High Catecholamine Research Articles

Capillary Refill Time as a Part of Routine Physical Examination in Critically Ill Patients Undergoing Vasoactive Therapy: A Prospective Study.

Background/Objectives: In critically ill patients, achieving a mean arterial pressure (MAP) of 65 mmHg is a recommended resuscitation goal to ensure proper tissue oxygenation. Unfortunately, some patients do not benefit from providing such a value, suggesting that other indices are needed for better hemodynamic assessment. Capillary refill time (CRT) has emerged as an established marker for peripheral perfusion and a therapeutic target in critical illness, but its relationship with other exponents of hypoperfusion during vasopressor support after resuscitation period still warrants further research. This study aimed to investigate whether in critically ill patients after initial resuscitation, CRT would provide information independent of other, readily accessible hemodynamic variables. Methods: Critically ill patients who were mechanically ventilated after the resuscitation period and receiving vasopressors were prospectively studied between December 2022 and June 2023. Vasopressor support was measured using norepinephrine equivalent doses (NEDs). CRT, MAP and NED were assessed simultaneously and analyzed using Spearman's rank correlation. Results: A total of 92 patients were included and 210 combined MAP-CRT-NED-Lactate records were obtained. There was no correlation between CRT and MAP (R = -0.1, p = 0.14) or lactate (R = 0.11, p = 0.13), but there was a positive weak correlation between CRT and NED (R = 0.25, p = 0.0005). In patients with hypotension, in 83% of cases (15/18), CRT was within normal range, despite different doses of catecholamines. When assessing patients with high catecholamine doses, in 58% cases (11/19), CRT was normal and MAP was usually above 65 mmHg. Conclusions: Capillary refill time provides additional hemodynamic information that is not highly related with the values of mean arterial pressure, lactate level and vasopressor doses. It could be incorporated into routine physical examination in critically ill patients who are beyond initial resuscitation.

Small conductance calcium-activated potassium channel contributes to stress induced endothelial dysfunctions

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction.Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study.Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (ISK1–3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of ISK1–3. H2O2 enhanced ISK1–3 and ET-1 production. Enhancing ISK1–3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways.The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.

Roles and Mechanisms of Dopamine Receptor Signaling in Catecholamine Excess Induced Endothelial Dysfunctions.

Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 μM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. Patch clamp, FACS, ELISA, PCR, western blot and immunostaining analyses were performed in the study. Epi enhanced small conductance calcium-activated potassium channel current (ISK1-3) without influencing the channel expression and the effect was attenuated by D1/D5 receptor blocker. D1/D5 agonists mimicked the Epi effect, suggesting involvement of D1/D5 receptors in Epi effects. The enhancement of ISK1-3 caused by D1/D5 activation involved roles of PKA, ROS and NADPH oxidases. Activation of D1/D5 and SK1-3 channels caused a hyperpolarization, reduced NO production and increased ROS production. The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.

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.

Association between excess catecholamine synthesis and polymorphic premature ventricular contraction

BackgroundThe reasons for the etiology of premature ventricular contractions (PVCs) are not specifically known. Many patients are resistant to medical treatment, and a factor that would predict response to medical treatment cannot be identified. This study aims to investigate if a high catecholamine level results in polymorphic PVC. MethodsThis study was obtained by prospective data registry analysis. A total of 100 patients, 50 from the PVC group, and 50 from the control group have been evaluated. The participants who were included in the patient group had a polymorphic PVC of 5% or more in their 24-h Holter evaluations. Metanephrine showing the level of adrenaline and normetanephrine, showing the level of noradrenaline levels have been measured from these urine samples. ResultThere was no difference between the two groups in terms of biochemical and essential characteristics. Normetanephrine level has been significantly higher in the PVC group compared to the control group (323.9 ± 208.9 μg to 129.25 ± 67.88 μg; p < 0.001). Similarly, metanephrine level has also been higher in the PVC group (124.75 ± 82.43 μg to 52.615 ± 36,54 μg; p < 0.001). A positive and moderate correlation has been identified between the number and ratio of PVC and the metanephrine and normetanephrine levels. ConclusionIn this study, we found that the catecholamine levels were higher in the polymorphic PVC group than in the healthy volunteers. Also, an increase in the number and rate of PVC has been observed as the catecholamine levels increased. Clinical Trial RegistrationUrine Levels of Metanephrine and Normetanephrine in Patients With Frequent PVC; ClinicalTrials.gov number NCT03447002

From Neurocardiology to Stroke-Heart Syndrome.

