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Pheochromocytoma and paraganglioma: clinical feature-based disease probability in relation to catecholamine biochemistry and reason for disease suspicion.
Geroula, A, Deutschbein, T, Langton, K, Masjkur, J, Pamporaki, C, Peitzsch, M, Fliedner, S, Timmers, HJLM, Bornstein, SR, Beuschlein, F, et al
European journal of endocrinology. 2019;(4):409-420
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Abstract
OBJECTIVE Hypertension and symptoms of catecholamine excess are features of pheochromocytomas and paragangliomas (PPGLs). This prospective observational cohort study assessed whether differences in presenting features in patients tested for PPGLs might assist establishing likelihood of disease. DESIGN AND METHODS Patients were tested for PPGLs because of signs and symptoms, an incidental mass on imaging or routine surveillance due to previous history or hereditary risk. Patients with (n = 245) compared to without (n = 1820) PPGLs were identified on follow-up. Differences in presenting features were then examined to assess the probability of disease and relationships to catecholamine excess. RESULTS Hyperhidrosis, palpitations, pallor, tremor and nausea were 30-90% more prevalent (P < 0.001) among patients with than without PPGLs, whereas headache, flushing and other symptoms showed little or no differences. Although heart rates were higher (P < 0.0001) in patients with than without PPGLs, blood pressures were not higher and were positively correlated to BMI, which was lower (P < 0.0001) in patients with than without PPGLs. From these differences in clinical features, a score system was established that indicated a 5.8-fold higher probability of PPGLs in patients with high than low scores. Higher scores among patients with PPGLs were associated, independently of tumor size, with higher biochemical indices of catecholamine excess. CONCLUSIONS This study identifies a complex of five signs and symptoms combined with lower BMI and elevated heart rate as key features in patients with PPGLs. Prevalences of these features, which reflect variable tumoral catecholamine production, may be used to triage patients according to likelihood of disease.
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Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome
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Rubin, DA, Clark, SJ, Haqq, AM, Castner, DM, Ng, J, Judelson, DA
Hormone research in paediatrics. 2017;(3):153-161
Abstract
BACKGROUND Prader-Willi syndrome (PWS) is characterized by excessive adiposity. Excess adiposity negatively affects hormonal and metabolic responses to aerobic exercise. This study determined whether PWS and/or adiposity affected hormonal and metabolic responses to resistance exercise. METHODS Eleven children with PWS (11.4 ± 3.1 years, 43.9 ± 7.5% body fat), 12 lean children (9.3 ± 1.4 years, 18.3 ± 4.9% body fat), and 13 obese children (9.6 ± 1.3 years, 40.3 ± 5.2% body fat) participated. The children stepped onto an elevated platform while wearing a weighted vest for 6 sets of 10 repetitions per leg (sets separated by 1 min of rest). For the children with PWS, the platform height was 23.0 cm and vest load was computed as (20% of stature × 50% of lean body mass)/23.0 cm. For the controls, the platform height was 20% of the stature and vest load 50% of the lean body mass. Blood samples were obtained before, immediately after, and during recovery from exercise (+15, +30, and +60 min). RESULTS All groups had similar catecholamine, insulin, and glucagon responses. The groups showed no major differences in glucose and lactate levels. The PWS children demonstrated earlier increases in fatty acids during recovery and higher glycerol and ketone levels than the controls. CONCLUSION The PWS children demonstrated largely intact hormonal, glycolytic, and lipolytic responses to lower-body resistance exercise. In PWS, elevated ketone levels suggest an incomplete fat oxidation.
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Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation.
Christ, T, Rozmaritsa, N, Engel, A, Berk, E, Knaut, M, Metzner, K, Canteras, M, Ravens, U, Kaumann, A
Proceedings of the National Academy of Sciences of the United States of America. 2014;(30):11193-8
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Abstract
Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca(2+) releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca(2+)-current (ICa,L) responses, serotonin required and produced ∼ 100-fold less cAMP/PKA at the Ca(2+) channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF.
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Influence of high- and low-carbohydrate diet following glycogen-depleting exercise on heart rate variability and plasma catecholamines.
