Correlation between plasma catecholamines, weight, and diabetes in pheochromocytoma and paraganglioma

2021 ◽  
Author(s):  
Lauren N Krumeich ◽  
Andrew J Cucchiara ◽  
Katherine L Nathanson ◽  
Rachel R Kelz ◽  
Lauren Fishbein ◽  
...  
Keyword(s):  
Body Weight ◽  
Hemoglobin A1c ◽  
Recurrent Disease ◽  
Plasma Catecholamines ◽  
Plasma Norepinephrine ◽  
Continuous Variables ◽  
Academic Hospital ◽  
Linear Modeling ◽  
Mixed Effect ◽  
Secondary Outcomes

Abstract Context Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. Objective The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1C (HA1C). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. Design A retrospective cohort study was performed (1999–2020). Wilcoxon rank-sum tests compared non-parametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HA1C. The median study duration was 54.2 months (IQR: 19.0–95.1). Setting Tertiary academic hospital. Patients 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR: 45–67) and 56.4% (N=203) were female. Main outcome measures The primary and secondary outcomes were weight and HA1C, respectively. Results On multivariable MEM, norepinephrine (p<0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (p<0.0005) correlated when only metanephrines were included. In the surgical cohort (N=272), normetanephrine decreased postoperatively and was inversely associated with weight (p<0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (p<0.0005) directly correlated with HA1C. Conclusion Plasma norepinephrine and its metabolite directly correlate with HA1C and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HA1C despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.

Catecholamine-fuel interrelationships during exercise in fasting men

1980 ◽  
Vol 48 (1) ◽  
pp. 109-113 ◽  
Author(s):  
J. M. Pequignot ◽  
L. Peyrin ◽  
G. Peres
Keyword(s):  
Maximal Oxygen Consumption ◽  
Plasma Catecholamines ◽  
Plasma Free Fatty Acid ◽  
Work Load ◽  
Bicycle Ergometer ◽  
Plasma Norepinephrine ◽  
Plasma Catecholamine ◽  
Adrenergic Response ◽  
Response To Exercise

Adrenergic response to exercise and the relationships between plasma catecholamines and blood energetic substrates were studied in sedentary men after 15 h of fasting. Subjects pedaled a bicycle ergometer until exhaustion at a work load approximating 80% maximal oxygen consumption. Working ability was diminished by the fast (P less than 0.025). Resting plasma norepinephrine level was increased by fasting. During exercise plasma epinephrine (E) and norepinephrine (NE) concentrations were more elevated in fasting subjects than in fed subjects. Plasma catecholamine (CA) levels in fasting men correlated with blood glucose, blood lactate, and plasma glycerol concentrations. There was no significative correlation between CA and plasma free fatty acid (FFA) levels. The increased adrenergic activity in fasting subjects correlated with reduced endurance time. This study emphasizes the role of CA release, probably combined with other hormonal factors, in the mobilization of energy substrates during submaximal exercise.

scholarly journals 1174. Phase 2 STRIVE Clinical Trial of Rezafungin for Treatment of Candidemia and/or Invasive Candidiasis Demonstrates Consistent Trough Concentrations Across Diverse Patient Populations

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S612-S613
Author(s):  
Shawn Flanagan ◽  
Christopher M Rubino ◽  
Taylor Sandison
Keyword(s):  
Body Weight ◽  
Invasive Candidiasis ◽  
Fungal Infections ◽  
Standard Of Care ◽  
Geographic Region ◽  
Continuous Variables ◽  
Phase 2 ◽  
Double Blind ◽  
Wide Range ◽  
Diverse Patient Populations

