Urinary Norepinephrine Research Articles

Continuous positive airway pressure therapy reduces the levels of catecholamines and blood pressure in pseudophaeochromocytoma with coexisting obstructive sleep apnoea.

BackgroundStress from obstructive sleep apnoea (OSA) stimulates catecholamine release and consequently can exacerbate hypertension, even in the absence of a catecholamine-producing tumour (phaeochromocytoma). As such, a positive screening test for suspected phaeochromocytoma may be misleading. There exists only a handful case reports, and no controlled trials, how continuous positive airway pressure (CPAP) to treat OSA influences catecholamine levels. We examined changes to levels of urinary catecholamine and blood pressure in response to CPAP treatment.MethodsWe conducted a meta-analysis of data aggregated from published case reports of individual patient data up to April 2020. The quality of the reports was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool.ResultsA total of 13 cases (seven men and six women) from seven reports met our search criteria. Patients had mean age of 49.1 years (range = 36–62) and body mass index of 37.4 kg/m2 (range = 27–56). Most had moderate to severe OSA with CPAP treatment. Nine cases had 24-hour urinary noradrenaline assessment before and after CPAP treatment. CPAP treatment led to a 21% reduction (104 nmol/24-hours, 95% credible interval =59 to 148) in 24-hour urinary noradrenaline to within reference ranges, and 25% reduction (from 131 to 100 mmHg) in mean arterial pressure. The risk of overall bias evaluated by the ROBINS-I tool was found to be low in the majority of reports.ConclusionsInvestigations of patients suspected of phaeochromocytoma, particularly obese individuals, should exclude OSA and treat this condition if present before performing screening tests to assess for catecholamine levels.

Seasonal variation of blood pressure in children

Seasonal blood pressure (BP) variation is mostly found between the summer and winter months. Guidelines for diagnosis and treatment of hypertension in children have not considered this variation until recently. This review aims to present an overview of seasonal BP variation in childhood along with potential underlying pathophysiological mechanisms and long-term implications as well as conclusions for future studies. In pediatric cohorts, seven studies investigated seasonal changes in BP. These changes amount to 3.4–5.9 mmHg (or 0.5–1.5 mmHg per − 1 °C difference in environmental temperature) in systolic BP with a peak in fall or winter. Potential mechanisms and mediators of seasonal BP variation include sympathetic activation of the nervous system with an increase of urinary and plasma norepinephrine levels in the winter season. Additionally, the physical activity among children and adolescents was inversely correlated with BP levels. Temperature sensitivity of BP and pediatric BP levels predict future systolic BP and target-organ damage. Therefore, cardiovascular events may even be long-term complications of seasonal BP variation in pediatric hypertensive patients. Overall, these data strongly suggest an important effect of ambient temperature on BP in children. Additional studies in pediatric cohorts are needed to define how best to incorporate such variation into clinical practice.

Inhibition of α2-adrenoceptor is renoprotective in 5/6 nephrectomy-induced chronic kidney injury rats

In the present study, we investigated the renoprotective effects of long-term treatment with yohimbine, an α2-adrenoceptor inhibitor, in a 5/6 nephrectomy-induced chronic kidney disease (CKD) rat model. Male Sprague–Dawley rats were randomly allocated into the following groups: sham-operated, 5/6-nephrectomized (5/6 Nx), 5/6 Nx + low or high dose of yohimbine (0.3 or 3.0 mg/L in drinking water, respectively), and 5/6 Nx + hydralazine (250 mg/L in drinking water). The 5/6 Nx group presented with renal dysfunction, hypertension, noradrenaline overproduction, and histopathological injuries. Blood pressure decreased in both the yohimbine- and hydralazine-treated groups. Treatment with high dose of yohimbine, but not hydralazine, apparently attenuated urinary protein excretion and noradrenaline concentration of renal venous plasma. Renal fibrosis and upregulated fibrosis-related gene expression were suppressed by high dose of yohimbine. Furthermore, yohimbine, but not hydralazine, treatment ameliorated the urinary concentration ability. These findings suggest that long-term yohimbine treatment can be a useful therapeutic option to prevent the progression of CKD.

