Free cortisol index as a surrogate marker for serum free cortisol

Roux, Carel W. le; Sivakumaran, Sivajenani; Alaghband‐Zadeh, Jamshid; Dhillo, Waljit S.; Kong, Wing May; Wheeler, Michael J.

doi:10.1258/000456302760042182

Cited by 83 publications

(71 citation statements)

References 8 publications

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“…Total plasma cortisol is made up of both bound and free fractions, and free cortisol is the form that is active, because it crosses cell membranes and interacts with receptors. Therefore, measuring both plasma CBG levels and total plasma cortisol levels allows free plasma cortisol to be estimated, which is a better measure of cortisol activity than the measurement of total plasma cortisol alone (29). Our results indicated that both total cortisol and free cortisol levels were higher in the plasma of the patient group than in the plasma of the control group.…”

Section: Discussionmentioning

confidence: 65%

Insulin Resistance Is Associated With Hypercortisolemia in Polynesian Patients Treated With Antipsychotic Medication

Poa¹,

Edgar²

2007

Diabetes Care

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OBJECTIVE -Type 2 diabetes is more prevalent in the indigenous Polynesian population of New Zealand (Maori) than in Europeans. The aim of this study was to determine whether insulin resistance in Maori psychiatric patients was associated with antipsychotic treatment and to investigate the mechanism of an association.RESEARCH DESIGN AND METHODS -Thirty adult Maori psychiatric patients receiving antipsychotic medication for Ͼ6 months and 30 healthy, age-, sex-, and BMI-matched control subjects were enrolled. Early morning fasting blood samples were analyzed for plasma levels of glucose, insulin, A1C, triglycerides, total cholesterol, IGF-1, cortisol, cortisol-binding globulin (CBG), and adiponectin.RESULTS -The patient group had significantly higher median fasting insulin plasma levels than the control group (P ϭ 0.002), which were independent of BMI, age, and sex. In addition, the patient group had significantly higher total cortisol (P ϭ 0.03) and lower CBG levels (P ϭ 0.004) than the control group, resulting in significantly higher levels of free cortisol (P ϭ 0.004). The patient group was also significantly more hypoglycemic (P ϭ 0.026) and hypertriglyceridemic (P ϭ 0.028) than the control group. There was no significant difference in BMI, waist circumference, A1C, total cholesterol, IGF-1, or adiponectin levels between the two groups.CONCLUSIONS -An increase in insulin resistance is seen in Maori psychiatric patients treated with antipsychotic medication. Therefore, Polynesian ethnicity should be considered in prescribing practice and general care of this group. In addition, the hypothalamic-pituitaryadrenal axis may have an important role in the mechanism by which this insulin resistance develops.

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Section: Discussionmentioning

confidence: 65%

Insulin Resistance Is Associated With Hypercortisolemia in Polynesian Patients Treated With Antipsychotic Medication

Poa¹,

Edgar²

2007

Diabetes Care

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“…Foregoing studies can be criticized because of changes in binding proteins such as cortisol-binding globulin (CBG) and albumin, confounding estimation of biologically active free cortisol from total cortisol measurements and thereby assessment of adrenal function [1,4,5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Indeed, low binding proteins may overestimate relative adrenal insufficiency assessed from (increases in) total cortisol.…”

Section: Introductionmentioning

confidence: 99%

Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness

et al. 2011

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Purpose: To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illnessrelated corticosteroid insufficiency. Methods: A prospective study in a mixed intensive care unit from 2004 to 2007. We consecutively included 49 septic and 63 non-septic patients with treatment-insensitive hypotension in whom an adrenocorticotropic hormone (ACTH) test (250 lg) was performed. Serum total and free cortisol (equilibrium dialysis), corticosteroid-binding globulin (CBG) and albumin were assessed. Results: Although a low CBG resulted in a high free cortisol level relative to total cortisol, free and total cortisol and their increases were well correlated (r = 0.77-0.79, P \ 0.001). In sepsis, hypoalbuminemia did not affect total and free cortisol, and increases in total cortisol upon ACTH predicted increases in free cortisol regardless of low binding proteins. In non-sepsis, total cortisol was lower with than without hypoalbuminemia; free cortisol did not differ, since hypoalbuminemia concurred with a low CBG. Increases in total cortisol depended less on binding proteins than on raw levels. The areas under the receiver operating characteristic curve for predicting increases in free from total cortisol were 0.93-0.97 in sepsis and 0.79-0.85 in non-sepsis (P = 0.044 or lower for sepsis vs. non-sepsis). Conclusions: Although the biologically active free cortisol fraction depends on binding proteins, total cortisol correlates to free cortisol in treatment-insensitive hypotension during critical illness. In sepsis, albumin is not an important binding molecule. Subnormal increments in total cortisol upon ACTH suffice in assessing relative adrenal insufficiency, particularly in sepsis.

