Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin

Coolens, J L; Baelen, Hugo Van; Heyns, Walter

doi:10.1016/0022-4731(87)90071-9

Cited by 274 publications

(250 citation statements)

References 26 publications

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“…9,21 The lower CBG concentration in sepsis is multifactorial because of decreased liver synthesis, proteolytic cleavage by neutrophil elastase, and less common genetic mutations. 8,9,23 Also during sepsis, CBG has low binding activity for serum cortisol.…”

Section: Discussionmentioning

confidence: 99%

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

Estrada‐Y‐Martin

Orlander

2011

Chest

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B alance between infl ammation and antiinfl ammation is essential for survival during severe infections. Initially, studies performed during the late 1980s and 1990s using high doses of corticosteroids for short periods of time in severe sepsis and septic shock did not improve survival; even more, it increased the risk of dying. [1][2][3][4] More recently, a new concept of "relative" adrenal insuffi ciency in sepsis or critical illness-related corticosteroid insuffi ciency has been coined, and there has been a renewed interest in adrenal function during sepsis. Research studies using smaller doses of corticosteroids for longer period of time (5-7 days) were tested. 5,6 In 2002, Annane et al 7 performed a randomized controlled trial using hydrocortisone and fl udrocortisone in patients with severe sepsis. They found that patients with less than expected response to adrenocorticotropic hormone (ACTH) stimulation test had better survival when corticosteroid therapy was used. A subsequent study (Corticosteroid Therapy of Septic Shock ) failed to demonstrate improvement in survival; however, patients were not treated with fl udrocortisone as in the Annane study. 6 All these studies have used total serum cortisol levels to evaluate adrenal function, even though it is well known that only the unbound or free cortisol is biologically active. Free or unbound serum cortisol may be higher than expected during sepsis because of decrease in cortisol-binding globulin (CBG) and albumin. Eighty Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean Ϯ SD age was 56.6 Ϯ 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplifi ed Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P , .0001). The correlation between free serum cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P , .0001). The mean Ϯ SD free serum cortisol level was 2.27 Ϯ 1.64 m g/dL. The mean Ϯ SD salivary cortisol level was 2.60 Ϯ 2.69 m g/dL. The mean Ϯ SD total serum cortisol level was 21.56 Ϯ 8.71 m g/dL. The mean Ϯ SD CBG level ...

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Section: Discussionmentioning

confidence: 99%

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

Estrada‐Y‐Martin

Orlander

2011

Chest

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“…Based on the binding characteristics of CBG, a calculation of free serum cortisol concentrations can be performed from the concentrations of total serum cortisol, CBG, and albumin, respectively (12,14). This approach has been used in a number of investigations, but important limitations have to be recognized: besides the immunoreactive concentration of CBG, individual variations in the tertiary structure of CBG can determine cortisol binding (15,16).…”

Section: Introductionmentioning

confidence: 99%

Free serum cortisol: quantification applying equilibrium dialysis or ultrafiltration and an automated immunoassay system

Vogeser

Möhnle

Briegel

2007

Clinical Chemical Laboratory Medicine

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Background: Quantification of bioactive, free serum cortisol concentrations can characterize adrenocortical function more appropriately compared to total serum cortisol measurement. Ultrafiltration or equilibrium dialysis of serum samples allow direct measurement of free serum cortisol concentrations but respective methods have poorly been validated so far. The aim of our study was to investigate the analytical performance of free serum cortisol measurement employing equilibrium dialysis and ultrafiltration. Methods: Two commercially available ultrafiltration devices and self-assembled dialysis cells, respectively, were studied. Cortisol was quantified in filtrate or dialysate using an automated immunoassay system. Using two serum pools, the inter-assay coefficient of variation was determined for the three methods and a method comparison was performed. Results: Inter-assay coefficients of variation (ns10) between 3.2% and 14.8% were observed in the imprecision study. Method comparison demonstrated close agreement between free serum cortisol results obtained by ultrafiltration and equilibrium dialysis, respectively (equilibrium dialysiss1.2=ultrafiltra-tionq3.9 nmol/L; rs0.99; ns35). Conclusions: Direct quantification of free serum cortisol after equilibrium dialysis or ultrafiltration of the samples offers acceptable reproducibility and results in close agreement can be obtained. Both methods can potentially be introduced into a routine laboratory setting. Clin Chem Lab Med 2007;45:521-5.