Quantitation using HRMS: A new tool for rapid, specific and sensitive determination of catecholamines and deconjugated methanephrines metanephrines in urine

Urinary catecholamines and their methylated metabolites are biochemical indicators of pheochromocytoma, paraganglioma and neuroblastoma. A rapid and precise analytical method based on solid-phase extraction (SPE) and liquid chromatography separation coupled to high-resolution mass spectrometry (LC-HRMS) was developed and validated to measure urinary catecholamines (epinephrine (E), norepinephrine (NorE), dopamine (D)) and total methylated metabolites (normetanephrine (NorMN), metanephrine(MN) and 3-methoxytyramine (3-MT)) in a clinical setting. Results of 51 urine specimens measured using this LC-HRMS method were compared with a liquid chromatography assay with electrochemical detection (LC-EC). Urine samples (200 μL) were spiked with an internal standard solution followed by SPE purification. In the case of total methylated metabolites, urine was hydrolyzed before SPE purification. Separation was achieved on an Acclaim Mixed Mode WCX column, with an 8.5 min runtime. All compounds were detected in electrospray positive ionization mode with a parallel reaction monitoring acquisition and quantified with a linear regression (r2 > 0.998) between 2 and 200 µg/L (10.9–1090; 11.8–1182 nmol/L) for E and NorE respectively and between 10 and 1000 µg/L for others (65.2–6520; 50.7–5070; 54.5–5450 ; 59.8–5980 nmol/L for D, M, NorMN and 3-MT, respectively). Overall imprecision and bias did not exceed 15%. No significant matrix effect was observed. Correlation between the two assays was good except for epinephrine. Epinephrine concentrations measured by LC-EC method were slightly higher than values obtained with LC-HRMS method but without impact on clinical decision. This LC-HRMS assay provides a new tool for simultaneous quantitative catecholamine determination and was successfully applied in routine for the screening or follow up of pheochromocytoma, paraganglioma and neuroblastoma. LC-HRMS method offers significant advantages compared to LC-EC with good sensitivity, an unambiguous analyte determination and high sample throughput.

Smoking Accelerates Atrioventricular Conduction in Humans Concordant with Increased Dopamine Release.

Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.

Study to Evaluate Stress Among Ophthalmic Surgeons with Different Levels of Surgical Experience.

AimTo assess and quantify the stress in two different groups of ophthalmic surgeons while performing cataract surgery.Materials and MethodsThis is a prospective observational institutional study. Healthy ophthalmic surgeons (4 trainee surgeons and 4 consultants) and 4 OT assistants without any history of systemic illness were studied while performing uncomplicated and uneventful cataract surgery. Resting state and post-operative (immediately after surgery) systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), and oxygen saturation (SPO2) were measured by a Comen C80 multi-parameter monitor. Blood cortisol levels were measured by chemiluminescent assay (CLIA) and urine catecholamines levels (adrenaline, nor-adrenaline and dopamine) were measured by high performance liquid chromatography (HPLC). For assessment of stress among one group, paired t-test is used and for comparison of stress levels between trainee surgeons and consultants unpaired t-test is used.ResultsConsultants performed phacoemulsification and trainee surgeons performed small incision cataract surgery. In both the groups, the post-operative values of SBP, DBP, PR, blood cortisol, and urine catecholamines were significantly higher than the pre-operative values. This difference was statistically significant. There was a significantly higher increase in SBP, DBP, PR, blood cortisol, urine adrenaline, and urine dopamine in trainee surgeons as compared to consultants whereas there was a significantly higher increase in urine nor-adrenaline in consultants as compared to trainee surgeons.ConclusionOur study reveals that every surgeon is under stress irrespective of experience though the level of stress is different among surgeons.

Meta-analysis of changes in the levels of catecholamines and blood pressure with continuous positive airway pressure therapy in obstructive sleep apnea.