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“…Several studies suggest that abnormalities in cortisol action and HPA axis control may be a factor that links disturbances of carbohydrate metabolism (which characterize insulin resistance) and obesity (5)(6). In obesity, estimation of plasma cortisol does not reflect the function of the HPA axis (7), and levels of cortisol in obese patients have been reported to be normal (8), low (9), or increased (10). On the contrary, response to different stimuli (high secretion of cortisol after laboratory stress tests or after different exogenous neuropeptides) has been found to be altered (11).…”

mentioning

confidence: 99%

“…Nevertheless, it has been widely used to evaluate the HPA axis in obesity, and the outcomes are contradictory (12)(13)(14). The free cortisol index (FCI)-the total cortisol-to-cortisolbinding globulin ratio (CBG) -has also been proposed to be able to evaluate HPA axis activity (7,15) since it reflects the biologically active fraction of total cortisol (7). Moreover, FCI is significantly associated with several features of insulin resistance syndrome (15).…”

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confidence: 99%

Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients

et al. 2007

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OBJECTIVE -Obesity, insulin resistance, and weight loss have been associated with changes in hypothalamic-pituitary-adrenal (HPA) axis. So far, no conclusive data relating to this association are available. In this study, we aim to investigate the effects of massive weight loss on cortisol suppressibility, cortisol-binding globulin (CBG), and free cortisol index (FCI) in formerly obese women.RESEARCH DESIGN AND METHODS -Ten glucose-normotolerant, fertile, obese women (BMI Ͼ40 kg/m 2 , aged 38.66 Ϯ 13.35 years) were studied before and 2 years after biliopancreatic diversion (BPD) when stable weight was achieved and were compared with age-matched healthy volunteers. Cortisol suppression was evaluated by a 4-mg intravenous dexamethasone suppression test (DEX-ST). FCI was calculated as the cortisol-to-CBG ratio. Insulin sensitivity was measured by an euglycemic-hyperinsulinemic clamp, and insulin secretion was measured by a C-peptide deconvolution method. RESULTS-No difference was found in cortisol suppression after DEX-ST before or after weight loss. A decrease in ACTH was significantly greater in control subjects than in obese (P ϭ 0.05) and postobese women (P Յ 0.01) as was the decrease in dehydroepiandrosterone (P Յ 0.05 and P Յ 0.01, respectively). CBG decreased from 51.50 Ϯ 12.76 to 34.33 Ϯ 7.24 mg/l (P Յ 0.01) following BPD. FCI increased from 11.15 Ϯ 2.85 to 18.16 Ϯ 6.82 (P Յ 0.05). Insulin secretion decreased (52.04 Ϯ 16.71 vs. 30.62 Ϯ 16.32 nmol/m Ϫ2 ; P Յ 0.05), and insulin sensitivity increased by 163% (P Յ 0.0001). Serum CBG was related to BMI (r 0 ϭ 0.708; P ϭ 0.0001), body weight (r 0 ϭ 0.643; P ϭ 0.0001), body fat percent (r 0 ϭ 0.462; P ϭ 0.001), C-reactive protein (r 0 ϭ 0.619; P ϭ 0.004), and leptin (r 0 ϭ 0.579; P ϭ 0.007) and negatively to M value (r 0 ϭ Ϫ0.603; P ϭ 0.005).CONCLUSIONS -After massive weight loss in morbidly obese subjects, an increase of free cortisol was associated with a simultaneous decrease in CBG levels, which might be an adaptive phenomenon relating to environmental changes. This topic, not addressed before, adds new insight into the complex mechanisms linking HPA activity to obesity. Diabetes Care 30:1494-1500, 2007N utritional status and activity of the hypothalamic-pituitary-adrenal (HPA) axis are strictly associated (1,2). However, little is known about the effect of starvation and intentional calorie deprivation on the HPA axis (3,4). The HPA axis controls the secretion of cortisol with excessive secretion being inhibited by negative feedback. Several studies suggest that abnormalities in cortisol action and HPA axis control may be a factor that links disturbances of carbohydrate metabolism (which characterize insulin resistance) and obesity (5-6). In obesity, estimation of plasma cortisol does not reflect the function of the HPA axis (7), and levels of cortisol in obese patients have been reported to be normal (8), low (9), or increased (10). On the contrary, response to different stimuli (high secretion of cortisol after laboratory stress tests or after different exo...

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Free cortisol index as a surrogate marker for serum free cortisol

Abstract: Free cortisol index is a reliable and user-friendly measure of serum free cortisol.

Cited by 83 publications

References 8 publications

Insulin Resistance Is Associated With Hypercortisolemia in Polynesian Patients Treated With Antipsychotic Medication

Insulin Resistance Is Associated With Hypercortisolemia in Polynesian Patients Treated With Antipsychotic Medication

Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness

Massive Weight Loss Decreases Corticosteroid-Binding Globulin Levels and Increases Free Cortisol in Healthy Obese Patients

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