Effect of Binding to Plasma Proteins on the Interpretation of Plasma Cortisol Concentrations after Accidental Injury

1981 ◽  
Vol 61 (4) ◽  
pp. 399-405 ◽  
Author(s):  
R. N. Barton ◽  
B. J. Passingham
Keyword(s):  
Plasma Proteins ◽  
Plasma Cortisol ◽  
Equilibrium Dialysis ◽  
Cortisol Concentration ◽  
Multiple Equilibrium ◽  
Albumin Concentration ◽  
Trauma Patients ◽  
Accidental Injury ◽  
Total Cortisol ◽  
Free Cortisol

1. The binding of cortisol to plasma proteins has been studied by multiple equilibrium dialysis of plasma samples taken from 14 patients before treatment after moderate or severe accidental injury and 2–5, 6–12 and 14–25 days later. 2. The total plasma cortisol concentration was initially high, but fell by 6–12 days to stable values probably near the upper limit of normal. 3. The plasma albumin and total protein concentrations fell during the first few days after the injury, but the fall in albumin was proportionally the greater. Both were rising again at the end of the study period. The albumin concentration was positively correlated with an index of its binding to cortisol calculable from the dialysis data. 4. The concentration of corticosteroid-binding globulin (CBG) rose between weeks 1 and 2 after trauma, with no statistically significant change before or afterwards. 5. The changes in binding proteins after injury were relatively small and did not greatly alter the relationship between free and total cortisol concentrations in plasma. It is concluded that in most trauma patients changes in free cortisol, generally considered to be the active fraction in plasma, can be followed adequately by measuring the total cortisol concentration.

Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing

2015 ◽  
Vol 53 (9) ◽  
Author(s):  
Julie Brossaud ◽  
Blandine Gatta ◽  
Antoine Tabarin ◽  
Jean-Benoît Corcuff
Keyword(s):  
Intensive Care ◽  
Roc Curves ◽  
Serum Cortisol ◽  
Cortisol Concentration ◽  
University Hospital ◽  
Serum Free ◽  
Concentration Determination ◽  
Total Cortisol ◽  
Free Cortisol ◽  
Before And After

AbstractSerum cortisol is routinely quantified by immunoassays. In intensive care units serum free cortisol (FC) determination has been described as a better indicator of survival than total cortisol (TC). To estimate FC different methods are available including saliva sampling. We compared five methods to estimate FC, before and after an ACTH stimulating test in patients suspected of adrenal insufficiency.Serum and saliva was collected from 130 patients from the Endocrine Department of a university hospital before and after tetracosactide injection for TC determination. FC was estimated: after serum ultrafiltration, quadratic (Coolens’) or cubic (Dorin’s) equations, using TC/cortisol-binding globulin concentrations ratio or using cortisol concentration determination in saliva.FC concentrations obtained by different techniques were significantly correlated and Passing-Bablok regressions showed no deviation from linearity between salFC and filtFC or quadFC. Using the routine assumption that the patients were correctly diagnosed using a post-tetracosactide TC threshold of 550 nmol/L the FC methods generating the best ROC curves wereFC concentrations obtained by different techniques are significantly but not similarly correlated with TC. As,

Tracheal fluid in fetal lambs: spontaneous decrease prior to birth

1979 ◽  
Vol 47 (5) ◽  
pp. 985-989 ◽  
Author(s):  
J. A. Kitterman ◽  
P. L. Ballard ◽  
J. A. Clements ◽  
E. J. Mescher ◽  
W. H. Tooley
Keyword(s):  
Preterm Labor ◽  
Plasma Proteins ◽  
Plasma Cortisol ◽  
Cortisol Concentration ◽  
Blood Gas ◽  
Arterial Blood Gas ◽  
Plasma Cortisol Concentration ◽  
Arterial Blood ◽  
Arterial Ph ◽  
Ph Range

