Clinical and Technical Aspects in Free Cortisol Measurement

Choi, Man Ho

doi:10.3803/enm.2022.1549

Cited by 22 publications

(18 citation statements)

References 79 publications

(123 reference statements)

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“…The strengths of this exploratory study are that steroid profiling was performed using tandem mass spectrometry, which has a high analytical sensitivity and selectivity, and thus, the results are far less prone to be impaired by analytical problems of immunoassays [ 17 , 29 ]. This does not preclude measuring the stimulated cortisol-to-corticosterone ratio with immunoassays in future.…”

Section: Discussionmentioning

confidence: 99%

“…The ratio of two key steroids may be less affected by analytical problems in sepsis as both steroids have similar volume of distribution [ 3 ]. In addition, immunoassays of cortisol and corticosterone show low cross-reactivities [ 29 ]. In this way, the RCC combined with corticotropin testing may offer an innovative approach to revisit diagnostic challenges in adrenocortical function during sepsis [ 3 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

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Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Briegel

Möhnle²,

Keh³

et al. 2022

Crit Care

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Rationale Steroid profiles in combination with a corticotropin stimulation test provide information about steroidogenesis and its functional reserves in critically ill patients. Objectives We investigated whether steroid profiles before and after corticotropin stimulation can predict the risk of in-hospital death in sepsis. Methods An exploratory data analysis of a double blind, randomized trial in sepsis (HYPRESS [HYdrocortisone for PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment. Corticotropin tests were performed in patients prior to randomization and in healthy subjects. Cortisol and precursors of glucocorticoids (17-OH-progesterone, 11-desoxycortisol) and mineralocorticoids (11-desoxycorticosterone, corticosterone) were analyzed using the multi-analyte stable isotope dilution method (LC–MS/MS). Measurement results from healthy subjects were used to determine reference ranges, and those from placebo patients to predict in-hospital mortality. Measurements and main results Corticotropin tests from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. In placebo patients (n = 90), a corticotropin-stimulated cortisol-to-corticosterone ratio > 32.2 predicted in-hospital mortality (AUC 0.8 CI 0.70–0.88; sensitivity 83%; and specificity 78%). This ratio also predicted risk of shock development and 90-day mortality. Conclusions In this exploratory analysis, we found that in sepsis mineralocorticoid steroidogenesis was more frequently impaired than glucocorticoid steroidogenesis. The corticotropin-stimulated cortisol-to-corticosterone ratio predicts the risk of in-hospital death. Trial registration Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008, https://clinicaltrials.gov/ct2/show/NCT00670254.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Briegel

Möhnle²,

Keh³

et al. 2022

Crit Care

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show abstract

“…The strengths of this exploratory study are that steroid pro ling was performed using tandem mass spectrometry, which has a high analytical sensitivity and selectivity and thus the results are far less prone to be impaired by analytical problems of immunoassays (20,31). This does not preclude measuring the stimulated cortisol-to-corticosterone ratio with immunoassays in future.…”

Section: Discussionmentioning

confidence: 99%

“…(7,15). In addition, immunoassays of cortisol and corticosterone show low crossreactivities (31). In this way, the RCC combined with corticotropin testing may offer an innovative approach to revisit diagnostic challenges in adrenocortical function during sepsis (20).…”

Section: Discussionmentioning

confidence: 99%

Corticotropin stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Briegel

Möhnle

Keh

et al. 2022

Preprint

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Rationale: Steroid profiles combined with the corticotropin stimulation test can be used to obtain a more complete picture of adrenocortical function in critically ill patients. Objectives: Our objective was to investigate whether steroid profiles before and after corticotropin stimulation predict shock development and mortality in human sepsis. Methods: An exploratory data analysis of a double-blind, randomized trial in sepsis (HYPRESS [Hydrocortisone for the PRevention of Septic Shock]) was performed. The trial included adult patients with sepsis who were not in shock and were randomly assigned to placebo or hydrocortisone treatment (200 mg for 5 days). Corticotropin tests were performed in 206 patients before randomization and in 20 healthy subjects. Samples were analyzed using the multi-analyte stable isotope dilution method (LC-MS/MS) for steroid profiling. Steroid profiles of healthy subjects undergoing corticotropin tests served as controls to determine reference ranges. Measurements and Main Results: Corticotropin test samples from 180 patients and 20 volunteers were included. Compared to healthy subjects, patients with sepsis had elevated levels of 11-desoxycorticosterone and 11-desoxycortisol, consistent with activation of both glucocorticoid and mineralocorticoid pathways before stimulation. After stimulation with corticotropin, the cortisol response was subnormal in 12% and the corticosterone response in 50% of sepsis patients. A predominance of glucocorticoids over mineralocorticoids after corticotropin stimulation (cortisol-corticosterone ratio > 32.2) predicted the development of shock within 14 days and death within 90 days in the placebo group. Conclusions: In this exploratory data analysis, corticotropin stimulated cortisol-to-corticosterone ratio served as a criterion to predict shock development and mortality in sepsis. Clinical trial registered with www.clinicaltrials.gov Identifier: NCT00670254. Registered 1 May 2008.

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“…For something like cortisol, which often is only in concentrations of micrograms per deciliter in the blood or salivary secretions, the minute differences are one such thing that may be overlooked [11]. Cortisol serves a vital function in stress response, playing a role in adapting to change in everything from vitals to overall wellness [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Osteopathic Manipulation as a Method of Cortisol Modification: A Systematic Review

Thibaut¹,

Santarlas²,

Hoppes³

et al. 2023

Cureus

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The effectiveness of osteopathic manipulative treatment (OMT) in the modification of various hormones has been studied; however, there is still a need for quantitative measurements to determine how large of an influence exists. The goal of this meta-analysis is to investigate the implications OMT has on cortisol levels. A systematic literature search restricted to English was performed from October 2022 to November 2022 using Google Scholar, OSTMED.DR, and PubMed and included articles from 2000 onward. Articles were excluded if they did not include a measurement for the control group in their study. We identified 4120 studies for potential inclusion. Of these, a total of four studies met the inclusion criteria, with a total of 135 participants (N= 68 OMT, N= 67 control). Out of the 135 participants, 126 participants (N= 62 OMT, N= 64 control) made up the salivary cortisol studies, and the remaining nine participants made up the serum cortisol studies (OMT N= 6, control N= 3). The National Institutes of Health (NIH) bias assessment tool was utilized to measure the risk of bias. Standard mean differences were calculated for effect size. A mean difference in cortisol of 0.10μg/dl (-10μg/dl, 95%CI -0.15, -0.04) was found when comparing all pre-versus post-cortisol levels with OMT versus sham control groups. OMT demonstrated a 0.10μg/dl larger decrease in cortisol than sham control treatments. The standard mean difference was found to be -0.46 (95%CI -1.40, 0.48) making this finding a medium effect size without significance. Heterogeneity for the salivary analysis measured by I 2 was 0% indicating no significant heterogeneity across studies. When serum cortisol was included, heterogeneity stayed at 0%. A larger number of high-quality studies, especially those specific to serum cortisol, are recommended, to elucidate the relationship between OMT and cortisol. This research suggests OMT reduces cortisol more than sham treatment before versus after OMT treatment, and though the change is small when comparing after one treatment, it may have clinical usage if multiple OMT sessions are performed.

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Clinical and Technical Aspects in Free Cortisol Measurement

Cited by 22 publications

References 79 publications

Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Corticotropin-stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Corticotropin stimulated steroid profiles to predict shock development and mortality in sepsis: From the HYPRESS study

Osteopathic Manipulation as a Method of Cortisol Modification: A Systematic Review

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