Abstract Background Rezafungin is a novel echinocandin antifungal in development for treatment as well as prevention (prophylaxis) of invasive fungal infections. STRIVE (NCT02734862) is a global, randomized, double-blind, placebo-controlled, Phase 2 trial evaluating safety and efficacy of IV rezafungin once weekly (QWk) for treatment of candidemia and/or invasive candidiasis compared with standard-of-care (IV caspofungin once daily with optional oral stepdown). Here we report pharmacokinetic (PK) data from the completed STRIVE trial analyzed by patient demographics at baseline. Methods Rezafungin Day 8 trough (Cmin) concentrations from patients treated with rezafungin were summarized categorically by race (black or white), sex (male or female), and geographic region (North America [NA], or Europe [EU]), or plotted versus continuous variables of age, body weight, body mass index (BMI), and body surface area (BSA). As the first dose of rezafungin was 400 mg for all rezafungin-treated patients, data from both dose groups (Group 1: 400 mg QWk; Group 2: 400 mg in Week 1 followed by 200 mg QWk) were combined in this analysis. Results Rezafungin mean Cmin (SD) values were 1.8 (0.7) and 2.3 (1.2) in black and white patients, 1.9 (1.0) and 2.6 (1.2) in males and females, and 1.9 (0.6) and 2.4 (1.3) in patients from NA and EU. There were small differences in point estimates between the groups, but there was a great deal of overlap and the differences are not expected to be clinically meaningful (Figure). Similarly, no trends in Cmin values were observed across a range of ages (20-80 years), weights (~40-155 kg), BMI (~15-65 kg/m2), and BSA (~1.4-2.4 m2). Figure Conclusion No meaningful differences in rezafungin Cmin values were observed in patients grouped by sex, race, or geographic region, or across a wide range of patient factors, including age and body weight and size. These findings indicate that a single rezafungin dose regimen can be expected to provide consistent PK across diverse patient populations. Disclosures Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Christopher M. Rubino, PharMD, Institute for Clinical Pharmacodynamics, Inc. (Employee)Spero Therapeutics (Grant/Research Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)

Influnce of the beta-adrenergic agonist clenbuterol on plasma catecholamines and lymphocyte beta-receptors

1986 ◽  
Vol 1 (3) ◽  
pp. 234-236
Author(s):  
B. Bondy ◽  
M. Ackenheil ◽  
G. Laakmann ◽  
H.T. Munz
Keyword(s):  
Specific Binding ◽  
Plasma Catecholamines ◽  
Adrenergic System ◽  
Plasma Norepinephrine ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Beta Receptors ◽  
Β Receptor ◽  
Beta Adrenergic Agonist ◽  
The Brain

SummaryThe influence of subchronic application of the β-adrenergic agonist clenbuterol on plasma norepinephrine (NE), epinephrine (E) and β-receptors on lymphocytes was investigated in 8 male, healthy volunteers. Treatment with clenbuterol (0.04 mg/day) for 6 days induced significant reduction of β-receptor specific binding in 7 of the 8 subjects with a mean decrease of 40% (p < 0.01) with no changes in affinity. Concomitantly an increase in the plasma NE concentration was observed (mean 50%, p < 0.01), but no significant overall alteration of E concentration. Our results suggest that β-adrenergic agonists exercise a similar effect on the peripheral adrenergic system and on the adrenergic system in the brain.

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Plasma Catecholamines ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Prolonged Administration ◽  
Chronic Stimulation ◽  
Sustained Hypertension ◽  
Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

Altered plasma catecholamines and numbers of α- and β-adrenergic receptors in platelets and leucocytes in hyperthyroid patients normalized under antithyroid treatment

1985 ◽  
Vol 110 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Dieter Ratge ◽  
Sabine Hansel-Bessey ◽  
Hermann Wisser
Keyword(s):  
Dissociation Constants ◽  
Plasma Catecholamines ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Plasma Norepinephrine ◽  
Thyroid State ◽  
Antithyroid Treatment ◽  
Equilibrium Dissociation Constants ◽  
Equilibrium Dissociation ◽  
Hyperthyroid Patients