The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and describe the relation between the central autonomic system and cardiac function and it will be presented in this narrative review. The Stroke-Heart syndrome groups the entire spectrum of cardiac changes - clinical, ECG, echocardiographic, biological, morphological - that occur in the first 30 days from the onset of stroke, especially in the first days. Their presence significantly marks the evolution and prognosis of stroke. The damage resulted from hypothalamus-pituitary-adrenal axis activation and high catecholamine release (adrenergic storm) targets mainly the myocyte and the microcirculation.The Takotsubo syndrome and Stunned myocardium are distinct forms of neurogenic myocardial ischemia - with changes in ECG, parietal motility, and biological markers - usually reversible although evolution towards cardiac dysfunction is also possible. The concept of Stroke-Heart syndrome and the brain-heart correlation brought new scientific information regarding stress cardiomyopathy or neurogenic myocardial injury.

Multimodality Imaging of Cardiac Paragangliomas.

Paragangliomas are rare neuroendocrine tumors of extra-adrenal autonomic paraganglia origin. Paragangliomas rarely involve the heart, and they account for less than 1% of primary cardiac tumors. Most cardiac paragangliomas are incidentally detected at echocardiography or CT or during the workup of symptomatic patients with high catecholamine levels. Paragangliomas are typically located around the great vessels, coronary arteries (atrioventricular groove), or the atria, which can be explained by the tumor origin from the paraganglia and the distribution of the cardiac plexus. At MRI, cardiac paragangliomas typically have low to intermediate signal on T1-weighted images and high signal on T2-weighted images. The tumors are strongly vascularized, with high uptake on first-pass perfusion images and a heterogeneous pattern on late gadolinium enhancement images. Functional imaging is indicated for diagnostic confirmation and to screen for additional tumor locations or metastatic disease. Surgical excision is the only curative treatment. Cardiac CT angiography or invasive angiography should be performed preoperatively to precisely delineate tumor vascularization. In particular, its relation with the coronary arteries should be determined, as paragangliomas can be perfused by the coronary arteries, posing additional surgical challenges and the need for coronary revascularization. This imaging essay reviews the characteristics of paragangliomas and the use of multimodality imaging for diagnosis and treatment. Keywords: CT Angiography, Molecular Imaging, MR Imaging, PET/CT, Cardiac, Heart, Neoplasms-Primary © RSNA, 2023.

PE-452787-1 THE RELATIONSHIP BETWEEN VENTILATORY ANAEROBIC THRESHOLD AND ARRHYTHMIA ONSET IN PATIENTS WITH CATECHOLAMINERGIC VENTRICULAR TACHYCARDIA

