Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin

Lewis, John G.; Bagley, Christopher J.; Elder, Peter A.; Bachmann, Anthony W.; Torpy, David J.

doi:10.1016/j.cccn.2005.03.044

Cited by 180 publications

(139 citation statements)

References 10 publications

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“…Furthermore, no difference in pre-versus post-Synacthen CBG concentrations was found across the whole patient group (51 [11] mg/L versus 50 [13] mg/L, P ¼ 0.86), although variation in CBG between the two time points was observed in individual patients. The range of CBG concentrations measured in the group was noted to be wide (28-85 mg/L) when compared with the reference range quoted by the assay manufacturer (31-53 mg/L) (Biosource Europe, Nivelles, Belgium).…”

Section: Cbg Concentrationsmentioning

confidence: 81%

An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Barlow¹,

Holme

Stockley

et al. 2010

Ann Clin Biochem

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Background: Since more than 90% of cortisol is bound to protein, serum free cortisol (SFC) may be a more appropriate marker of adrenal status than total cortisol. However, measurement of SFC is technically difficult and calculated SFC may offer a more practical alternative. Methods: SFC, measured by equilibrium dialysis coupled with immunoassay, and calculated using Coolens' equation from total cortisol and corticosteroid binding globulin (CBG) concentrations, was compared in short Synacthen test (SST) serum from 42 patients, of whom 20 demonstrated a suppressed adrenal response. Results: Considering the patient group as a whole, calculated SFC was found to be significantly lower than measured SFC, pre-and post-Synacthen (P , 0.05 and ,0.001, respectively). Upon classifying the patients as pass or fail based on total cortisol response to Synacthen, the difference in calculated and measured SFC only reached statistical significance for postSynacthen concentrations in the pass group (P , 0.01), suggesting a greater discrepancy at higher cortisol concentrations. There was no difference in CBG levels between the pass and fail groups and both measured and calculated SFC gave a diminished 30 min response in subjects deemed to have failed the SST. Conclusion: Coolens' equation was found to underestimate measured SFC in this cohort of outpatients, as has been previously demonstrated, particularly in patients with a pronounced acute phase response. Although calculated SFC gave a diminished response in individuals deemed to have failed the SST, the concentration-dependent nature of the discrepancy may limit the usefulness of this method for assessing adrenal status.

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Section: Cbg Concentrationsmentioning

confidence: 81%

An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Barlow¹,

Holme

Stockley

et al. 2010

Ann Clin Biochem

View full text Add to dashboard Cite

show abstract

“…Most serum cortisol is bound to proteins, including corticosteroid-binding globulin and serum albumin (Perogamvros et al, 2011a,b), with both free and total concentrations varying diurnally. Free concentrations are between 10 and 300 nM (Lewis et al, 2005;Levine et al, 2007). Free cortisol passes easily through cellular membranes into the cytosol, where it can be converted to the inactive form-cortisone-or bind to intracellular cortisol receptors and reach the nucleus (Fig.…”

Section: Introductionmentioning

confidence: 99%

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

et al. 2015

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Endotoxin lipopolysaccharide (LPS) is known to cause liver injury primarily involving inflammatory cells such as Kupffer cells, but few in vitro culture models are applicable for investigation of inflammatory effects on drug metabolism. We have developed a threedimensional human microphysiological hepatocyte-Kupffer cell coculture system and evaluated the anti-inflammatory effect of glucocorticoids on liver cultures. LPS was introduced to the cultures to elicit an inflammatory response and was assessed by the release of proinflammatory cytokines, interleukin 6 and tumor necrosis factor a. A sensitive and specific reversed-phase-ultra high-performance liquid chromatography-quadrupole time of flightmass spectrometry method was used to evaluate hydrocortisone disappearance and metabolism at near physiologic levels. For this, the systems were dosed with 100 nM hydrocortisone and circulated for 2 days; hydrocortisone was depleted to approximately 30 nM, with first-order kinetics. Phase I metabolites, including tetrahydrocortisone and dihydrocortisol, accounted for 8-10% of the loss, and 45-52% consisted of phase II metabolites, including glucuronides of tetrahydrocortisol and tetrahydrocortisone. Pharmacokinetic parameters, i.e., half-life, rate of elimination, clearance, and area under the curve, were 23.03 hours, 0.03 hour 21 , 6.6 3 10 25 l×hour 21, and 1.03 (mg/l)*h, respectively. The ability of the bioreactor to predict the in vivo clearance of hydrocortisone was characterized, and the obtained intrinsic clearance values correlated with human data. This system offers a physiologically relevant tool for investigating hepatic function in an inflamed liver.