Abstract. We measured plasma catecholamines, α- and β-adrenoreceptor numbers and the accumulation of cyclic adenosine monophosphate (cAMP) in the unstimulated state and in response to 10 μmol/l (-) isoproterenol in blood cells from 29 euthyroid controls and from 18 patients with spontaneous hyperthyroidism. In the thyrotoxic patients plasma norepinephrine (1.14 ± 0.5 nmol/l) and epinephrine (0.3 ±0.14 nmol/l) were significantly decreased compared with plasma norepinephrine (1.87 ± 0.7 nmol) and epinephrine (0.41 ± 0.19 nmol/l) in the controls (P < 0.01 and P < 0.05, respectively) and the values obtained in subjects rendered euthyroid by antithyroid treatment (P < 0.001, respectively). α-adrenoceptor density in platelet membranes obtained from patients in the hyperthyroid state (114 ± 38 sites per cell) was significantly decreased when compared with controls (159 ± 48 sites per cell, P < 0.01) and the values from patients under effective antithyroid treatment (136 ± 35 sites per cell, P < 0.01). On the contrary, a significant increase in β-adrenoceptor density in mononuclear leucocyte (MNL) membranes was found in hyperthyroid patients (1751 ± 237 sites/cell) when compared with controls (1510 ± 351 sites/cell, P < 0.05) and the same patients following antithyroid treatment (1455 ± 260 sites/cell, P < 0.001). The equilibrium dissociation constants (KD) did not change in hyperthyroidism. Basal cAMP concentrations in MNL were higher in untreated thyrotoxicosis (45 ± 18 pmol/106 cells/10 min) than in patients in the euthyroid state (35 ± 9 pmol/106 cells/10 min, P < 0.05). Our data support the hypothesis that the balance of α- and β-adrenoceptors depends on the thyroid state. However, before the reputed catecholamine supersensitivity in hyperthyroid man can be accepted, the relationship between alterations in adrenoceptors and the biological responsiveness to catecholamines has to be demonstrated in different human tissues.

Resistive training increases fat-free mass and maintains RMR despite weight loss in postmenopausal women

1995 ◽  
Vol 79 (3) ◽  
pp. 818-823 ◽  
Author(s):  
A. S. Ryan ◽  
R. E. Pratley ◽  
D. Elahi ◽  
A. P. Goldberg
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Postmenopausal Women ◽  
Body Fat ◽  
Fat Mass ◽  
Management Program ◽  
Fat Free Mass ◽  
Percent Body Fat ◽  
Plasma Norepinephrine ◽  
Resistive Training

Percent body fat increases with age and is often accompanied by a loss in muscle mass, strength, and energy expenditure. The effects of 16 wk of resistive training (RT) alone or with weight loss (RTWL) on strength (isokinetic dynamometer), body composition (dual-energy X-ray absorptiometry), resting metabolic rate (RMR) (indirect calorimetry), and sympathetic nervous system activity (catecholamines) were examined in 15 postmenopausal women (50–69 yr). RT resulted in significant improvements in upper and lower body strength in both groups (P < 0.01). The nonobese women in the RT group (n = 8) did not change their body weight or fat mass with training. In the obese RTWL group (n = 7), body weight, fat mass, and percent body fat were significantly decreased (P < 0.001). Fat-free mass and RMR significantly increased with training in both groups combined (P < 0.05). There were no significant changes in resting arterialized plasma norepinephrine or epinephrine levels in either group with training. RT increases strength with and without weight loss. Furthermore, RT and RTWL increase fat-free mass and RMR and decrease percent fat in postmenopausal women. Thus, RT may be a valuable component of an integrated weight management program in postmenopausal women.

Abstract P022: Determinants of Energy Balance: Differences Related to Body Weight and Body Composition

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gregory A Hand ◽  
Robin P Shook ◽  
Jason R Jaggers ◽  
Amanda Paluch ◽  
Vivek K Prasad ◽  
...  
Keyword(s):  
Body Composition ◽  
Body Weight ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Positive Association ◽  
Linear Modeling ◽  
Obesity Epidemic ◽  
And Storage ◽  
Lean Group