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic disease associated with malignant ventricular arrhythmias, typically developing at high heart rate (HR) and catecholamine states. Patients are often restricted from exercise. Cardiopulmonary exercise testing (CPET) is used to diagnose and monitor patients to ensure HR-associated arrhythmias are adequately blunted on beta blockers (BB). In addition to peak HR, CPET can also determine the ventilatory anaerobic threshold (VAT), the point at which the body shifts from aerobic to anaerobic metabolism generating lactic acid as a byproduct. VAT is commonly used in prescribing exercise intensity in those with and without heart disease but has not been evaluated in CPVT patients. This transition point could be useful clinically in determining more precise exercise limits in patients with CPVT. To assess if there is an association between VAT and the development of arrhythmia during exercise in those diagnosed with CPVT. This is a retrospective cohort study on all patients with CPVT completing exercise testing at our institution from July 2017 through September 2022. VAT was calculated utilizing the V-slope method. Simple ectopy was defined as single, uniform premature ventricular complexes (PVCs) and complex ectopy defined as polymorphic PVCs or ventricular tachycardia. The HR at the time ventricular ectopy first developed was noted. There were 44 CPETs completed by 10 patients (19.8±10.4 years-old at first test; 50% male) with genetically-confirmed CPVT. Most tests occurred while the patient was on BB therapy (39/44). Patients had simple ectopy in 34 tests and complex ectopy in 25. No patients developed complex ectopy before VAT during any test (Figure 1). Average HR at VAT (101.4±14.7 bpm) was below both the HR at which simple (122.1±14.3 bpm) and complex (136.8±18.4 bpm) ectopy developed. Average HR at each point in exercise was lower in the group on BB than those not on a BB. These HR and arrhythmia trends were similar on the initial CPET at diagnosis and on their subsequent tests. Patients with CPVT seem to reach VAT prior to the onset of ventricular ectopy. Anaerobic metabolism may play a role in the arrhythmogenicity of these patients, possibly due to lactic acid production. If confirmed in larger studies, activity restrictions could be liberalized to allow low-intensity exercise below the VAT with precise HR goals in patients with CPVT.

MELD-score for risk stratification in cardiac surgery.

The outcome of the patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) is also influenced by the renal and hepatic organ functions. Risk stratification, using scores such as EURO Score II or STS Short-Term Risk Calculator for patients undergoing cardiac surgery with cardiopulmonary bypass, ignores the quantitative renal and hepatic function; therefore, MELD-Score was applied in these cases. We retrospectively examined patient data using the MELD score as a predictor of mortality. To perform a univariate analysis of the data, patients were classified into three groups based on the MELD Score: MELD < 10 (Group 1), MELD 10 to 19 (Group 2), and MELD ≥ 20 (Group 3). A total of 11,477 participants were included in the study, though several patients with either missing MELD scores or lack of creatinine, bilirubin, or INR levels were dropped from the original cohort. Eventually, 10,882 patients were included in the analysis. The primary outcome was defined as postoperative, in-hospital mortality. Secondary outcomes such as postoperative bleeding, including the requirement for repeat thoracotomy, postoperative neurological complications, and assessment of catecholamines on weaning from cardiopulmonary bypass/ requirement of mechanical circulatory support were examined. A higher MELD score was associated with increased postoperative mortality. Patients with MELD > 20 experienced a 31.2% postoperative mortality, compared to Group 1 (4.6%) and Group 2 (17.5%). The highest rates of postoperative bleeding (13.8%) and, repeat thoracotomy (13.2%) & postoperative pneumonia (17.4%) were seen in Group 3 (threefold increase when compared to Group 1, renal failure requiring dialysis (N = 235, 2.7% in Group 1 v/s N = 78, 22.9% in Group 3) or requiring high dose catecholamines post-operatively or mechanical circulatory support (IABP/ECLS). Incidentally, an increased MELD Score was not associated with a significant increase in the postoperative incidence of stroke/TIA or the presence of sternal wound infections/complications. A higher mortality was observed in patients with reduced liver and renal function, with a significant increase in patients with a MELD score > 20. As the current risk stratification scores do not consider this, we recommend applying the MELD score before considering patients for cardiac surgery.

Rapid-Onset Obesity with Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation Neuroendocrine Tumor Syndrome