Stress from obstructive sleep apnea (OSA) stimulates catecholamine release consequently exacerbating hypertension. However, different studies have shown a conflicting impact of continuous positive airway pressure (CPAP) treatment in patients with OSA on catecholamine levels and blood pressure. We aimed to examine changes to catecholamine levels and blood pressure in response to CPAP treatment. We conducted a meta‐analysis of data published up to May 2020. The quality of the studies was evaluated using standard tools for assessing the risk of bias. Meta‐analysis was conducted using RevMan (v5.3) and expressed in standardized mean difference (SMD) for catecholamines and mean difference (MD) for systolic (SBP) and diastolic blood pressure (DBP). A total of 38 studies met our search criteria; they consisted of 14 randomized control trials (RCT) totaling 576 participants and 24 prospective cohort studies (PCS) of 547 participants. Mean age ranged between 41 and 62 year and body mass index between 27.2 and 35.1 kg/m2. CPAP treatment reduced 24‐hour urinary noradrenaline levels both in RCT (SMD = −1.1; 95% confidence interval (CI): −1.63 to − 0.56) and in PCS (SMD = 0.38 (CI: 0.24 to 0.53). SBP was also reduced by CPAP treatment in RCT (4.8 mmHg; CI: 2.0‐7.7) and in PCS (7.5 mmHg; CI: 3.3‐11.7). DBP was similarly reduced (3.0 mmHg; CI: 1.4‐4.6) and in PCS (5.1 mmHg; CI: 2.3‐8.0). In conclusion, CPAP treatment in patients with OSA reduces catecholamine levels and blood pressure. This suggests that sympathetic activity plays an intermediary role in hypertension associated with OSA‐related stress.

Differential Responses of Urinary Epinephrine and Norepinephrine to 24-h Shift-Work Stressor in Physicians.

Multiple stressors, including 24-h-shifts characterise the working environment of physicians, influencing well-being, health and performance. We aimed to evaluate the effect of the stressor 24-h-shift on the adrenal medullary and sympathoneural system in physicians with the hypothesis that shift work might have different impacts on both systems. Twenty-two physicians collected two 12-h-urine samples (“daytime” and “nighttime”) during a 24-h shift (“on-duty”) and on a free weekend (“off-duty”), respectively. Urinary excretion rates per m2 body surface area were assessed for the catecholamines epinephrine, norepinephrine and their respective free O-methylated metabolites metanephrine and normetanephrine by LC-MS/MS-analysis. The stressor provoked differential responses of epinephrine and norepinephrine. Epinephrine excretion rates showed significant increases from off to on duty. The largest proportional change (off-duty to on-duty) for epinephrine was observed for nighttime (205%), the increase for daytime was 84%. An increase in norepinephrine from off to on duty was only visible for nighttime collections. For the catecholamine metabolites, normetanephrine paralleled norepinephrine and exhibited an increase in excretion from off to on duty during nighttime collections of 53% whereas there was no change during daytime collections (3%). In conclusion: Whilst the 24-h-shift-work stressor in physicians activates the sympatho-adrenomedullary system, represented by epinephrine, the sympathoneural response through norepinephrine reflects mainly an ambulatory position during working hours.

Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH).

Thyrotropin-releasing hormone (TRH) plays several roles as a hormone/neuropeptide. Diencephalic TRH (dTRH) participates in the regulation of blood pressure in diverse animal models, independently of the thyroid status. The present study aimed to evaluate whether chronic overexpression of TRH in mice affects cardiovascular and metabolic variables. We developed a transgenic (TG) mouse model that overexpresses dTrh. Despite having higher food consumption and water intake, TG mice showed significantly lower body weight respect to controls. Also, TG mice presented higher blood pressure, heart rate, and locomotor activity independently of thyroid hormone levels. These results and the higher urine noradrenaline excretion observed in TG mice suggest a higher metabolic rate mediated by sympathetic overflow. Cardiovascular changes were impeded by siRNA inhibition of the diencephalic Trh overexpression. Also, the silencing of dTRH in the TG mice normalized urine noradrenaline excretion, supporting the view that the cardiovascular effects of TRH involve the sympathetic system. Overall, we show that congenital dTrh overexpression leads to an increase in blood pressure accompanied by changes in body weight and food consumption mediated by a higher sympathetic overflow. These results provide new evidence confirming the participation of TRH in cardiovascular and body weight regulation.