We studied tracheal fluid (TF) production in 14 fetal lambs: 6 controls, 6 receiving atropine on 1 or more of the last 7 days before birth, and 2 with bilateral section of the cervical vagosympathetic trunk. A cannula diverted all TF into an intrauterine bag; we collected TF intermittently and measured its volume. All ewes delivered spontaneously at 128-150 days' gestation. TF production decreased before birth in all fetuses except one control. TF production decreased before birth in all fetuses except one control. TF production did not correlate with fetal arterial blood gas tensions, hematocrit, or plasma proteins. In controls only, TF production correlated with fetal arterial pH (P less than 0.02); however, the pH range was small and the correlation has questionable physiological significance. For all fetuses, TF production during the 7 days before birth correlated inversely with the plasma cortisol concentration of 48 h previously (n = 36; r = -0.603; P less than 0.001). We conclude a) TF production in fetal lambs decreases before spontaneous term or preterm labor; b) this decrease is not affected by atropine or by section of the cervical vagosympathetic trunk; and c) the decrease in TF production may be related to increased secretion of cortisol.

scholarly journals The effect of social stress on adrenal axis activity in horses: the importance of monitoring corticosteroid-binding globulin capacity

1998 ◽  
Vol 157 (3) ◽  
pp. 425-432 ◽  
Author(s):  
SL Alexander ◽  
CH Irvine
Keyword(s):  
Social Stress ◽  
Plasma Cortisol ◽  
Binding Capacity ◽  
Plasma Concentrations ◽  
Social Instability ◽  
Total Cortisol ◽  
Adrenal Axis ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Cortisol Levels

Plasma cortisol is largely bound to corticosteroid-binding globulin (CBG), which regulates its bioavailability by restricting exit from capillaries. Levels of CBG may be altered by several factors including stress and this can influence the amount of cortisol reaching cells. This study investigated the effect of social instability on plasma concentrations of CBG, total and free (not protein bound) cortisol in horses. Horses new to our research herd ('newcomers') were confined in a small yard with four dominant resident horses for 3-4 h daily for 3-4 (n = 5) or 9-14 (n = 3) days. Jugular blood was collected in the mornings from newcomers before the period of stress began ('pre-stress'), and then before each day's stress. Residents were bled before stress on the first and thirteenth day. Residents always behaved aggressively towards newcomers. By the end of the stress period, all newcomers were subordinate to residents. In newcomers (n = 8) after 3-4 days of social stress, CBG binding capacity had fallen (P = 0.0025), while free cortisol concentrations had risen (P = 0.0016) from pre-stress values. In contrast, total cortisol did not change. In residents, CBG had decreased slightly but significantly (P = 0.0162) after 12 days of stress. Residents and newcomers did not differ in pre-stress CBG binding capacity, total or free cortisol concentrations. However, by the second week of stress, CBG binding capacity was lower (P = 0.015) and free cortisol higher (P = 0.030) in newcomers (n = 3) than in residents. Total cortisol did not differ between the groups. In conclusion social stress clearly affected the adrenal axis of subordinate newcomer horses, lowering the binding capacity of CBG and raising free cortisol concentrations. However, no effect of stress could be detected when only total cortisol was measured. Therefore, to assess adrenal axis status accurately in horses, it is essential to monitor the binding capacity of CBG and free cortisol concentrations in addition to total cortisol levels.

Failure of glucocorticoid feedback in males of a population of small marsupials (Antechinus swainsonii) during the period of mating

1986 ◽  
Vol 108 (1) ◽  
pp. 63-68 ◽  
Author(s):  
I. R. McDonald ◽  
A. K. Lee ◽  
K. A. Than ◽  
R. W. Martin
Keyword(s):  
Feedback Control ◽  
Plasma Cortisol ◽  
Natural Populations ◽  
Cortisol Concentration ◽  
Plasma Testosterone ◽  
Acth Secretion ◽  
Mating Activity ◽  
Mating Period ◽  
Free Cortisol ◽  
Dexamethasone Suppression

