Automated online solid-phase extraction-tandem mass spectrometry detection for simultaneous analysis of acidic and alkaline catecholamines and their metabolites in human urine.

Metabolic dysregulation of catecholamines (CAs) is implicated in various human diseases. Simultaneously analyzing these acidic and alkaline CAs and their metabolites poses a significant challenge for clinical detection. This study introduces an efficient method employing automated online solid-phase extraction coupled with tandem mass spectrometry (aoSPE-MS/MS). The method employs weak cation exchange (WCX) and mixed-mode anion exchange (MAX) adsorbents to fabricate an on-line solid-phase extraction (SPE) column, along with an automated injection and multi-valve switching capabilities. The setup allows for automated extraction and analysis of urine samples in 15 minutes while retaining a wide range of acidic and basic CAs and their metabolites. The applicability of this method was demonstrated by optimising the adsorbent dosage volume, extraction solvent, and extraction rate. The limits of detection (LODs) and limits of quantitation (LOQs) for the 8 CAs and their metabolites were determined using the aoSPE-MS/MS approach, with ranges of 0.0625 ∼ 62.5 ng/mL and 0.125 ∼ 125 ng/mL, respectively. Additionally, assessments were made on the linearity, accuracy, and precision within and between batches, as well as matrix and ionic effects, and spiked recoveries. The study discovered that the aoSPE-MS/MS technique simplifies operation, increases efficiency, saves time, and has low detection and quantification limits when detecting a wide range of acid and alkaline CAs and their metabolites in urine. The study successfully demonstrated the high-throughput and automated detection of the 8 CAs and their metabolites with varying acidity and alkalinity in human urine samples. This method is expected to be a potential powerful tool for clinical detection.

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.

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.

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.

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.

Machine-learning assisted multiplex detection of catecholamine neurotransmitters with a colorimetric sensor array.

Catecholamine neurotransmitters (CNs), such as dopamine (DA), epinephrine (EP), norepinephrine (NEP), and levodopa (LD), are recognized as the primary biomarkers of a variety of neurological illnesses. Therefore, simultaneous monitoring of these biomarkers is highly recommended for clinical diagnosis and treatment. In this study, a high-performance colorimetric artificial tongue has been proposed for the multiplex detection of CNs. Different aggregation behaviors of gold nanoparticles in the presence of CNs under various buffering conditions generate unique fingerprint response patterns. Under various buffering conditions, the distinct acidity constants of CNs, and consequently their predominant species at a given pH, drive the aggregation of gold nanoparticles (AuNPs). The utilization of machine learning algorithms in this design enables classification and quantification of CNs in various samples. The response profile of the array was analyzed using the linear discriminant analysis algorithm for classification of CNs. This colorimetric sensor array is capable of accurately distinguishing between individual neurotransmitters and their combinations. Partial least squares regression was also applied for quantitation purposes. The obtained analytical figures of merit (FOMs) and linear ranges of 0.6-9 µM (R2 = 0.99) for DA, 0.1-10 µM (R2 = 0.99) for EP, 0.1-9 µM (R2 = 0.99) for NEP and 1-70 µM (R2 = 0.99) for LD demonstrated the potential applicability of the developed sensor array in precise and accurate determination of CNs. Finally, the feasibility of the array was validated in human urine samples as a complex biological fluid with LODs of 0.3, 0.5, 0.2, and 1.9 µM for DA, EP, NEP, and LD, respectively.

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.

Catecholamines in neuroblastoma: Driver of hypertension, or solely a marker of disease?

BACKGROUND: Neuroblastoma is a common solid tumor of childhood and is often associated with hypertension. Potential etiologies contributing to hypertension include renal compression, pain, volume overload, and catecholamine secretion. CASES: We completed a single center retrospective review of children with neuroblastoma and ≥stage II hypertension (per Hypertension Canada guidelines) over a 2-year period. All patients (n = 10) had elevated urine normetanephrine levels and eight had intra-abdominal tumors. Four patients had refractory hypertension requiring > three agents, of which three required alpha/beta blockade. CONCLUSION: Although multifactorial, hypertension in neuroblastoma often has a neuroendocrine component. Excess normetanephrine production in neuroblastoma may be a more common hypertensive mechanism than previously appreciated. Urinary normetanephrine elevation could suggest potential neuroendocrine-mediated hypertension.