HMB-45 Negative Adrenal Angiomyolipoma With A Synchronous Adrenal Adenoma – An Unusual Association

Background:&#x0D; Angiomyolipoma (AML) is an uncommon mesenchymal tumour usually found in the kidney. The most common extrarenal site is usually the liver. We report a case of adrenal AML with a predominant vascular component co-existing with an adrenal adenoma.&#x0D; Case report: &#x0D; A fifty-year-old male presented with two months history of dysuria. Computed tomography showed a heterogeneous lesion involving the right adrenal gland abutting the right kidney and adjacent liver capsule. Urine noradrenaline levels were elevated. Adrenalectomy specimen showed an encapsulated mass measuring 8 x 5 x3.5 cm with a lobulated, grey to tan brown cut surface with areas of haemorrhage and tiny cystic spaces. Another yellowish nodule measuring 1.3 x 1.2 x 1 cm was also noted at one pole. Microscopy showed a neoplasm composed predominantly thick-walled vascular channels admixed with foci of smooth muscle bundles and adipocytes. Yellowish nodule showed features of adrenal adenoma. HMB-45 was negative and CD34 positivity highlighted the thick and thin walled vessels.&#x0D; Conclusion: &#x0D; We present the very first case of HMB-45 negative adrenal AML with a predominant vascular component and a synchronous adrenal adenoma.

TRPV1 Activation Prevents Renal Ischemia-Reperfusion Injury-Induced Increase in Salt Sensitivity by Suppressing Renal Sympathetic Nerve Activity.

: BackgroundSalt sensitivity is increased following renal Ischemia-Reperfusion (I/R) injury. We tested the hypothesis that high salt intake induced increase in Renal Sympathetic Nerve Activity (RSNA) after renal I/R can be prevented by activation of Transient Receptor Potential Vanilloid 1 (TRPV1).MethodsRats were fed a 0.4% NaCl diet for 5 weeks after renal I/R, followed by a 4% NaCl diet for 4 more weeks in four groups: sham, I/R, I/R +High Dose Capsaicin (HDC), and I/R+Low Dose Capsaicin (LDC). The low (1mg/kg) or high (100mg/kg) dose of capsaicin was injected subcutaneously before I/R to activate or desensitize TRPV1, respectively.ResultsSystolic blood pressure was gradually elevated after fed on a high-salt diet in the I/R and I/R+HDC groups but not in the I/R+LDC group, with a greater increase in the I/R+HDC group. Renal function was impaired in the I/R group and was further deteriorated in the I/R+HDC group but was unchanged in the I/R+LDC group. At the end of high salt treatment, afferent renal nerve activity in response to unilateral intra-pelvic administration of capsaicin was decreased in the I/R group and was further suppressed in the I/R+HDC group but was unchanged in the I/R+LDC group. RSNA in response to intrathecal administration of muscimol, a selective agonist of GABA-A receptors, was augmented in the I/R group and further intensified in the I/R+HDC group but was unchanged in the I/R+LDC group. Similarly, urinary norepinephrine levels were increased in the I/R group and were further elevated in the I/R+HDC group but unchanged in the I/R+LDC group.ConclusionThese data suggest that TRPV1 activation prevents renal I/R injury-induced increase in salt sensitivity by suppressing RSNA.

Carbidopa for Afferent Baroreflex Failure in Familial Dysautonomia: A Double-Blind Randomized Crossover Clinical Trial.

Afferent lesions of the arterial baroreflex occur in familial dysautonomia. This leads to excessive blood pressure variability with falls and frequent surges that damage the organs. These hypertensive surges are the result of excess peripheral catecholamine release and have no adequate treatment. Carbidopa is a selective DOPA-decarboxylase inhibitor that suppresses catecholamines production outside the brain. To learn whether carbidopa can inhibit catecholamine-induced hypertensive surges in patients with severe afferent baroreflex failure, we conducted a double-blind randomized crossover trial in which patients with familial dysautonomia received high dose carbidopa (600 mg/day), low-dose carbidopa (300 mg/day), or matching placebo in 3 4-week treatment periods. Among the 22 patients enrolled (13 females/8 males), the median age was 26 (range, 12-59 years). At enrollment, patients had hypertensive peaks to 164/116 (range, 144/92 to 213/150 mm Hg). Twenty-four hour urinary norepinephrine excretion, a marker of peripheral catecholamine release, was significantly suppressed on both high dose and low dose carbidopa, compared with placebo (P=0.0075). The 2 co-primary end points of the trial were met. The SD of systolic BP variability was reduced at both carbidopa doses (low dose: 17±4; high dose: 18±5 mm Hg) compared with placebo (23±7 mm Hg; P=0.0013), and there was a significant reduction in the systolic BP peaks on active treatment (P=0.0015). High- and low-dose carbidopa were similarly effective and well tolerated. This study provides class Ib evidence that carbidopa can reduce blood pressure variability in patients with congenital afferent baroreflex failure. Similar beneficial effects are observed in patients with acquired baroreflex lesions.

