker to detect heavy alcohol drinking) level ≥ 20 ng/mL. Participants wore an ambulatory blood pressure monitor for 24 hours and catecholamines were measured from urine samples collected in the same 24-hour period. Sleep quality was measured by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. There were 21 heavy drinkers (mean±SEM for age: 58±1 and BMI: 26.2±0.7 kg/m2) and 23 non-heavy drinkers (age: 58±1 and BMI: 27.5±0.8 kg/m2; P≥0.3 vs. heavy drinkers). Compared to non-heavy drinkers, heavy drinkers had a higher nighttime systolic blood pressure (SBP), higher diastolic blood pressure (DBP), and a lower SBP dipping ratio (heavy drinkers vs. non-heavy drinkers for nighttime SBP: 118±3 vs. 109±2 mmHg, P=0.02; nighttime DBP: 70±2 vs. 65±2 mmHg, P=0.04; and SBP dipping ratio: 10.6±1.4% vs. 14.5±1.6%, P=0.04). No differences were found in nighttime urine catecholamines between heavy drinkers and non-heavy drinkers (P≥0.3). A total of 13 participants had a PSQI score higher than 5, indicating poor sleep quality; however, PSQI scores were similar between heavy and non-heavy drinkers (P=0.8). These findings indicate that heavy drinkers had a higher nighttime blood pressure and are consistent with the observation that heavy drinking is associated with an increased risk of hypertension in mid-life adults. Interestingly, the increase in nighttime blood pressure does not appear to be related to catecholamines and sleep quality in apparently healthy mid-life adults does not appear to be influenced by heavy drinking habits. This work was supported by NIAAA AA028537 to CLH and AHA 1266805160 to TH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150mCi (5.55GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

A retrospective study of paraganglioma of the urinary bladder and literature review.

To review and summarize the characteristics and therapy of paraganglioma of the urinary bladder (PUB). Patients who underwent the operation in Peking Union Medical College Hospital between January 2012 and December 2021 were reviewed for this retrospective study. A total of 29 patients, comprising 9 (31%) men and 20 (69%) women, were included. The main manifestations were hypertension, palpitation, and micturition syncope. Eight patients had an increased 24-h urinary catecholamine, and seven of them had increased norepinephrine. Normetanephrine in seven patients was increased. Six of 18 metaiodobenzylguanidine and 8 of 22 octreotide scans were positive. In total, 15 cases underwent laparoscopic partial cystectomy and 14 underwent transurethral resection of bladder tumor. In all patients, the immunohistochemical index of Melan-A, AE1/AE3, and α-inhibin were negative, and chromogranin A, S-100, and succinate dehydrogenase were positive. The Ki-67 of 28/29 cases was under 5%, and 1 case with a Ki-67 of 20% was diagnosed with malignant PUB. A total of 27 patients had a regular follow-up, 2 patients were lost during the follow-up, 3 patients had a recurrence, and 1 of these patients died within 1 year of surgery. The symptoms all disappeared or were relieved after the surgery. The transurethral surgery approach fits PUB tumors with a size <3 cm or that protrudes into the bladder and can significantly reduce the postoperative hospital stay. Early detection and treatment are effective, and regular review is necessary after the surgery.

Impact of 24 h shifts on urinary catecholamine in emergency physicians: a cross-over randomized trial

24-h shift (24 hS) exposed emergency physicians to a higher stress level than 14-h night shift (14 hS), with an impact spreading on several days. Catecholamines are supposed to be chronic stress biomarker. However, no study has used catecholamines to assess short-term residual stress or measured them over multiple shifts. A shift-randomized trial was conducted to study urinary catecholamines levels of 17 emergency physicians during a control day (clerical work on return from leave) and two working day (14 hS and 24 hS). The Wilcoxon matched-pairs test was utilized to compare the mean catecholamine levels. Additionally, a multivariable generalized estimating equations model was employed to further analyze the independent relationships between key factors such as shifts (compared to control day), perceived stress, and age with catecholamine levels. Dopamine levels were lower during 24 hS than 14 hS and the control day. Norepinephrine levels increased two-fold during both night shifts. Epinephrine levels were higher during the day period of both shifts than on the control day. Despite having a rest day, the dopamine levels did not return to their normal values by the end of the third day after the 24 hS. The generalized estimating equations model confirmed relationships of catecholamines with workload and fatigue. To conclude, urinary catecholamine biomarkers are a convenient and non-invasive strong measure of stress during night shifts, both acutely and over time. Dopamine levels are the strongest biomarker with a prolonged alteration of its circadian rhythm. Due to the relation between increased catecholamine levels and both adverse psychological effects and cardiovascular disease, we suggest that emergency physicians restrict their exposure to 24 hS to mitigate these risks.

A Descriptive Study to Assess the Pre Operative Anxiety Level of the Patients Undergoing Surgery at Apollo Hospitals Bilaspur (C.G.)

Anxiety can be measured in many ways it can be measure directly by measuring plasma cortical and urinary catecholamine , or indirectly by measuring blood pressure and pulse. "An evaluation of patient level of anxiety prior to surgery". The present study was conducted with the objective of A descriptive study to assess the preoperative anxiety level of the patient undergoing surgery and find out association pre anxiety level and demographic variable. The actual data collection by the random sampling technique was used for selection of samples the entire sample fare taken from hospitals. Variables from the study are age, sex, gender, religion , educational status, residence and income, the details and income that tool comprised of personal information causes management general factors . The data was gathered and analysed by calculating mean standard deviation 't' test was used to find out the significance of certain variables and over was calculated for check the reliability of the study findings. We found there are significance association between and demographic variable such as agent residence.

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.

