High Catecholamine Levels Research Articles

Evolution of metabolic disorders after resection of pheochromocytomas and paragangliomas: a single-center study

Background and aims. Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, responsible for inappropriate secretion of catecholamines, inducing metabolic disorders, increasing basal metabolic rate. Our study aimed to analyze the metabolic profile pre- and post-operatively in patients undergoing surgery for pheochromocytomas and paragangliomas and additionally to determine the predictive factors of metabolic remission. Methods. This was a retrospective, unicentric, descriptive, and analytical study with a duration of 9 years. It includes data from 35 patients followed up for pheochromocytoma or paraganglioma in the Endocrinology-Diabetology and Nutrition Department of a University Hospital Center. All patients underwent surgery for pheochromocytoma or paraganglioma. Results. Among the 35 patients, 51.4% of the patients with pheochromocytomas had diabetes mellitus, and 42.8% had dyslipidemia. We found that high levels of catecholamines were associated with the onset of diabetes. We also noted that patients with a long history of the disease were statistically at greater risk of developing dyslipidemia. After surgery, the body mass index of our patients had statistically increased, and 50% of patients experienced resolution or improvement of their diabetes. Improvement of dyslipidemia was observed in 53% of patients. We also found that the percentage of dyslipidemia was higher in patients who did not resolve their diabetes. Conclusion. Diabetes mellitus and dyslipidemia are metabolic complications that must be investigated in patients with pheochromocytoma. Post-operative monitoring of body mass index and changes in glycemic and lipid levels is essential to adapt therapeutic management.

Catecholamine levels with use of electronic and combustible cigarettes.

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

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 μg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

A new perspective on cardiovascular function and dysfunction during endurance exercise: identifying the primary cause of cardiovascular risk.

Exercise mechanical efficiency typically falls within the range of approximately 20 to 25%. This means that a great part of the metabolic energy converted to generate movement is released as heat. Therefore, the rise in core temperature during endurance exercise in humans is proportional to generated work. Cutaneous vasodilation occurs when the core temperature threshold is reached. The rise in heart rate in response to thermal stress is a cardiovascular response that increases cardiac output and skin blood flow. The cardiovascular response during endurance exercise is a complex phenomenon potentially influenced by the involvement of nitric oxide in active thermoregulatory vasodilation. Excessive exercise can create high oxidative stress by disrupting the balance between free radicals' production and scavenging, resulting in impaired cardiovascular function. The above considerations are related to the severity and duration of endurance exercise. The first focus of this narrative review is to provide an updated understanding of cardiovascular function during endurance exercise. We aim to explore the potential role of oxidative stress in causing cardiovascular dysfunction during endurance exercise from a fresh perspective. Additionally, we aim to identify the primary factors contributing to cardiovascular risk during strenuous prolonged exercise by highlighting recent progress in this area, which may shed light on previously unexplained physiological responses. To ascertain the effect of endurance exercise on cardiovascular function and dysfunction, a narrative review of the literature was undertaken using PubMed, ScienceDirect, Medline, Google Scholar, and Scopus. The review highlighted that high oxidative stress (due to high levels of catecholamines, shear stress, immune system activation, and renal dysfunction) leads to a rise in platelet aggregation during endurance exercise. Importantly, we clearly revealed for the first time that endothelial damage, vasoconstriction, and blood coagulation (inducing thrombosis) are potentially the primary factors of cardiovascular dysfunction and myocardial infarction during and/or following endurance exercise.

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

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.

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.

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].

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.

Pathophysiology of stress cardiomyopathy: A comprehensive literature review.

IntroductionTakotsubo cardiomyopathy is a transient type of acute heart failure with distinct wall motion abnormalities and unclear pathophysiology. This review focuses on the proposed pathophysiological mechanisms that could be involved in the occurrence takotsubo cardiomyopathy.Main bodyAcute stress and subsequent excessive activation of the sympathetic nervous system are major factors in the pathophysiology of takotsubo cardiomyopathy. The high levels of catecholamine work in a triggering manner, generate reactive oxygen species, release inflammatory cytokines, and induce endothelial injury. The incidence of Takotsubo cardiomyopathy has increased following COVID-19 infection and vaccination, which suggests that neurohormonal and psychological factors (i.e., fear and anxiety of infection or vaccination) may have an additional role in the pathophysiology. In addition, inflammatory state, cytokine storm, augmented sympathetic activity, and endothelial dysfunction during the acute phase of COVID-19 infection may participate in Takotsubo cardiomyopathy. Chronic stress is also linked to this complex mechanism by accelerating cripple of endocrinal hypothalamic-pituitary-adrenal axis activity, which influences the cortisol effect on releasing catecholamine, which is directly related to the pathogenesis of takotsubo cardiomyopathy.ConclusionThe excessive activation of the sympathetic nervous system and subsequent high levels of catecholamines could initiate the process. The catecholamines, in turn, generate reactive oxygen species and release inflammatory cytokines (i.e., IL-1, IL-2, IL-6, IL-7, IL-8, CXCL1, TNF-α, and IFN-γ), which causes endothelial injury.

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.

Undifferentiated pleomorphic sarcoma of the retroperitoneum mimicking a cortisol‐ and catecholamine‐secreting adrenal tumor

IntroductionRetroperitoneal tumors with endocrine abnormalities are suspected to be functional adrenal tumors. Retroperitoneal soft tissue sarcomas are rare tumors, without endocrine potential.Case presentationA 60‐year‐old male was referred for a 15 cm mass in the left suprarenal space. His plasma cortisol and catecholamine levels were elevated. He underwent open left adrenalectomy with radical nephrectomy and his endocrinological abnormalities were improved. Pathological findings suggested that it had originated from the retroperitoneal fat tissue, and a diagnosis of undifferentiated pleomorphic sarcoma was made based on the results of immunohistochemical analysis and fluorescence in situ hybridization. Interestingly, neither cortisol nor catecholamine was elevated when, 6 months after surgery, local recurrence developed.ConclusionThis is the first reported case of undifferentiated pleomorphic sarcoma accompanied by high levels of cortisol and catecholamine. We should keep in mind the possibility of tumors like retroperitoneal soft tissue sarcomas inducing endocrine abnormalities.

