Assay of Unbound Cortisol in Plasma*

Robin, Philippe; Predine, J; Milgröm, Edwin

doi:10.1210/jcem-46-2-277

Cited by 45 publications

(16 citation statements)

References 18 publications

(22 reference statements)

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“…7) (Pang and Rowland, 1977a,b). CL h was calculated for hydrocortisone, correcting for the plasma protein binding (f u b ) from the literature (Robin et al, 1978) and using eq. 7, where Q is the hepatic blood flow rate and f u inc is the unbound fraction in hepatocytes from the bioreactor.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

confidence: 99%

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

et al. 2015

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“…Robin et al [28] using the method of ultrafiltration by means of centrifugation found that the mean percentage value of free cortisol in adults was about 9.7%. Higher free cortisol value (15.9%) in adults was found by Forest et al [14.…”

Section: Discussionmentioning

confidence: 99%

“…Bondy [3] estimated the absolute value of free cortisol at 1 pg/dl and Robin et al [28] at 1.5 pg/dl. According to these authors the level of the hormonal fraction studied de pends neither on sex nor age (within the span of 20 to over 50 years).…”

Section: Discussionmentioning

confidence: 99%

“…fraction of cortisol is considered to be bio logically active [6], although the protein complexes could also show some biological activity [19,28,34], As demonstrated in our previous studies, the total cortisol level in full-term newborns decreases rapidly in the first hours and days of extra-uterine life, reaching the lowest value at 3-5 days after birth, and then it begins to increase [29,30].…”

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confidence: 99%

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Free Cortisol of Human Plasma in the First Three Months of Life

et al. 1990

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Total cortisol as well as percentage and absolute free cortisol values were determined in 75 full-term, 88 premature and 38 small-for-age (born at term) infants in the first 3 months of life. Equilibrium dialysis and radioimmunoassay were used to estimate the percentage value of the unbound fraction and the value of total cortisol from which absolute free cortisol level was calculated, respectively. A systematic decrease in the free cortisol value was observed in all the three groups of infants during the study period (in full-term infants from 32.3 to 19%, in prematures from 36.6 to 20.8%, and in small-for-age infants from 32.3 to 19.2%). A comparison between the percentage values of free cortisol in the groups studied revealed only slight differences which were not significant. The absolute free cortisol values in full-term infants were highest immediately after birth (4.05 μg/dl), then they fell to the lowest level of 0.67 μg/dl observed between the third and fifth days of life, and increased afterwards reaching the level of 1.89 μg/dl in the third month. The absolute free cortisol values in premature newborns at 3–5 days of life exceeded the values observed in full-term subjects. The pattern of free cortisol in the prematures seems to be ‘delayed’ as compared with that in full-term newborns. The absolute free cortisol values in small-for-age infants were much more similar to those found in the full-term subjects, than to those in premature babies.

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“…Complicating factors in the evaluation of serum cortisol levels during acute stress are that the albumin and CBG may decrease. Therefore, the total serum cortisol may be decreased even if the level of free (active) cortisol is unchanged [11] Methods have been developed for measuring serum free cortisol; however, they are technically demanding, expensive, and are not readily available [12]. A ratio of cortisol:CBG has been proposed to determine a free cortisol index that is proportionate to the serum free cortisol [13].…”

Section: Adrenal Insufficiencymentioning

confidence: 99%

Steroid hormones: relevance and measurement in the clinical laboratory

Holst

Soldin

Guo

et al. 2004

Clinics in Laboratory Medicine

134

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The steroid hormones are synthesized in the adrenal cortex, the gonads, and the placenta; are all derived from cholesterol and many are of clinical importance. Steroid hormones are synthesized in the mitochondria and smooth endoplasmic reticulum. Because they are lipophilic, they cannot be stored in vesicles from which they would diffuse easily and are therefore synthesized when needed as precursors. Upon stimulation of the parent cell, steroid hormone precursors are converted to active hormones and diffuse out of the parent cell by simple diffusion as their intracellular concentration rises.Because all steroid hormones are derived from cholesterol, they are not soluble in plasma and other body fluids. As a result, steroids are bound to transport proteins that increase their half-life and insure ubiquitous distribution. The protein-bound steroids are in equilibrium with a small fraction of free steroids, which are 'active.' Steroids can act quickly, by binding to cell surface receptors, or slowly, by binding to cytoplasmic or nucleic receptors and ultimately activate gene transcription.The adrenal glands are composed of the adrenal medulla and the adrenal cortex. The adrenal cortex is divided into three major anatomic zones: the zona glomerulosa, which produces aldosterone; and the zonae fasciculata and reticularis, which together produce cortisol and adrenal androgens. The medulla synthesizes catecholamines. More than 30 steroids are produced in the adrenal cortex; they can be divided into three functional categories: mineralocorticoids, glucocorticoids, and androgens.The steroids that are made almost exclusively in the adrenal glands are cortisol, 11-deoxycortisol, aldosterone, corticosterone, and 11-deoxycorti-costerone. Most other steroid hormones, including the estrogens, are made by the adrenal glands and the gonads [ MineralocorticoidsThe mineralocorticoids are formed in the zona glomerulosa. The main function of the mineralocorticoids is to promote tubular reabsorption of sodium and secretion of potassium and hydrogen ions at the collecting tubule, distal tubule, and collecting ducts [2]. When sodium is reabsorbed, water is absorbed simultaneously. The absorption of sodium and water increases fluid volume and arterial pressure.Aldosterone is the most potent mineralocorticoid and accounts for about 90% of the total mineralocorticoid activity. Mineralocorticoid potency in descending order is: aldosterone, 11-deoxycorticosterone, 18-oxocortisol, corticosterone, and cortisol [1]. Although cortisol has mainly glucocorticoid activity, it also has some mineralocorticoid activity. Cortisol has 1/400 of the potency of aldosterone, but its concentration is about 80 times greater than that of aldosterone [4]. The adrenal production of cortisol is approximately 25 mg/day and that of aldosterone is 100μg/day. Corticosterone has mainly glucocorticoid activity and some mineralocorticoid activity.Aldosterone secretion is regulated primarily by the renin-angiotensin system; it also is stimulated by increased serum potas...

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Assay of Unbound Cortisol in Plasma*

Cited by 45 publications

References 18 publications

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

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

Free Cortisol of Human Plasma in the First Three Months of Life

Steroid hormones: relevance and measurement in the clinical laboratory

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