Lima-Silva, AE, Bertuzzi, R, Dalquano, E, Nogueira, M, Casarini, D, Kiss, MA, Ugrinowitsch, C, Pires, FO
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2010;(4):541-7
Abstract
The purpose of this study was to investigate the effects of a short-term low- or high-carbohydrate (CHO) diet consumed after exercise on sympathetic nervous system activity. Twelve healthy males underwent a progressive incremental test; a control measurement of plasma catecholamines and heart rate variability (HRV); an exercise protocol to reduce endogenous CHO stores; a low- or high-CHO diet (counterbalanced order) consumed for 2 days, beginning immediately after the exercise protocol; and a second resting plasma catecholamine and HRV measurement. The exercise and diet protocols and the second round of measurements were performed again after a 1-week washout period. The mean (+/-SD) values of the standard deviation of R-R intervals were similar between conditions (control, 899.0+/-146.1 ms; low-CHO diet, 876.8+/-115.8 ms; and high-CHO diet, 878.7+/-127.7 ms). The absolute high- and low-frequency (HF and LF, respectively) densities of the HRV power spectrum were also not different between conditions. However, normalized HF and LF (i.e., relative to the total power spectrum) were lower and higher, respectively, in the low-CHO diet than in the control diet (mean+/-SD, 17+/-9 normalized units (NU) and 83+/-9 NU vs. 27+/-11 NU and 73+/-17 NU, respectively; p<0.05). The LF/HF ratio was higher with the low-CHO diet than with the control diet (mean+/-SD, 7.2+/-6.2 and 4.2+/-3.2, respectively; p<0.05). The mean values of plasma catecholamines were not different between diets. These results suggest that the autonomic control of the heart rate was modified after a short-term low-CHO diet, but plasma catecholamine levels were not altered.
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Effects of electrical cervical spinal cord stimulation on cerebral blood perfusion, cerebrospinal fluid catecholamine levels, and oxidative stress in comatose patients.
Liu, JT, Tan, WC, Liao, WJ
Acta neurochirurgica. Supplement. 2008;:71-6
Abstract
OBJECTIVES Electrical spinal cord stimulation (SCS) is used to treat of chronic pain, obstructive arterial-related ischemia, and anginal pain. This study investigated cerebral blood perfusion, cerebrospinal fluid (CSF) catecholamine levels, and oxidative stress before and after cervical SCS in comatose patients. METHODS We evaluated cerebral blood perfusion, catecholamine (dopamine, norepinephrine, and epinephrine) levels, and oxidative stress in 20 comatose patients before and after SCS. After SCS for six months, cerebral blood perfusion (SPECT index, 2.293 +/- 0.255 vs. 2.779 +/- 0.209, p < 0.001), dopamine (49.0 +/- 12.1 vs. 198.9 +/- 62.6, p = 0.025), and norepinephrine (197.6 +/- 62.9 vs. 379.6 +/- 52.6, p = 0.021) but not epinephrine were significantly increased. Moreover, superoxide free radicals in whole blood were significantly decreased (210,079 +/- 47,763 vs. 109,212 +/- 20,086, p = 0.011) after SCS. Nine patients recovered from the consciousness within 71-287 days. CONCLUSIONS Increase of cerebral blood perfusion and catecholamines (dopamine and norepinephrine) in CSF after SCS was observed, whereas epinephrine level was unchanged. The superoxide free radicals were decreased after SCS. The results suggest that SCS increases cerebral blood perfusion, attenuates oxidative stress and increases biogenic amines in comatose patients.
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A correlation of catecholamine and vasoactive Peptide release with hemodynamics in patients undergoing resection of arteriovenous malformations.
Bloomfield, EL, Secic, M, Porembka, D
Neurocritical care. 2005;(2):127-31
Abstract
INTRODUCTION Control of blood pressure can be a problem for intracranial procedures. To investigate the relationship between hemodynamic variables and endogenous vasoactive substances, we studied patients undergoing resection of arteriovenous malformations (AVMs). METHODS This was a nonrandomized, prospective study of six patients who had resection of an intracranial AVM and six patients who had clipping of an intracranial aneurysm (ICA) that had not bled. Operative and postoperative blood pressure was controlled with sodium nitroprusside. Heart rate (HR), mean arterial pressure, pulmonary capillary wedge pressure, and cardiac index (CI) were measured after induction of anesthesia; before, during, and after hypotensive anesthesia; immediately postoperatively; and at 12, 24, and 36 hours postoperatively. Blood samples were drawn simultaneously in the AVM group to measure levels of norepinephrine, epinephrine, renin, aldosterone, vasopressin, angiotensin I, and angiotensin II and correlated with significant hemodynamic changes. RESULTS HR and CI increased significantly among patients with AVMs compared with patients with ICAs (p<0.001 and p=0.05, respectively). HR was significantly correlated with renin (r=0.60), norepinephrine (r=1.00), and vasopressin (r=0.66). CI was significantly correlated with epinephrine (r=1.00), renin (r=0.77), angiotensin II (r=0.71), and vasopressin (r=0.82). Patients with AVMs had a hyperdynamic state characterized by increases in HR and CI. These increases were accompanied by increased renin, norepinephrine, vasopressin, epinephrine, and angiotensin II serum concentrates. CONCLUSIONS There were no significant differences in blood pressure changes between patients who had resection for AVM and those who had clipping of ICA, probably due to the use of sodium nitroprusside in the AVM group. Patients with AVMs had a hyperdynamic state with increases in epinephrine, norepinephrine, angiotensin II, plasma renin activity, and vasopressin. Whether this hyperdynamic state is caused by the resection of the AVM or the use of sodium nitroprusside (SNP) cannot be concluded. Blockage of these mediators preoperatively may help control blood pressure without sodium nitroprusside.