ABSTRACT In an investigation of the factors leading to the increase in the concentration of plasma free glucocorticoid, which results in immunosuppression and death after mating of all males in natural populations of a small shrew-like marsupial, the dusky antechinus (Antechinus swainsonii), the integrity of the glucocorticoid feedback control of the concentration of plasma cortisol was examined by use of dexamethasone-suppression tests. Injection of 0·2 mg dexamethasone/kg i.m. caused a marked fall in the concentration of plasma cortisol 17 h later, approximately 2 months and 2 weeks before the annual mating period in mid-July. However, the same dose had no significant effect on the increased concentration of plasma cortisol characteristic of the mid- to late July mating period. Injection of 100 i.u. ACTH/kg i.m. caused a significant increase in the concentration of plasma cortisol 6–7 h later on all occasions, indicating that the responsiveness of the adrenal cortex to ACTH did not change. Pretreatment with dexamethasone had no effect on the ACTH-stimulated cortisol concentration, ruling out a possible direct effect of dexamethasone on adrenocortical secretion in this species. Dexamethasone also reduced the concentration of plasma testosterone when the level was low, before the mating period, but not when the level was high, at the beginning of the mating period. It is concluded that, in association with a rapid increase in the concentration of plasma testosterone, an increase in aggression and intense mating activity, glucocorticoid feedback control of ACTH secretion is impaired. This contributes to the rapid and sustained rise in the concentration of plasma free cortisol to immunosuppressive levels. J. Endocr. (1986) 108, 63–68

scholarly journals SAT-738 Sources of Error in Estimation of Cortisol Half-Life Using Conventional, Single-Compartment Model: Bias Due to Variation in CBG Concentration

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jennifer Fuh ◽  
Frank Urban ◽  
Clifford Qualls ◽  
Richard I Dorin
Keyword(s):  
Half Life ◽  
Compartment Model ◽  
Cortisol Concentration ◽  
Predictor Variables ◽  
Healthy Controls ◽  
Descriptive Model ◽  
Total Cortisol ◽  
Single Compartment ◽  
Free Cortisol ◽  
Single Compartment Model

Abstract Most reports of cortisol half-life in the literature report a range of 90-130 min, which results are based on descriptive model that assumes mono-exponential decay of a single, total cortisol compartment. Free cortisol half-life has been similarly assessed using a descriptive single compartment model (1). However, the descriptive model is not physiologic in view of the rapid exchange between protein-bound and free cortisol compartments and evidence that metabolic elimination is restricted to the free cortisol compartment. In the present study, we sought to explore potential limitations of the descriptive, single-compartment model for cortisol elimination by assessing the influence of CBG concentration ([CBG]) on cortisol half-life estimates obtained using the descriptive model. We studied the influence of [CBG] and other variables on descriptive cortisol half-life using a Monte Carlo simulation of cortisol concentration decay curves developed using data from healthy controls (1). Total cortisol concentration ([TF]) curves were generated on the basis of 4 predictor variables: (i) [CBG], (ii) albumin concentration, (iii) [TF] at time zero following iv bolus (total cortisol at time 0, y-intercept), and (iv) free cortisol half-life central to a mechanistic (dynamic, 3-compartment) model (2). Simulations used a multivariable normal distribution and selected means, SDs, and correlation structure among these 4 variables in healthy controls. After generation of a series of cortisol decay curves (n=1000), half-lives for total and free cortisol were solved using the conventional (descriptive, single-compartment) model. The influence of predictor variables on conventional half-life estimates were assessed using standardized beta (STB) coefficients, which represent change in the SD of the outcome (numerator, i.e. total or free cortisol half-life obtained by descriptive model) for each SD change in a predictor (denominator) in a multivariable context (3). For total cortisol half-life (descriptive model) STBs were 0.91 ([CBG]), 0.73 (free cortisol half-life), -0.37 (y-intercept), and 0.04 ([albumin]) (all P<0.001). For free cortisol half-life (descriptive model), STBs were 0.98 ([CBG]), 0.73 (free cortisol half-life), -0.78 (y-intercept), and 0.11 [albumin]) (all P<0.001). We conclude that the conventional descriptive model for estimation of cortisol has significant limitations, including inaccuracy and systematic bias related to the influence of CBG concentration on half-life estimates. By inference, a similar bias confounds interpretation of the half-life obtained using conventional single-compartment model of other hormones associated with high-affinity serum binding proteins. References: (1) Perogamvros et al. Clin Endo 2011;74:30-36, (2) Keenan et al. Am J Physiol Endocrinol Metab 2004;287:E652-E661 (3) Dorin et al., J Endocrinol Soc 2017 July;1(7):945-56.