Background: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) syndrome is a rare cause of obesity, characterized by early and rapid onset of obesity, hypoventilation, hypothalamic dysfunction, and autonomic dysfunction. When there is an associated neuroendocrine tumor, (NET) it becomes ROHHAD NET. Hypothalamic dysfunction causes endocrine problems, respiratory dysfunction, and autonomic alterations. It is difficult to distinguish this clinically from other obesity syndromes of genetic origin unless an individualized strategic approach is used. Clinical Description: We present a case of a 5-year-old developmentally normal girl with excessive weight gain starting in early childhood and the development of a squint. The clinical phenotype of central hypoventilation and autonomic dysfunction, central hypothyroidism, and central precocious puberty satisfied the criteria for ROHHAD syndrome. Management: A right-sided paraspinal supradiaphragmatic mass was identified that was excised and diagnosed as neuroblastoma on histopathology. Since there was no evidence of metastases, chemotherapy was not indicated. Alpha and beta-blockers were started for autonomic dysfunction and high catecholamine levels. Lack of improvement in behavioral manifestations prompted a trial of immunosuppressive therapy, but yielded no results. She ultimately succumbed to a probable cardiorespiratory arrest during sleep. Conclusions: ROHHAD syndrome should be considered a differential diagnosis in rapid-onset monogenic obesity and should be managed with a multidisciplinary approach. Prognosis is guarded due to sudden life-threatening events secondary to autonomic dysfunction.

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

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

The role of stress in the development of cardiovascular diseases

According to the American Heart Association, cardiovascular diseases are in the first place among the diseases that cause the most deaths in the world, responsible for 40,6% (95% confidence interval [CI] 24,5%-54,6%) of the world’s total deaths. There are many risk factors for CVD, including: smoking, alcohol, high blood pressure, high blood cholesterol, being physically inactive, obesity, diabetes and stress. It should be underlined that stress is taken into account less than others. The effect of chronic and acute stress on the occurrence of CVD is slightly different. Acute stress causes a high amount of catecholamines to be secreted in the blood. These hormones can cause many changes in the body, including tachycardia, high blood pressure, coronary vasoconstriction and/or stress cardiomyopathy. Stress cardiomyopathy, also known as Takotsubo syndrome (TTS) is an interesting side effect of acute stress, that causes changes in heart anatomy and physiology. Suddenly experienced strong emotional stress causes the left ventricle to change shape and resemble a balloon. The pathophysiology of the syndrome is not well understood, but many experts assume that high catecholamine levels can induce this pathology. Also, the condition is thought to be responsible for 2% of all acute coronary syndrome cases presenting to hospitals. Chronic stress affects cardiovascular system a little differently. According to a longitudinal and cohort study, constant stress increases risk of the heart attacks, angina and stroke. We know amygdala, an area of the brain that plays an important role in stress responses. When we experience constant stress, our amygdala sends signals to the bone marrow to produce more white blood cells, which then causes leukocytosis. This in turn causes the arteries to become inflamed and can lead to some cardiovascular and other problems like i mentioned before: Heart attacks, angina and stroke [1-4].

Abstract 13293: Albuterol and Hyperthyroidism as Potential Causes of Stress Cardiomyopathy

Introduction Takotsubo cardiomyopathy (TCM) is a recognized reversible process associated with emotional or physical stressors characterized by left ventricular apical ballooning in the absence of obstructive coronary artery disease. We present a unique case of TCM after albuterol use in the setting of hyperthyroidism. Results A 74-year-old woman with history of hyperthyroidism and asthma presented with acute substernal chest pain and progressive dyspnea. She was diagnosed with an asthma exacerbation, started oral prednisone 3 days before presentation, and reported using 16 puffs of her albuterol inhaler the day before. Examination revealed blood pressure 157/100 mmHg, heart rate 135 beats per minute, respiratory rate of 35 breaths per minute, and SpO2 94% on a 5-liter nasal cannula. Lung exam revealed bilateral end-expiratory wheezes, and she appeared in respiratory distress. The remainder of the exam was unremarkable, including cardiac exam. ECG revealed atrial tachycardia with ST elevations in the anterolateral leads concerning for injury. High sensitivity troponin was 1484 ng/L (ref &lt;19), free T4 level 3.63 ng/dL (ref 0.56-1.64 ng/dL), TSH &lt;0.02 μU/mL (ref 0.35-3.30 μU/mL ) with TSH-receptor Ab 8.62 IU/L (ref &lt;1.75 IU/L) consistent with worsening hyperthyroidism when compared to one month prior (free T4: 1.19 ng/dL; TSH: 0.84 μU/mL/mL). Emergent cardiac catheterization showed non-obstructive coronary artery disease and reduced ejection fraction (EF) of 30% with akinesia of the anterolateral, apical, and diaphragmatic segments consistent with TCM. She had a full recovery of systolic function noted on repeat echocardiogram 10 weeks after treatment with guideline-directed therapy. Conclusion TCM is primarily driven by a high catecholamine state that, paradoxically, increases β-2 adrenergic receptor inhibitory signaling, thus, causing preferential depression of apical myocardial function possibly due to topographic receptor distribution. Hyperthyroidism mimics a state of adrenergic excess partially mediated by the upregulation of β-adrenergic receptors by thyroid hormones, and the use of β-2 agonists potentiated the development of TCM.