Conversion, utilization and storage of energy in the regulation of energy balance is poorly understood. These misconceptions arise from confusion related to energy balance and its impact on body weight and composition, and can bias the interpretation of findings that are important for the development of policies addressing the obesity epidemic. PURPOSE: Our purpose was to examine the regulation of interactions between total daily energy intake (TDEI) and energy expenditure (TDEE) in healthy adults. METHODS: Adults not limited by gender, race or ethnicity (n=430; aged 21 to 40; BMI of 20 to 35) participated in a battery of physiological, anthropomorphic, behavioral and psychological measurements that are associated with energy balance regulation. The primary components of energy balance regulation (TDEI and TDEE) were measured by 3 random 24-hour dietary recalls and SenseWear accelerometry, respectively. Body composition was determined by dual x-ray absorptiometry (DXA). Absolute and relative resting metabolic rates (aRMR and rRMR) were determined through hooded indirect calorimetry. General linear modeling was used to examine the relationships of weight and body fatness with TDEI and macronutrient composition as well as the largest components of TDEE including aRMR, rRMR and physical activity energy expenditure (PAEE). In addition, data were compared between participants with a healthy body fat % (below 25; n=123) and obese (at or above 30%; n=241). RESULTS: All results were adjusted for age, gender and race. TDEE was positively associated (r=.47, p<.001) with TDEI. There was a positive association between aRMR (L/min) and weight (r=.743, p<.001). By contrast, rRMR (ml/kg/min) was inversely correlated with body weight (r= -.38; p<.001). TDEI was significantly higher in the lean group (2465±66 to 1878±42, p<.001) with no measureable differences in macronutrient percentages. The lean group had a higher TDEE and PAEE as compared to the obese group. CONCLUSIONS: There was a robust matching of TDEI and TDEE across weight and body composition ranges. Heavy people burned more calories than lighter people although the lighter individuals had a higher rRMR. The leaner group had a higher TDEI, reflecting a potential regulation based on the greater TDEE in this group. Further, the increased TDEE could be explained by the higher PAEE (approximately 500 kcal) in leaner individuals. These findings emphasize that energy expenditure is related to mass rather than body composition. The regulation of energy intake and body composition is multifactorial, with PAEE a significant determinant for energy storage. This study was funded through an unrestricted grant from The Coca-Cola Company.

Endurance run increases circulating IL-6 and IL-1ra but downregulates ex vivo TNF-alpha and IL-1 beta production

1995 ◽  
Vol 79 (5) ◽  
pp. 1497-1503 ◽  
Author(s):  
J. P. Drenth ◽  
S. H. Van Uum ◽  
M. Van Deuren ◽  
G. J. Pesman ◽  
J. Van der Ven-Jongekrijg ◽  
...  
Keyword(s):  
Vascular Resistance ◽  
Ex Vivo ◽  
Plasma Catecholamines ◽  
Plasma Norepinephrine ◽  
O2 Consumption ◽  
Esophageal Temperature ◽  
Trained Subjects ◽  
Norepinephrine Concentration ◽  
Fluid Losses ◽  
Cutaneous Vascular Resistance

This investigation determined the manner in which the cardiovascular system copes with the dehydration-induced reductions in cardiac output (Q) during prolonged exercise in the heat. On two separate occasions, seven endurance-trained subjects (maximal O2 consumption 4.70 +/- 0.41 l/min) cycled in the heat (35 degrees C) for 2 h, beginning at 62 +/- 2% maximal O2 consumption. During exercise, they randomly received either 0.2 liter of fluid and became dehydrated by 4.9 +/- 0.2% of their body weight [i.e., dehydration trial (DE)] or 3.6 +/- 0.4 liter of fluid and replaced 95% of fluid losses [i.e., euhydration trial (EU)]. During the 10- to 120-min period of EU, Q, mean arterial pressure (MAP), systemic vascular resistance (SVR), cutaneous vascular resistance (CVR), and plasma catecholamines did not change while esophageal temperature stabilized at 38.0 +/- 0.1 degrees C. Conversely, after 120 min of DE, Q and MAP were reduced 18 +/- 3 and 5 +/- 2%, respectively, compared with EU (P < 0.05). This was associated with a significantly higher SVR (17 +/- 6%) and plasma norepinephrine concentration (50 +/- 19%, P < 0.05). In addition, CVR was also significantly higher (126 +/- 16 vs. 102 +/- 6% of 20-min value; P < 0.05) during DE despite a 1.2 +/- 0.1 degrees C greater esophageal temperature (P < 0.05). In conclusion, significant reductions in Q are accompanied by significant increases in SVR and plasma norepinephrine and a slight although significant decline in MAP. The cutaneous circulation participates in this systemic vasoconstriction as indicated by increases in CVR despite significant hyperthermia.