MON-915 Acute Abdominal Pain and the Pheochromocytoma

Background:Pheochromocytomas are neuroendocrine tumors that release large amounts of metanephrines and catecholamines, resulting in a wide array of symptoms including hypertension, diaphoresis, and headaches. If left unrecognized they can lead to serious morbidity including ischemic or hemorrhagic CVA, encephalopathy, MI, Aortic Dissection, and renal injury.Clinical Case:A 62-year-old male began having difficulties with his blood pressure over the past year. He was first hospitalized for an acute ischemic CVA with hypertensive urgency. His blood pressure was generally controlled throughout the admission but he continued to have intermittent elevations. After transferring to an inpatient rehabilitation unit he had an episode of acute nausea, severe lower abdominal pain, and emesis following dinner. He was tachycardic and hypertensive up to 190/115. Acute abdominal imaging revealed constipation but no obstruction. His symptoms resolved, returning a few hours later with another episode of acute nausea, vomiting, and severe lower abdominal pain, with blood pressure 210/126 and tachycardia. IV Metoprolol, Hydralazine and pain medications did not significantly improve his blood pressure, he was subsequently started on a Nitroglycerin drip. Abdominal workup was unremarkable, he was stabilized and discharged back to rehabilitation on increased oral medications. He continued to have blood pressure spikes up to 200/124 with nausea, vomiting, and severe abdominal pain until a Clonidine patch was started, after which his blood pressure was better controlled. He was discharged home with continued outpatient therapies.A few weeks later he returned to the ER with nausea and severe abdominal pain, blood pressure at home was 254/185. On exam he was diaphoretic, tachycardic, and tachypneic. A CTA scan was obtained without signs of dissection. A Nitro drip with IV push Hydralazine were not effective at controlling his blood pressure, and so Lisinopril, Amlodipine, and a Clonidine patch were added. Over the next few days he had progressively fewer hypertensive elevations and his symptoms were only present during hypertensive episodes. An extensive workup for secondary hypertension was started. 24-hour plasma and urine Metanephrines were within normal limits. Urine Normetanephrine was elevated to 1266 ug/24h (Ref 88-444). Urine Norepinephrine was elevated to 124 ug/24h (Ref 15-80), Urine Dopamine was elevated to 578 ug/24h (Ref 65-400), and total Catecholamines were elevated to 133 ug/24h (Ref 15-100).Conclusion:This case illustrates the variance in presentations for Pheochromocytoma and the importance of maintaining a high index of suspicion for secondary causes in patients with intractable hypertension. While commonly reported symptoms include nausea and hypertension, the presentation of acute abdominal pain as the primary complaint is also an important feature of this disease.

MON-903 Sporadic Phaeochromocytoma, Pancreatic Neuroendocrine Tumour and a Sacral Hibernoma: A Case Report