PSUN15 Recurrence of Benign Pheochromocytoma

Abstract INTRODUCTION: Pheochromocytoma is a rare, usually benign, tumor of adrenal medulla. The prevalence is about 4.5-6.5%. The common presenting symptoms are headache, palpitations, diaphoresis, flushing, hypertension, and tachycardia. The high catecholamine levels can also result in arrhythmias, cardiomyopathy, stroke, and even death. It can also be asymptomatic and diagnosed as an adrenal incidentaloma on routine imaging. Due to its diverse and non-specific presentation, it is often called a great mimic in medicine. It is diagnosed both biochemically with plasma or urine metanephrines and by imaging (CT or MRI). The first line treatment is surgical resection of adrenal gland, adrenalectomy. Resected tumors should be pathologically confirmed for absence of malignancy. The recurrence of benign pheochromocytoma after adrenalectomy is rare. Recurrence rate following adrenalectomy is 6.5-16.5%. There are no identified predictors of recurrence but usually it occurs after 2-3 years. Annual imaging and biochemical testing for plasma and urinary metanephrines is recommended for early diagnosis of recurrence. CASE PRESENTATION: A middle aged female with past medical history of uncontrolled hypertension and uncontrolled diabetes mellitus underwent CT scan for abdominal pain, fatigue, and unintentional weight loss. She also complained of intermittent palpitations, chest heaviness, sweating, facial flushing, and headaches. Family history was negative for endocrinopathies or endocrine malignancies. CT showed 12 cm right adrenal mass. Plasma metanephrines were ordered given the imaging findings and they were elevated at more than 13000 pg/nl (normal &amp;lt; 60 pg/ml). All other adrenal hormones were within normal range. She was diagnosed with pheochromocytoma and underwent right adrenalectomy. The tumor was confirmed to be benign by histopathology. Post-surgery her symptoms resolved, and biochemical tests normalized with plasma metanephrine at 35 pg/ml. She presented again 4 years later with similar symptoms. Patient experienced palpitation and noted to have high blood pressure at home. She had also been experiencing flushing and having a sense of impending doom. On examination the patient was diaphoretic and review of systems was positive for heat intolerance, polydipsia and polyuria. EKG revealed sinus tachycardia and blood glucose was elevated. Labs revealed elevated plasma metanephrine and normetanephrine levels. Renin activity and plasma aldosterone levels were normal. CT scan confirmed soft tissue masses, 2. 0 x4. 0 cm posteriorly and 2. 0 x3.2cm laterally, in the pararenal space surrounding the right kidney, suggestive of local recurrence of pheochromocytoma. CONCLUSION: Even though rare, the recurrence of pheochromocytoma can occur, usually after 2-3 years. Annual imaging and biochemical testing is recommended to diagnose recurrent pheochromocytoma, especially in patients with large tumors (&amp;gt;5cm). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Importance of catecholamine signaling in the development of platelet exhaustion after traumatic injury