scholarly journals The effect of manipulating growth in sheep by diet or anabolic agents on plasma cortisol and muscle glucocorticoid receptors

1986 ◽  
Vol 56 (1) ◽  
pp. 289-304 ◽  
Author(s):  
P. M. Sharpe ◽  
P. J. Buttery ◽  
N. B. Haynes
Keyword(s):  
Skeletal Muscle ◽  
Plasma Cortisol ◽  
Glucocorticoid Receptors ◽  
Binding Capacity ◽  
Cortisol Concentration ◽  
The Other ◽  
Trenbolone Acetate ◽  
Relative Binding Affinity ◽  
Relative Binding ◽  
Free Cortisol

1. The cortisol status (total plasma cortisol concentration, free cortisol concentration, transcortin capacity) and the characteristics of skeletal muscle binding for cortisol and dexamethasone were examined in female lambs either implanted with Zeranol or trenbolone acetate or whose dietary intake was restricted.2. The skeletal muscle glucocorticoid receptor had a high affinity for the glucocorticoid triamcinolone (relative binding affinity 0.85) and cortisol (relative binding affinity 0.51) with virtually no affinity for trenbolone.3. Trenbolone acetate treatment reduced the binding capacity of sheep skeletal muscle for cortisol within 2 d of implantation. The other treatments had little effect except a small reduction in the animals where food intake was restricted. Similarly, binding capacity for dexamethasone was reduced by trenbolone acetate treatment but was not affected by the other treatments. This reduction in trenbolone acetate-treated animals is, at least in part, due to a reduction in glucocorticoid receptors.4. Transcortin capacity was elevated by Zeranol treatment but reduced with diet restriction or trenbolone treatment.5. No support for the suggestion of free cortisol concentration being important in the growth-promoting mechanism of trenbolone or Zeranol was obtained.6. Although insulin concentrations were not significantly altered by treatment (P > 0.05), when combining all the animals there was evidence of a negative correlation between total cortiso1: insulin vaue (P < 0.05) or free cortisol: insulin value and growth rate (P < 0.001). Free cortisol was negatively correlated to growth rate (P < 0.05) and transcortin capacity positively correlated (P < 0.01).

scholarly journals Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

2000 ◽  
Vol 165 (2) ◽  
pp. 527-532 ◽  
Author(s):  
N Picard-Hagen ◽  
V Gayrard ◽  
M Alvinerie ◽  
V Laroute ◽  
C Touron ◽  
...  
Keyword(s):  
Plasma Cortisol ◽  
Binding Capacity ◽  
Equilibrium Dialysis ◽  
Free Fraction ◽  
Biologically Active ◽  
Total Plasma ◽  
Neurodegenerative Process ◽  
Naturally Occurring ◽  
Free Cortisol ◽  
And Control