Most phaeochromocytomas and pancreatic neuroendocrine tumours are sporadic in nature however the presence of multiple neuroendocrine tumours raises the suspicion of a hereditary endocrinopathy. Hibernomas, benign tumours that morphologically resemble brown fat, do not possess a clear aetiology and a link with other neuroendocrine tumours remains unclear. We report an unusual case of a concurrent sporadic phaeochromocytoma, pancreatic neuroendocrine tumour and a sacral hibernoma. A 61 year old female presented with a 3 month history of abdominal pain which led to the discovery of a lesion in her right adrenal gland and a soft tissue mass at the pancreatic tail on a CT Abdomen. The adrenal lesion was biochemically suggestive of a phaeochromocytoma (plasma normetanephrine 4930 pmol/L, plasma 3-methoxytyramine 580 pmol/L, urinary noradrenaline 5564 pmol/day, urinary dopamine 4720 nmol/day). A 68Ga-DOTATATE-PET-CT scan revealed DOTATATE avid lesions in the right adrenal gland, tail of pancreas and right sacral ala. Following preoperative medical therapy, the patient underwent a right adrenalectomy and a resection of the distal pancreatic lesion.Histopathology confirmed a phaeochromocytoma with no conscipicouous mitotic activity, and the pancreatic tail lesion was consistent with a well-differentiated neuroendocrine tumour (NET) (Ki-67 score <3%). Following normalisation of the serum catecholamines, a biopsy of the sacral lesion was undertaken, which returned positive for a hibernoma. Genetic testing revealed no identifiable genetic mutations.This case reports the synchronous presence of a phaeochromocytoma, pancreatic NET and sacral hibernoma with no identifiable genetic mutation. To date, the association between hibernomas and neuroendocrine tumours has not been fully established, but a few case reports suggest a possible association between MEN1 and hibernomas.

MON-LB034 A Severe Case of Pheochromocytoma Presenting as Classic Takotsubo’s Cardiomyopathy With Rapid Resolution

Background: Inverted Takotsubo’s cardiomyopathy requiring extra-corporeal membrane support (ECMO) with pheochromocytoma is well described. Classic Takotsubo’s cardiomyopathy, however, is rarely described in this setting. Clinical Case: A 50-year old woman with no previous comorbidities presented with pulmonary edema and cardiogenic shock. She required rapid escalation of vasopressor, inotrope, and intra-aortic balloon pump then ECMO with consideration of cardiac transplant. Initial echocardiogram showed an ejection fraction of 17%. Coronary angiography showed apical ballooning in keeping with classic Takotsubo’s cardiomyopathy. Abdominal ultrasound for transplant screening showed a 4.6 cm abdominal mass. Computed tomography confirmed a 4.6 cm mass with classic radiologic features of pheochromocytoma. Plasma free normetaphrine and metanephrine were elevated at 2.34 nmol/L and 0.25 nmol/L. A 24-hour urine collection included urine volume of 3500 ml, urine creatinine 7.2 mmol/day, elevated urine norepinephrine 1199 nmol/day, elevated urine epinephrine 888 nmol/day, and normal urine dopamine 335 nmol/day. Parathyroid hormone and calcitonin were normal at 0.4 pmol/L and 4.8 pmol/L, respectively. Plasma aldosterone was normal at 87 pmol/L and plasma renin normal at 3.5 ng/L. Doxazosin 1 mg daily was initiated and she had clinical improvement next day and came off ECMO. Her ejection fraction improved to 55% subsequent week. She had retroperitoneoscopic adrenalectomy two weeks later with full recovery. Conclusion: Classic Takotsubo’s cardiomyopathy is a possible presentation of pheochromocytoma with rapid resolution with alpha blockade.