P-02 A case of solitary fibrous tumor originating from the adrenal gland presenting with hypoglycemia

Abstract Introduction Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm usually located in the pleura and associated with NAB2-STAT6 gene fusion. According to the World Health Organization (WHO) classification, although most SFTs are considered well benign, some SFTs have cytological atypia, hypercellularity, tumor necrosis, Ki-67 greater than 5%, high mitotic rate (&amp;gt;4 per high-power field (HPF)) and/or the presence of infiltrative surgical margins are considered malignant. SFT with severe hypoglycemia is called Doege-Potter syndrome which occurs with ectopic secretion of a prohormone of insulin-like growth factor 2 (IGF-2) from tumor tissue. We present a case who applied with severe hypoglycemia and was diagnosed with a solitary fibrous tumor thought to originate from the adrenal gland located in the right retroperitoneal region. Clinical Case A 61-year-old female patient was admitted to the hospital after hypoglycemia was detected in her application due to clouding of consciousness. While the patient's glucose level was 23 mg/dL, insulin:0.4 µIU/mL, C-peptide:&amp;lt;0.01 ng/mL, serum cortisole: 24,20 (µg/mL), growth hormone (GH): 13,20 ng/ mL and insulin-like growth factor I (IGF-1) 38 ng/mL were measured. Insulinoma was excluded and because of IGF-2 level could not be measured in our hospital, low serum insulin and IGF-1 levels suggested high serum IGF-2 levels. HbA1c, adrenal gland, and pituitary function tests were normal (Table 1). A mass lesion of approximately 145×133 mm in size, with heterogeneous contrast, containing cystic areas, was seen, which was thought to originate from the right adrenal gland in the upper abdomen tomography taken due to the presence of a palpable abdominal mass on physical examination (Figure 1). Urine catecholamines were found to be normal, and the plasma aldosterone concentration (PAC)/plasma renin activity (PRA) ratio was 2.56. The patient was operated under intravenous infusion of 10% dextrose due to persistent hypoglycemia. The immunohistochemical evaluation showed CD34, SOX-1 and STAT6 positivity and negativity for S-100, HMB45, straight muscle actin, desmin, caldesmon and melan A, thus confirming the diagnosis of a solitary fibrous tumor. After the operation, the patient's hypoglycemia disappeared. Since there are cases in the literature in which Doege-Potter syndrome was diagnosed without measuring IGF-2, we think that our patient had IGF-2-related hypoglycemia. Conclusion The development of hypoglycemia in Doege-Potter syndrome has been associated with the secretion of large amounts of IGF-2 by tumor tissue, resulting in decreased IGF-1 and Insulin-like growth factor-binding protein 3 (IGFBP-3) concentrations. In these patients, the tumor originates from mesenchymal tumors of low malignant potential. In our case, the Ki-67 proliferation index was around 2%, it was considered benign, and the patient's symptoms completely regressed after resection.Figure 1.CT images of the patientA mass in the right retroperitoneal area, associated with the adrenal gland and containing areas of necrosis, is seen on non-contrast (a) and contrast-enhanced (b) CT scans. Table 1.Laboratory workup

A Sorption–Spectrometric Method for Quantitation of Catecholamines in Urine and Plasma Using Hypercrosslinked Polystyrene and Gold Nanorods or Their Nanocomposites

A Sorption–Spectrometric Method for Quantitation of Catecholamines in Urine and Plasma Using Hypercrosslinked Polystyrene and Gold Nanorods or Their Nanocomposites

Cardiovascular Complications in Pheochromocytoma and Paraganglioma: Does Phenotype Matter?

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. 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. 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. 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.

A Peculiar Cause of Shock: Analysing Two Clinical Cases

Introduction. Pheochromocytoma is a rare neoplasia arising from the adrenal medulla that secretes catecholamines. Those afflicted by this condition can present a wide range of symptoms. One of the most common is paroxysmic hypertension. Interestingly, although rare, some patients present with shock. We describe two cases of pheochromocytoma in which the initial presentation was shock. Case 1. 49 year-old woman, with a history of resistant hypertension, presented to the emergency department with thoracic pain and fever. EKG, echocardiogram (ECC), and myocardial necrosis markers were compatible with Takotsubo syndrome (TS). CT demonstrated a staghorn calculus, hydronephrosis, and signs compatible with xanthogranulomatous pyelonephritis in the right kidney. Additionally, and incidentally, it revealed a 60 mm nodule on the right adrenal gland. Piperacillin/tazobactam was started immediately, and the patient was submitted to urgent upper urinary tract drainage. This procedure was complicated by a cardiorespiratory arrest that was treated with adrenaline administration. The patient was admitted to the ICU due to multifactorial shock and started alpha and, posteriorly, beta blockage. Biochemical adrenal incidentaloma endocrinologic study was negative (under hemodialysis). Multiorgan failure progressively improved. After 2 weeks, the patient was submitted to a laparoscopic transperitoneal right adrenalectomy. No complications were reported. Histological analysis revealed a pheochromocytoma. Case 2. 28-year-old woman presented to the emergency department with headaches and nausea. Vitals were compatible with shock. CT revealed an incidental 72 mm mass on the right adrenal. EKG, ECC, and myocardial necrosis markers were compatible with TS. The patient was started on alpha and, posteriorly, beta blockage. Adrenal incidentaloma endocrinological study demonstrated high urinary catecholamines. Right transperitoneal adrenalectomy was performed. No complications were noted. Histological analysis revealed a pheochromocytoma. Conclusion. Pheochromocytoma can present with complex, enigmatic, and rare clinical pictures. Clinicians should be wary of the possibility of this diagnosis when managing adrenal masses.