Naturally scrapie-affected ewes present a syndrome of hypercortisolism as evaluated by measuring total plasma cortisol concentrations. The objective of this study was to investigate the plasma protein binding of cortisol and to evaluate the concentration of the biologically active free fraction of cortisol in scrapie-affected ewes. Corticosteroid binding globulin (CBG) binding parameters were evaluated by equilibrium dialysis in 13 naturally scrapie-affected ewes and nine healthy ewes, during two periods of the clinical evolution of the disease. The hypercortisolism of the scrapie-affected ewes was confirmed by a significant increase of the plasma 20 beta-dihydrocortisol and cortisone concentrations, while total cortisol concentrations, obtained from an isolated sample, did not differ between scrapie-affected and control ewes. The scrapie diagnosis was confirmed by histopathology. The CBG maximal capacity (B(max)) was two times lower in scrapie-affected ewes than in healthy ewes (37+/-32 nM and 73+/-28 nM respectively). The dissociation constant K(d) (8.8+/-3.7 nM and 9.8+/-3.0 nM respectively) and the non-specific constant value of binding to albumin (1.13+/-0.18 and 1.14+/-0.23 respectively) did not differ significantly between diseased and control ewes. The significant increased concentrations of CBG-free cortisol (i.e. both albumin-bound and free cortisol fractions) in scrapie-affected ewes indicates that total plasma cortisol concentration is not an appropriate index of pituitary-adrenocortical hyperactivity. In conclusion, ewes with naturally occurring scrapie display a syndrome of hypercortisolism associated with a lower CBG binding capacity which leads to an overexposure of glucocorticoid-sensitive targets to CBG-free cortisol. The physiopathological consequences of this overexposure on the development of the neurodegenerative process in prion disease are discussed.

Danazol and its principal metabolites interfere with binding of testosterone, cortisol, and thyroxin by plasma proteins.

1982 ◽  
Vol 28 (4) ◽  
pp. 696-698 ◽  
Author(s):  
R V Haning ◽  
I H Carlson ◽  
J Cortes ◽  
W E Nolten ◽  
S Meier
Keyword(s):  
Protein Binding ◽  
Plasma Proteins ◽  
Competitive Inhibition ◽  
Free Testosterone ◽  
Competitive Binding ◽  
Total Testosterone ◽  
Binding Assays ◽  
Total Cortisol ◽  
Free Cortisol

Abstract Danazol and its three principal metabolites (2-hydroxy-methylethisterone, 2-hydroxymethyl-1,2-dehydroethisterone, and ethisterone) competitively displace cortisol and testosterone from plasma proteins. This effect is in addition to the reported inhibition of the production of testosterone-binding globulin and thyroxin-binding globulin. We saw no competitive inhibition of thyroxin binding. Concentrations of total testosterone, total cortisol, and total thyroxin were low, whereas percentages of free testosterone, free cortisol, and free thyroxin were abnormally high in women being treated with danazol. Values for testosterone, cortisol, and thyroxin in danazol-treated patients should therefore be appropriately corrected before interpretation. Protein-binding assays for testosterone or cortisol that involve testosterone- or cortisol-binding globulin may be invalid in danazol-treated subjects because of the competitive binding of danazol and its metabolites to these proteins.

scholarly journals A nonlabeled method to evaluate cortisol production rate by modeling plasma CBG-free cortisol disposition

2001 ◽  
Vol 281 (5) ◽  
pp. E946-E956 ◽  
Author(s):  
N. Picard-Hagen ◽  
V. Gayrard ◽  
M. Alvinerie ◽  
H. Smeyers ◽  
R. Ricou ◽  
...  
Keyword(s):  
Production Rate ◽  
Plasma Cortisol ◽  
Specific Binding ◽  
Equilibrium Dialysis ◽  
Total Plasma ◽  
Entry Rate ◽  
Free Cortisol ◽  
Corticosteroid Binding Globulin ◽  
Radioisotopic Method

This study aimed to develop a nonlabeled method for the measurement of cortisol production rate to evaluate adrenal function. The cortisol production rate determination requires that of cortisol clearance, which is not a parameter but a variable resulting from the saturable binding of cortisol to corticosteroid-binding globulin (CBG). Our method is based on evaluation of the plasma clearance of the CBG-free cortisol fraction. This parameter was evaluated from a pharmacokinetic model of total plasma cortisol disposition that takes into account specific binding of the corticoid to CBG in the plasma. We have shown that the CBG-free cortisol kinetics and CBG-binding parameters thus evaluated are not statistically different from those obtained by the radioisotopic method and equilibrium dialysis, suggesting that the plasma CBG-free cortisol clearance is independent of the total plasma cortisol concentrations and represents the actual parameter of cortisol elimination. We validated this modeling approach by using it to calculate the in vivo entry rate of cortisol mimicked by the perfusion of cortisol at a known rate.

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