SAT-199 Diagnostic Dilemma: An Adrenal Incidentaloma in a Young Adult

Introduction:In an adult endocrine clinic, the majority of patients referred for evaluation of an adrenal incidentaloma are older than 30 years of age. It is important to be reminded that a patient may be diagnosed with an adrenal mass at any age but the etiology may vary depending on the age at presentation.Clinical case:An 18 year-old African American female with no significant past medical problems presented with a 2 month history of flank and abdominal pain associated with nausea and vomiting. An abdominal CT scan and a dedicated adrenal CT showed a right adrenal mass measuring 2.2 x 2.6 cm. The noncontrast Hounsfield units were 23, enhanced Hounsfield units 210, and delayed Hounsfield units 72. The calculated washout was 44%, not consistent with an adrenal adenoma. An MRI of the abdomen showed a 2.5 cm right adrenal nodule. The lesion did not demonstrate significant loss of signal between in and out of phase imaging, therefore the characteristics were not consistent with a lipid rich adenoma. Laboratory tests included an ACTH of 31 pg/mL (6-48 pg/mL), cortisol 8.7 ug/mL at 10:57 am (7-9 am 5.27-22.45 ug/mL), aldosterone 10.1 ng/dL (6-48 ng/dL), renin 2.2 ng/mL/hr (upright 0.5-4.0 ng/mL/hr), DHEA-sulfate 129 ug/dL (44-248 ug/dL), plasma free metanephrine 0.10 nmol/L (0.00-0.49 nmol/L), and plasma free normetaneprhine 0.41 nmol/L (0.00-0.89 nmol/L). The 24-hour urine norepinephrine, epinephrine, and metanephrine were all normal, however the 24-hour urine dopamine was elevated, 824 ug/24 hrs (52-480 ug/24 hrs). Subsequently, plasma dopamine, norepinephrine, and epinephrine were all within the reference range. The patient had a robotic-assisted right adrenalectomy removing a 5.7 x 3.5 x 1.7 cm gland, weighing 16.3 grams. The pathology demonstrated a ganglioneuroma within the right adrenal gland measuring 2.2 x 2.0 x 2.7 cm, negative for neuroblastoma or blastic components. Focal hemorrhage was noted, there was no tumor necrosis, and no mitotic figures were present. The tumor appeared to be encapsulated in the adrenal gland and the Ki-67 stain was negative in ganglioneuroma cells.Conclusion:Adrenal adenomas that appear as incidentalomas in young adulthood are extremely rare. Evaluating younger versus older adults found to harbor an adrenal “incidentaloma“ requires a unique approach for each age group, as the differential diagnosis varies widely. In our patient, the imaging was extremely concerning and diagnostic considerations included neuroblastoma, adrenocortical malignancy, pheochromocytoma, or ganglioneuroma. Adrenal ganglioneuromas are most frequently diagnosed in fourth and fifth decades of life. In younger adults ganglioneuromas are usually found in the retroperitoneum and posterior mediastinum. For our patient, surgical resection of the adrenal mass confirmed the pathologic diagnosis and provided definitive cure.

SAT-195 The Diagnosis and Management of a Functional Paravertebral Paraganglioma

A 32-year-old male presented with a 4-year history of palpitations, diaphoresis, and orthostatic hypotension. One year prior to presentation, he began experiencing severe, episodic headaches and neck pressure. Neurological work-up included an MRI head, neck, and spine, identifying a left posterior mediastinal lesion adjacent to the T5 vertebral body, approximately 2.4 x 2.0 cm. A community surgical center attempted mass resection via Video -assisted (VATS) approach. Resection was aborted intraoperatively due to a hypertensive crisis following lesion manipulation, with his systolic blood pressure increasing above 325 mmHg.Subsequent evaluation revealed a 24-hour urine norepinephrine of 6117 nmol/d (normal <575) and normetanephrines of 16.6 umol/d (normal <3.4). An MIBG study showed intense tracer avidity in the left paraspinal lesion and minimal uptake in the adrenal glands.A functional paravertebral paraganglioma was diagnosed and the patient was initiated on alpha and beta-blockade in preparation for staged combined treatment.Spinal angiography was performed to define the arterial supply of spinal cord and tumor, which confirmed a hypervascular left thoracic paraspinal tumor. Arterial supply emanated from the left T4 intercostal and left supreme intercostal arteries and a prominent draining vein was present. Trans-arterial particle embolization was performed via both arteries with minimal residual tumor blush present post procedure.Successful VATS excision of the tumor was completed one week after arterial embolization with minimal blood loss. Pathology of the resected tumor revealed an overall intact tumor that stained diffusely positive with synaptophysin and sustentacular cells highlighted by S100 protein with a few foci of coagulative necrosis.Episodes of hypertension (maximum BP 210/80) occurred during embolization and surgical resection with vascular manipulation. These were managed with intraoperative nitroprusside and phentolamine. Peri-procedural plasma metanephrine and cathecholamine levels were collected. Normetanephrine levels (normal <=0.89 nmol/L) were 4.66 before embolization, >6.25 after embolization, 3.70 the day after embolization, 4.10 before VATS, and 0.69 after VATS. Norepinephrine levels (normal 0.8–3.4 nmol/L) were 24.3, 111.7, 61.1, 19.6, and 4 respectively. Genetic testing showed no hereditary predisposition.Discussion:Functional neuroendocrine tumours may be difficult to diagnose due to the wide variety of clinical presentations and must be considered when investigating a vascular mediastinal tumor. In our case, pre-operative embolization did not normalise plasma catecholamine levels, likely from incomplete arterial embolization, but helped reduce intra-operative surgical bleeding risk. Alpha- and beta-blockade should be continued until surgical resection, with dose adjustment as required.