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“…Cortisol is commonly reported both as total cortisol and free cortisol. It is known that cortisol exists in plasma in three forms, 80-90% bound with high affinity to CBG, about 10-14 % associated with albumin and about 6-10% in unbound form as free cortisol [8,9,10,12,23,26,34,39,42]and it is suggested that only the free cortisol is biological active [8,10,12,36,42].There are several techniques for measurements and calculations of free cortisol but many of them are not suitable for routine laboratory use [5,11,12,15,17,43]. In this study we used a modified model (cortisol/CBG ratio) of the Free Cortisol Index [5].In our study we found no seasonal variations in the calculated cortisol-to-CBG ratio neither in OC users nor in non-users.…”

Section: Limitations and Methodological Aspectsmentioning

confidence: 99%

Physiology of Blood Components in Wound Healing: an Appreciation of Cellular Co-Operativity in Platelet Rich Plasma Action

Parrish¹

2017

JESO

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Open Access Research Articletraining sessions and periods, [19,30,31]and the time needed for recovery is considered to be much longer compared to OR [22]. Because of both gradual onset of OR and gradual transition from OR to OTS, it is important to detect symptoms at an early stage [30].No single, specific, and reliable biological parameter to diagnose OR and OTS at an early stage has been found, and there has been only little improvement in recent years in developing tools suitable for diagnostics [1,22,30,45]. Hence, physicians and trainers are looking for new ways to diagnose and monitor athletes that may be at risk [1,28].The resting cortisol level has been suggested to play an interesting role in detecting OR and OTS since it is thought to indicate stress [19,31]. However, levels of resting cortisol has been both increased, decreased and unchanged in over trained athletes, and the research has mainly been performed on male athletes [3,18,25,32,33,44,46].Female athletes have become a common part of the sports environment [21]and since most research has been performed on male athletes, studies on female athletes are warranted. Oral Contraceptive (OC) use is prevalent in female athletes [21,41] and the impact of OC use and non-use on cortisol levels in female athletes are not well studied. Hence the influence of both the exogenous and the endogenous hormonal profiles on athletic performance should be investigated [41]. An administration of estrogen, as in women with OC use, can cause increase in total plasma cortisol [8,10], and in free cortisol [39]. Coolens et al. [12] showed elevated cortisol levels in estrogen treated women, but unbound cortisol levels were similar to the control group. Since estrogen could influence cortisol levels, studies on female athletes should include both OC users and nonusers. Moreover, since seasonal periodicity in various endocrine functions can occur [24,37] it seems crucial to determine if this may effect cortisol levels differently in OC users and non-users. As the role of cortisol in indicating stress is multifaceted and complex there is a need to investigate both seasonal variation and impact of oral contraceptive use on cortisol levels to evaluate if cortisol could be used to diagnose and monitor female athletes that may be at risk to develop OR and OTS. AbstractWhen athletes optimize their physical performance, an imbalance could occur between the strain of training, time for recovery and the athlete's individual tolerance of stress that could lead to overreaching and overtraining syndrome. Cortisol has been suggested to be a biological, diagnostic marker to detect overreaching and overtraining syndrome, since it is thought to indicate stress. This study aimed to provide normative data on cortisol levels, hence investigate seasonality and impact of oral contraceptive use to elucidate if cortisol could be used as a diagnostic marker to detect overreaching and overtraining syndrome in female athletes. The women, divided in two groups, oral contraceptive users (n = 15) and ...

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Plasma free cortisol fraction reflects levels of functioning corticosteroid-binding globulin

Cited by 180 publications

References 10 publications

An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

An evaluation of measured and calculated serum free cortisol in a group of patients with known adrenal suppression

Metabolite Profiling and Pharmacokinetic Evaluation of Hydrocortisone in a Perfused Three-Dimensional Human Liver Bioreactor

Physiology of Blood Components in Wound Healing: an Appreciation of Cellular Co-Operativity in Platelet Rich Plasma Action

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