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Hemodynamic and neurohumoral effects of selective endothelin A (ET(A)) receptor blockade in chronic heart failure: the Heart Failure ET(A) Receptor Blockade Trial (HEAT).
Lüscher, TF, Enseleit, F, Pacher, R, Mitrovic, V, Schulze, MR, Willenbrock, R, Dietz, R, Rousson, V, Hürlimann, D, Philipp, S, et al
Circulation. 2002;(21):2666-72
Abstract
BACKGROUND The endothelin (ET-1) system is activated in chronic heart failure (CHF). Whether, what type, and what degree of selective ET blockade is clinically beneficial is unknown. We investigated hemodynamic and neurohumoral effects of 3 weeks of treatment with various dosages of the orally available ET(A) antagonist darusentan in addition to modern standard therapy in patients with CHF. METHODS AND RESULTS A total of 157 patients with CHF (present or recent NYHA class III of at least 3 months duration), pulmonary capillary wedge pressure > or =12 mm Hg, and a cardiac index < or =2.6 L x min(-1) x m(-2) were randomly assigned to double-blind treatment with placebo or darusentan (30, 100, or 300 mg/d) in addition to standard therapy. Short-term administration of darusentan increased the cardiac index, but this did not reach statistical significance compared with placebo. The increase in cardiac index was significantly more pronounced after 3 weeks of treatment (P<0.0001 versus placebo). Pulmonary capillary wedge pressure, pulmonary arterial pressure, pulmonary vascular resistance, and right atrial pressure remained unchanged. Heart rate, mean artery pressure, and plasma catecholamines remained unaltered, but systemic vascular resistance decreased significantly (P=0.0001). Higher dosages were associated with a trend to more adverse events (including death), particularly early exacerbation of CHF without further benefit on hemodynamics compared with moderate dosages. CONCLUSIONS This study demonstrates for the first time in a large patient population that 3 weeks of selective ET(A) receptor blockade improves cardiac index in patients with CHF. However, long-term studies are needed to determine whether ET(A) blockade is beneficial in CHF.
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Effects of age, feeding regimen, and glucocorticoids on catecholamine and cortisol excretion in preterm infants.
Shulman, RJ, Heitkemper, M, O'Brian Smith, E, Lau, C, Schanler, RJ
JPEN. Journal of parenteral and enteral nutrition. 2001;(5):254-9
Abstract
BACKGROUND The sympathoadrenal system is important in maintaining normal physiologic functioning in infants and increased output also can reflect stress. We sought to determine the effects of age, feeding regimen, and glucocorticoids on catecholamine and cortisol excretion in preterm infants and to assess whether a particular strategy of feeding enhanced sympathoadrenal development or was stressful. METHODS Preterm infants (26-30 wk gestation; n = 171) were assigned randomly to begin trophic feedings from day 4 through 14 (trophic group) or to start feedings at day 15 (standard group) with feedings administered either by bolus every 3 hours (bolus) or continuously over 24 hours (continuous). At 10, 28, 40, 50, and 60 days of age, urine was collected continuously for 6 hours for measurement of catecholamines (norepinephrine, epinephrine, dopamine), cortisol, and creatinine. Data were available for 98 infants. RESULTS Norepinephrine excretion increased with postnatal age. The increase with age was significantly greater in the trophic group compared with that in the standard group. Epinephrine excretion did not change with age, and there were no differences between trophic and standard groups. Dopamine excretion increased with age but was similar between trophic and standard groups (borderline significantly greater in the trophic group). Cortisol excretion increased with age and also was similar between trophic and standard groups. There was no effect on catecholamine or cortisol excretion of bolus vs continuous feedings, antenatal or postnatal corticosteroids, gestational age at birth, age at which full feedings were attained, or use of human milk compared with preterm formula. CONCLUSIONS The greatest determinant of catecholamine and cortisol excretion is postnatal age. Feeding method, type of feeding, and glucocorticoid administration in the amounts customarily used have little significant effect on catecholamine or cortisol excretion. The apparent link between early feeding and norepinephrine (and possibly dopamine) excretion warrants further investigation.