BackgroundImpaired ex vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remain incompletely understood, but functional platelet exhaustion due to excessive in vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex vivo platelet aggregation in trauma patients may be linked to catecholamine‐induced functional platelet exhaustion. ObjectiveTo determine the relationship of catecholamines with platelet‐dependent hemostasis after injury and to model catecholamine‐induced functional platelet exhaustion in healthy donor platelets. Patients/MethodsWhole blood was collected from 67 trauma patients as part of a prospective cohort study. Platelet aggregometry and rotational thromboelastometry were performed, and plasma epinephrine (EPI) and norepinephrine (NE) concentrations were measured. The effect of catecholamines on healthy donor platelets was examined in a microfluidic model, with platelet aggregometry, and by flow cytometry examining surface markers of platelet activation. ResultsIn trauma patients, EPI and NE were associated with impaired platelet aggregation (both p < 0.05), and EPI was additionally associated with decreased viscoelastic clot strength, increased fibrinolysis, and mortality (all p < 0.05). In healthy donors, short duration incubation with EPI enhanced platelet aggregation, platelet adhesion under flow, and increased glycoprotein IIb/IIIa activation, while weaker effects were observed with NE. Compared with short incubation, longer incubation with EPI resulted in decreased platelet adhesion, platelet aggregation, and surface expression of glycoprotein IIb/IIIa. ConclusionsThese findings suggest sympathoadrenal activation in trauma patients contributes to impaired ex vivo platelet aggregation, which mechanistically may be explained by a functionally exhausted platelet phenotype under prolonged exposure to high plasma catecholamine levels.

Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report

BackgroundEctopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases.Case presentationWe present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient’s death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-β-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation.ConclusionsWe experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.

The pleiotropic effects of melanin loss in cave snails Physella sp.

A traditional explanation for the loss of pigmentation in cave dwellers is the absence of negative selection acting on surface species to remove all albinos from the population. Recently, however, evidence has been accumulating that albinism in the cavefish Astyanax mexicanus has several beneficial pleiotropic effects. Albino cavefish have higher catecholamine levels due to a loss-of-function mutation in the oca2 gene, higher resistance to anesthesia, and sleep less than their pigmented, surface-dwelling conspecifics. All of these traits are beneficial to cavefish, given the scarcity of food and the availability of mates in caves. To understand whether pleiotropy might be a general mechanism for the loss of melanin pigmentation in cave animals, we use Physella sp., a freshwater snail from SW Illinois, USA. Within one cave Physella sp. occurs in several different morphs, ranging from completely albino to fully pigmented individuals. Using melanogenic substrate assay, we demonstrated that the first step of melanin synthesis is blocked in Physella sp. To investigate the pleiotropic effects of this blockade, we tested anesthesia resistance (AR). Similar to A. mexicanus, albino morphs of Physella sp. exhibited higher AR levels compared to pigmented morphs, with AR being controlled by the noradrenergic system in both morphs. AR and the noradrenergic system are linked to melanin synthesis via a common precursor L-tyrosine, which can be redirected between melanin and catecholamine pathways. Using RNA sequencing of albino and pigmented morphs of Physella sp. we aim to gain further insight into other pleiotropic effects of melanin loss. Our results suggest that pleiotropy may be involved in the evolution of albinism in both cave vertebrates and invertebrates.

Protective Effects of Sauropus Androgynus Leaf Extract against Isoproterenol Induced Cardiotoxicity.

The identification of cardioprotective effects of the ethanolic extract of Sauropus androgynus (EESA) leaves was performed using in vitro and in vivo models. The cell culture studies were performed using cardio myoblast cells (H9C2) and in vivo cardioprotective effects of EESA was assessed in albino wistar rats employing isoproterenol (ISO) as cardiotoxic agent. The animals were divided into six treatment groups and myocardial infraction was induced at 14th day followed by the treatment with therapeutic doses of EESA (100, 200 and 400mg/kg) for next two days. Various biochemical and histopathological parameters were evaluated in animals kept under control and treatment groups. The in vitro cell line studies revealed a positive impact on H9C2 cells. The ethanolic extract of Sauropus androgynus depicted low toxicity on cardiomyoblast cells and significant proliferation was observed after treatment. The results from animal studies have shown 1.7 times reduction in serum LDH (151.9 ± 1.302) and CPK (237.6 ± 5.781) levels with EESA treated groups compared to toxic control. EESA also significantly increased the antioxidant enzyme levels, which are responsible for cardioprotective effects in animals. This research study reveals that EESA possess antioxidant activity and also provides a protective role against myocardial infarction induced by ISO. We conclude that EESA could be a potential candidate to prevent and treat cardiotoxic consequences of high catecholamine levels.