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“…Conclusive calculation of free serum cortisol concentrations taking into account the latter variables, however, is not generally applicable, since it leads to complex equations which have to be solved by numeric procedures for which no software is commercially available (11,19,22). Interestingly, calculations that incorporate the binding characteristics of CBG and cortisol -both in a simplified form (17) and by computer simulation (22) -predict a non-linear rise in bioactive free serum cortisol with increasing total serum cortisol concentrations, even at constant CBG concentrations and within the physiological range of circadian variation of cortisol concentrations; a simple "free cortisol index" (13,21) fails to display this and should not be used.…”

Section: Discussionmentioning

confidence: 99%

“…Free hormone determination after equilibrium dialysis without dilution may be regarded as the highest attainable standard for this purpose (20). In the less laborious (but more expensive) technique of ultracentrifugation (17,25), protein concentration on the filtration membranes with local volume compression effects can affect hormone binding. Dialysis with dilution by a large volume of dialysis buffer can potentially alter the physiological free-to-bound equilibrium since the distribution volume of cortisol is largely increased, whereas the sample volume remains unchanged.…”

Section: Discussionmentioning

confidence: 99%

Free Serum Cortisol during the Postoperative Acute Phase Response Determined by Equilibrium Dialysis Liquid Chromatography-Tandem Mass Spectrometry

Vogeser¹,

Groetzner²,

Küpper³

et al. 2003

Clinical Chemistry and Laboratory Medicine

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In severely ill patients low concentrations of the corticosteroid binding globulin are typically found; the aim of this study was to quantify directly free bioactive cortisol concentrations in the sera of postoperative cardiosurgical patients. Serum samples of 12 consecutive patients undergoing aortocoronary bypass surgery taken preoperatively and on the postoperative days 1 to 4 were analyzed. Total serum cortisol was quantified using liquid chromatography-tandem mass spectrometry with an on-line sample extraction system and tri-deuterated cortisol as the internal standard, and free serum cortisol was measured after over-night equilibrium dialysis. Whereas on the first postoperative day, the median total serum cortisol concentration was approximately two-fold increased compared to preoperative samples (preoperatively, 245 nmol/l (interquartile range (IQR) 203 -293 nmol/l); first postoperative day, 512 nmol/l (IQR 410 -611 nmol/l)), median dialyzable free cortisol concentration was almost seven-fold increased (preoperatively, 14.2 nmol/l (IQR 10.9 -20.7 nmol/l); first postoperative day, 98.3 nmol/l (IQR 81.3 -134 nmol/l)). On the fourth postoperative day, median free cortisol was still significantly increased compared to baseline sampling (p < 0.05), whereas median total cortisol was not. A median of 5.7% (IQR 5.4 -7.0%) of total cortisol was found as free cortisol on the preoperative day, 21.2% (IQR 18.9 -23.5%) on the first postoperative day and 10.5% (IQR 9.8 -14.0%) on the fourth postoperative day. It is concluded that during the postoperative period the freeto-bound ratio of cortisol is highly variable and that during the acute phase response direct quantification of free bioactive cortisol concentrations seems to be biologically more appropriate than the measurement of total cortisol concentrations. Clin Chem Lab Med 2003; 41(2):146 -151

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Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin

Cited by 274 publications

References 26 publications

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

Free serum cortisol: quantification applying equilibrium dialysis or ultrafiltration and an automated immunoassay system

Free Serum Cortisol during the Postoperative Acute Phase Response Determined by Equilibrium Dialysis Liquid Chromatography-Tandem Mass Spectrometry

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