SUN-LB38 Adrenal Tumor Causing Unexplained Hyperhidrosis in a Young Man

Introduction: Pheochromocytoma is a rare neuroendocrine tumor, afflicting around 0.8 out of 100,000 people per year [1]. The “classic triad” of headache, diaphoresis, and tachycardia is well documented in the literature. The “classic triad” in combination with hypertension has up to 91% sensitivity and 93.5% specificity for the diagnosis of pheochromocytoma [2]. Generalized sweating is part of the “classic triad”, however there is paucity of evidence in the literature describing diaphoresis as the only presenting symptom of pheochromocytoma.Case description: A 20-year-old male presented with five year history of worsening hyperhidrosis without any other associated symptoms. Vital signs were blood pressure of 138/82 mmHg and heart rate of 60 bpm. The remainder of the physical exam was normal. Laboratory testing showed 24 hour urine norepinephrine level of 1,002 ug/24 hours (normal: 0-135 ug/24hrs), plasma normetanephrine was 2,873 pg/mL (normal: 0-145 pg/mL) and plasma norepinephrine was 2,869 pg/mL (normal: 0-874 pg/mL). CT abdomen revealed a 4.0 x 3.1 x 4.3 cm left adrenal mass. After appropriate preoperative preparation, he successfully underwent a laparoscopic left adrenalectomy with complete resolution of diaphoresis. Pathology confirmed a completely resected pheochromocytoma.Discussion: This case reflects an atypical presentation of pheochromocytoma; a disease with high cardiovascular morbidity and mortality [3, 4]. The case demonstrates that the absence of hypertension or all three symptoms of the “classic triad” does not exclude the diagnosis of pheochromocytoma and any singular symptom of catecholamine excess warrants an evaluation for pheochromocytoma. This case report helps to establish the need to better quantify individual symptoms of patients with this disease in order to better understand the entire spectrum. Providers need to be aware of atypical presentation of this disease in order to decrease poor outcomes that can result from undiagnosed pheochromocytoma. 1. Beard, C.M., Sheps, S.G., Kurland, L.T., Carney, J.A., Lie, J.T., Occurence of pheochromocytoma in Rochester, Minnesota 1950-1979. Mayo Clinic proceedings, 1983.2. Bravo, E.L., Pheochromocytoma: New concepts and future trends. Kidney International, 1991. 40.3. Lenders, J.W.M., Duh, Q.Y., Young, W.F, et. al, Journal of Clinical Endocrinology and Metabolism. 2014.4. Zelinka, T., Petrak, O., Turkova, H., et. al, High Incidence of Cardiovascular Complications in Pheochromocytoma. Hormone and Metabolic Research, 2012.

Development of a new electrochemical sensor based on modified carbon paste electrode for simultaneous determination of norepinephrine and acetaminophen in real samples

An electrochemical method has been described for the voltammetric oxidation and determination of norepinephrine (NE) at a carbon paste electrode (CPE) modified with RuO2 nano-roads and ionic liquid. The results indicated that the voltammetric response of norepinephrine was improved distinctly at the surface of modified electrode and the oxidation of norepinephrine at the surface of modified electrode occurs at a potential about 200 mV less positive than that of an unmodified CPE. The anodic peak was characterized and the process was diffusion-controlled. The current measured by differential pulse voltammetry (DPV) presented a good linear property as a function of the concentration of norepinephrine in the range of 0.07-400.0 µM, with a detection limit of 0.02 µM for norepinephrine. Also, this modified electrode was used for simultaneous determination of norepinephrine and acetaminophen. Finally, the proposed method was successfully applied to norepinephrine and acetaminophen determination in pharmaceutical samples and urine as real samples.

Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers.

Earlier, we reported that chronic exposure topesticides causes a reduction in the acetylcholinesterase activity andhematological and biochemical alterations in agriculture workers. In continuation withthat, the present study aimed to investigate the pesticide-induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory-II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO-A and MAO-B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, these changes were associated with a higher incidenceof depression in agricultural workers.