Metabolic Response in Endothelial Cells to Catecholamine Stimulation Associated with Increased Vascular Permeability.

Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial function. The regulation of the endothelial cell metabolism is distinct and profoundly important to endothelium homeostasis. However, a precise catalogue of the metabolic alterations caused by sustained high catecholamine levels that results in endothelial dysfunction is still underexplored. Here, we uncover a set of up to 46 metabolites that exhibit a dose–response relationship to adrenaline-noradrenaline equimolar treatment. The identified metabolites align with the glutathione-ascorbate cycle and the nitric oxide biosynthesis pathway. Certain key metabolites, such as arginine and reduced glutathione, displayed a differential response to treatment in early (4 h) compared to late (24 h) stages of sustained stimulation, indicative of homeostatic metabolic feedback loops. Furthermore, we quantified an increase in the glucose consumption and aerobic respiration in endothelial cells upon catecholamine stimulation. Our results indicate that oxidative stress and nitric oxide metabolic pathways are downstream consequences of endothelial cell stimulation with sustained high levels of catecholamines. A precise understanding of the metabolic response in endothelial cells to pathological levels of catecholamines will facilitate the identification of more efficient clinical interventions in trauma patients.

Anaesthetic and Haemodynamic Effects of Dexmedetomidine vs Midazolam used as Premedication in Minor Obstetrics and Gynaecological ProceduresA Prospective Interventional Study

Introduction: Preoperative anxiety for any surgery is a frequent condition. It may lead to high catecholamine levels which increases blood pressure, heart rate and oxygen consumption. Various agents have been used for anxiolysis and sedation as premedicants. Aim: To compare the anaesthetic and haemodynamic effects of injection Dexmedetomidine and injection Midazolam used as premedication in minor Obstetrics and Gynaecological procedures. Materials and Methods: This was a prospective interventional study conducted from July 2016 to September 2017, on total number of 60 patients of American Society of Anaesthesiologist Physical Status (ASA PS I and II) enrolled for the study. They were randomised in two groups: Group A (n=30) for Injection (Inj.) Midazolam 0.04 mg/kg and Group B (n=30) for injection Dexmedetomidine 1mcg /kg injected over a period of 10 minutes prior to General Anaesthesia. After appropriate monitoring like, Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean arterial Pressure (MAP), Peripheral oxygen saturation (SpO2 ), Respiratory Rate (RR) were noted during the procedure at interval of 5 minutes till 30 minutes and, Ramsay Sedation Score (RSS) and Visual Analogue Scale (VAS) in postoperative period for 1 hour at interval of 15 minutes. The significance between all variables and amongst the two groups was calculated by Chi-square test, Repeated measure Analysis of Variance (ANOVA) test and Independent sample t test. Results: It was observed that mean HR, SBP (p&lt;0.05), DBP (p&lt;0.05) and MAP (p&lt;0.05 ) decreased significantly in group B. The RR (p&lt;0.05) was significantly decreased in group B. There was no significant difference in SpO2 (p=0.4) value in both the groups. VAS (p&lt;0.05) of group B patients was significantly reduced in the postoperative period but there was no significant difference in RSS score (p=0.1) at 45 and 60 minutes in both the groups. Conclusion: Dexmedetomidine is more effective as a sedative agent than injection Midazolam when used in minor gynaecological procedures. Though Dexmedetomidine caused significant reduction in SBP, DBP and HR, it maintained haemodynamic stability well without causing any adverse effects.