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.

Abstract 13411: Vasodilatory Capacity With Regadenoson Myocardial Perfusion Imaging In Patients With End Stage Liver Disease

Introduction: The sensitivity and specificity of myocardial perfusion imaging in end stage liver disease (ESLD) patients ranges between 35-37% and 63-88%, respectively. Despite high levels of endogenous catecholamines and angiotensin, ESLD induced arterial vasodilation may exhaust the vasodilatory capacity of common pharmacologic stress agents. Reduced heart rate (HR) response to vasodilator stress test has been associated with increased major adverse cardiac events (MACE) in pre-transplant end stage renal disease patients but there is limited data in ESLD. We hypothesize that the hemodynamic response, measured as a change in HR and systolic blood pressure (SBP), during regadenoson stress test will be more robust when associated with low level exercise. Method: Forty-five subjects with ESLD referred for pre-transplant risk stratification were assigned to 1 of 3 groups: regadenoson alone or associated with low level treadmill or bicycle maneuver. Regadenoson was injected 2 minutes after low level exercise in the treadmill and bicycle groups. Myocardial perfusion images and hemodynamic changes were performed and interpreted as part of the standard clinical protocol. Results: There were 21 subjects in the regadenoson alone group, 10 in the low level treadmill group, and 14 in the bicycle maneuver group. There were no perfusion abnormalities in any of the groups and LVEF were greater than 50%. There was a statistically significant difference in HR response between the 3 groups (p = 0.015), but not in percentage SBP change between the 3 groups (p = 0.4). Pairwise comparison of regadenoson alone vs. low level treadmill percentage HR change showed statistical significance (p = 0.011). There was no MACE at 6-month follow-up. Conclusions: Low level exercise achieved a higher HR response than the other groups with a similar SBP response. The increased HR response may represent a more physiologic assessment of the true vasodilatory capacity remaining in ESLD patients.

Choline or CDP-choline restores hypotension and improves myocardial and respiratory functions in dogs with experimentally – Induced endotoxic shock

Endotoxin shock is associated with severe impairments in cardiovascular and respiratory functions. We showed previously that choline or cytidine-5′-diphosphocholine (CDP-choline) provides beneficial effects in experimental endotoxin shock in dogs. The objective of the present study was to determine the effects of choline or CDP-choline on endotoxin-induced cardiovascular and respiratory dysfunctions.Dogs were treated intravenously (i.v.) with saline or endotoxin (LPS, 0.1 mg/kg) 5 min before i.v. infusion of saline, choline (20 mg/kg) or CDP-choline (70 mg/kg). Blood pressure, cardiac rate, myocardial and left ventricular functions, respiratory rate, blood gases, serum electrolytes and cardiac injury markers were determined before and at 0.5-48 h after endotoxin. Plasma tumor necrosis factor alpha (TNF-α), high mobility group box-1 (HMGB1), catecholamine and nitric oxide (NO) levels were measured 2 h and 24 h after the treatments.Endotoxin caused immediate and sustained reductions in blood pressure, cardiac output, pO2 and pH; changes in left ventricular functions, structure and volume parameters; and elevations in heart rate, respiratory rate, pCO2 and serum electrolytes (Na, K, Cl, Ca and P). Endotoxin also resulted in elevations in blood levels of cardiac injury markers, TNF-α, HMGB1, catecholamine and NO. In choline- or CDP-choline-treated dogs, all endotoxin effects were much smaller in magnitude and shorter in duration than observed values in controls.These data show that treatment with choline or CDP-choline improves functions of cardiovascular and respiratory systems in experimental endotoxemia and suggest that they may be useful in treatment of endotoxin shock in clinical setting.

Left ventricular depression and pulmonary edema in rats after short-term normobaric hypoxia: effects of adrenergic blockade and reduced fluid load

Acute normobaric hypoxia may induce pulmonary injury with edema (PE) and inflammation. Hypoxia is accompanied by sympathetic activation. As both acute hypoxia and high plasma catecholamine levels may elicit PE, we had originally expected that adrenergic blockade may attenuate the severity of hypoxic pulmonary injury. In particular, we investigated whether administration of drugs with reduced fluid load would be beneficial with respect to both cardiocirculatory and pulmonary functions in acute hypoxia. Rats were exposed to normobaric hypoxia (10% O2) over 1.5 or 6 h and received 0.9% NaCl or adrenergic blockers either as infusion (1 ml/h, increased fluid load) or injection (0.5 ml, reduced fluid load). Control animals were kept in normoxia and received infusions or injections of 0.9% NaCl. After 6 h of hypoxia, LV inotropic function was maintained with NaCl injection but decreased significantly with NaCl infusion. Adrenergic blockade induced a similar LV depression when fluid load was low, but did not further deteriorate LV depression after 6 h of infusion. Reduced fluid load also attenuated pulmonary injury after 6 h of hypoxia. This might be due to an effective fluid drainage into the pleural space. Adrenergic blockade could not prevent PE. In general, increased fluid load and impaired LV inotropic function promote the development of PE in acute hypoxia. The main physiologic conclusion from this study is that fluid reduction under hypoxic conditions has a protective effect on cardiopulmonary function. Consequently, appropriate fluid management has particular importance to subjects in hypoxic conditions.