Does sympathetic dysfunction occur before denervation in pure autonomic failure?

2018 ◽  
Vol 132 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Ling Guo ◽  
Murray D. Esler ◽  
Carolina Sari ◽  
Sarah Phillips ◽  
Elisabeth A. Lambert ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Autonomic Failure ◽  
Muscle Sympathetic Nerve Activity ◽  
Plasma Catecholamines ◽  
Sympathetic Nerves ◽  
Pure Autonomic Failure ◽  
Plasma Norepinephrine ◽  
Multiple Systems ◽  
Sympathetic Dysfunction ◽  
Forearm Vein

Pure autonomic failure (PAF) is a rare sporadic disorder characterized by autonomic failure in the absence of a movement disorder or dementia and is associated with very low plasma norepinephrine (NE) levels—suggesting widespread sympathetic denervation, however due to its rarity the pathology remains poorly elucidated. We sought to correlate clinical and neurochemical findings with sympathetic nerve protein abundances, accessed by way of a forearm vein biopsy, in patients with PAF and in healthy controls and patients with multiple systems atrophy (MSA) in whom sympathetic nerves are considered intact. The abundance of sympathetic nerve proteins, extracted from forearm vein biopsy specimens, in 11 patients with PAF, 8 patients with MSA and 9 age-matched healthy control participants was performed following a clinical evaluation and detailed evaluation of sympathetic nervous system function, which included head-up tilt (HUT) testing with measurement of plasma catecholamines and muscle sympathetic nerve activity (MSNA) in addition to haemodynamic assessment to confirm the clinical phenotype. PAF participants were found to have normal abundance of the NE transporter (NET) protein, together with very low levels of tyrosine hydroxylase (TH) (P<0.0001) and reduced vesicular monoamine transporter 2 (VMAT2) (P<0.05) protein expression compared with control and MSA participants. These findings were associated with a significantly higher ratio of plasma 3,4-dihydroxyphenylglycol (DHPG):NE in PAF participants when compared with controls (P<0.05). The finding of normal NET abundance in PAF suggests intact sympathetic nerves but with reduced NE synthesis. The finding of elevated plasma ratio of DHPG:NE and reduced VMAT2 in PAF indicates a shift towards intraneuronal NE metabolism over sequestration in sympathetic nerves and suggests that sympathetic dysfunction may occur ahead of denervation.

scholarly journals Plasma Catecholamines in Friedreich’s Ataxia Assayed using High Performance Liquid Chromatography with Electrochemical Detection

1982 ◽  
Vol 9 (2) ◽  
pp. 205-208 ◽  
Author(s):  
A.D. Merkel ◽  
A. Barbeau
Keyword(s):  
High Performance Liquid Chromatography ◽  
Electrochemical Detection ◽  
Present Method ◽  
High Performance ◽  
Plasma Catecholamines ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Assay Method ◽  
Plasma Norepinephrine ◽  
Routine Assay

ABSTRACT:Resting levels of plasma norepinephrine, epinephrine and dopamine were determined in 9 patients diagnosed as having Friedreich’s Ataxia using a relatively new assay method, HPLC with electrochemical detection. Levels of norepinephrine and dopamine were found to be significantly elevated in patients as compared to controls while epinephrine, though increased, was not significantly higher. These results confirm in most parts previous findings of Pasternak et al. of increased plasma catecholamines and demonstrate the sensitivity and utility of the present method for the routine assay of plasma catecholamines.

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