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.

Repeated Oral Administration of Flavan-3-ols Induces Browning in Mice Adipose Tissues through Sympathetic Nerve Activation.

We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS). In this study, we confirmed the marked increase in urinary catecholamine (CA) s projecting SNS activity following a single dose of 50 mg/kg FLs. In addition, we examined the impact of the repeated administration of 50 mg/kg FLs for 14 days on adipose tissues in mice. In BAT, FLs tended to increase the level of Ucp-1 along with significant increase of thermogenic transcriptome factors expressions, such as peroxisome proliferator-activated receptor γ coactivator (PGC)-1α and PR domain-containing (PRDM)1. Expression of browning markers, CD137 and transmembrane protein (TMEM) 26, in addition to PGC-1α were increased in epididymal adipose (eWAT) by FLs. A multilocular morphology with cell size reduction was shown in the inguinal adipose (iWAT), together with increasing the level of Ucp-1 by FLs. These results exert that FLs induce browning in adipose, and this change is possibly produced by the activation of the SNS.

Neuroblastoma Screening at 1 Year of Age: The Final Results of a Controlled Trial.

Background: Neuroblastoma screening aims to reduce neuroblastoma-related mortality. A controlled trial showed no reduction in stage 4 disease incidence and preliminary mortality data. This article presents epidemiologic and clinical data 20 years after cessation of the screening program. Methods: The patients with detected disease in the screening area were compared with the clinically diagnosed patients in the control area and in the prestudy and poststudy cohorts. All statistical tests were 2-sided. Results: The cumulative incidence for children aged 1 to 6 years in the birth study cohorts (1994-1999) in the screening arm was 13.4 cases per 100 000 births (95% confidence interval [CI] = 12.2 to 14.6) based on 61.2% of screening participants and 38.8% of nonparticipants. Screening participants had a cumulative incidence of 15.7 (95% CI = 14.0 to 17.4) per 100 000 births. The cumulative incidence in the contemporary control cohort was 9.3 (95% CI = 8.2 to 10.3) per 100 000 births, 7.6 (95% CI = 6.8 to 8.4) in the prestudy cohort, and 8.1 (95% CI = 7.4 to 8.9) in the poststudy cohort from 2000 to 2004 (P < .001 each). The increased incidence in the screening cohort was restricted to stages 1 through 3, while stage 4 incidence was not reduced. The cumulative mortality for deaths within 10 years from diagnosis and per 100 000 births remained unchanged. Patients with stage 4 disease detected by screening had better biological characteristics and an improved outcome compared with those stage 4 cases not detected by screening. Conclusions: Neuroblastoma screening at 1 year of age reduced neither stage 4 incidence nor neuroblastoma mortality and was affected by overdiagnosis, leading to unnecessary treatment. A few screening-detected stage 4 cases represent a biologically interesting subgroup but do not change the recommendation to close the "catecholamine-based neuroblastoma screening book."

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.

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.

Pheochromocytoma: A three-decade clinical experience in a multicenter study.

OBJECTIVE: To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). DESIGN AND METHODS: A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. RESULTS: A total of 106 patients (61 [57.5%] women, mean age 52.3 ±â€¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ±â€¯14.2 years vs 54.5 ±â€¯13.9 years, p < .001). Familial PCCs were more frequently associated with MEN2A (n = 8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3 cm (3-6 cm); 27.7% of the patients had tumors ≥6 cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4 cm [2.4-5.0 cm] vs 5.6 cm [4.0-7.0 cm], p < .001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). CONCLUSIONS: PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.

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.

Urinary Catecholamines as Markers in Overtraining Syndrome.

In this study, potential urinary markers that show the presence of overtraining syndrome (OTS) were investigated. After a hard training period without an optimal recovery, OTS could appear in athletes. This syndrome could result in a decreasing of performance, a state of chronic fatigue and a not well-being state. The search for markers that demonstrate the presence of OTS could prevent the physiological and psychological health of the athletes, improving the performance.In this chapter, we will analyze some studies that have examined biochemical, physiological, and immunological markers of overtraining in urine and the variation of the catecholamines in a situation of stressed training.

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.