Measuring cortisol in serum, urine and saliva – are our assays good enough?

El-Farhan, Nadia; Rees, Dafydd Aled; Evans, Carol

doi:10.1177/0004563216687335

Cited by 252 publications

(158 citation statements)

References 133 publications

(220 reference statements)

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“…Recent work has also shown how differences in dexamethasone metabolism, rather than MDD symptoms, can better explain variance in cortisol levels (109), though studies have attempted to control for this by directly sampling serum dexamethasone (14). To counter difficulties with salivary cortisol, it is possible to measure free and bound fractions of serum cortisol directly via liquid chromatography-tandem mass spectrometry; however, reference ranges using this technique for suppression tests are yet to be established (110). Furthermore, the DST only probes GR, whereas the less frequently used, but more physiologically relevant, prednisolone suppression test examines both GR and MR function (111), both of which interact abnormally in MDD pathophysiology.…”

Section: Confounders To Interpreting Cortisol In Mddmentioning

confidence: 99%

Cortisol and Major Depressive Disorder—Translating Findings From Humans to Animal Models and Back

Nandam¹,

Brazel²,

Zhou³

et al. 2020

Front. Psychiatry

174

103

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Major depressive disorder (MDD) is a global problem for which current pharmacotherapies are not completely effective. Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has long been associated with MDD; however, the value of assessing cortisol as a biological benchmark of the pathophysiology or treatment of MDD is still debated. In this review, we critically evaluate the relationship between HPA axis dysfunction and cortisol level in relation to MDD subtype, stress, gender and treatment regime, as well as in rodent models. We find that an elevated cortisol response to stress is associated with acute and severe, but not mild or atypical, forms of MDD. Furthermore, the increased incidence of MDD in females is associated with greater cortisol response variability rather than higher baseline levels of cortisol. Despite almost all current MDD treatments influencing cortisol levels, we could find no convincing relationship between cortisol level and therapeutic response in either a clinical or preclinical setting. Thus, we argue that the absolute level of cortisol is unreliable for predicting the efficacy of antidepressant treatment. We propose that future preclinical models should reliably produce exaggerated HPA axis responses to acute or chronic stress a priori, which may, or may not, alter baseline cortisol levels, while also modelling the core symptoms of MDD that can be targeted for reversal. Combining genetic and environmental risk factors in such a model, together with the interrogation of the resultant molecular, cellular, and behavioral changes, promises a new mechanistic understanding of MDD and focused therapeutic strategies.

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Section: Confounders To Interpreting Cortisol In Mddmentioning

confidence: 99%

Cortisol and Major Depressive Disorder—Translating Findings From Humans to Animal Models and Back

Nandam¹,

Brazel²,

Zhou³

et al. 2020

Front. Psychiatry

174

103

View full text Add to dashboard Cite

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“…However, such techniques present biases related to the low specificity of the analysis antibodies and their considerable affinity for other steroidal hormones. 42 Thus, the salivary cortisol measurement method has become more popular due to the diffusion of cortisol to saliva independently of the salivary flow, the ease of sample collection, and the better differentiation of analysis antibody bindings to steroid hormones. 43,44 Only one study evaluated serum cortisol 25 in this study all included patients are systemically healthy.…”

mentioning

confidence: 99%

Association between Psychological Stress and Periodontitis: A Systematic Review

et al. 2020

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This systematic review aims to investigate the association between psychological stress and periodontitis through analysis of cortisol levels and periodontal clinical parameters. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide and based on PECO (Participants, Exposure, Comparators, Outcomes) question and registered at PROSPERO under the code CRD42017076670. As eligibility criteria, observational studies performed in adult humans presenting periodontitis (P), which evaluated patients exposed (E) and nonexposed to psychological stress (C) and to verify the association between this type of stress and periodontitis (O) were included. The searches were performed until March 2018. The following databases were used: PubMed, Scopus, Web of Science, The Cochrane Library, LILACS, OpenGrey, and Google Scholar. After searches, the duplicate results were removed. The remaining citations were selected according to eligibility criteria in two phases. In the first phase, the title/abstract was evaluated. In the second phase, the articles were chosen previously were assessed by full text. After selection, the studies were submitted to data extraction and risk of bias evaluation by Fowkes and Fulton. A total of 1,386 citations were retrieved. After duplicates removal and selection process, three articles were selected by full text. Among them, two articles reported a positive association between psychological stress and periodontitis. All articles were classified as low risk of bias. Even though two articles highlighted an association between psychological stress and the presence of a possible modulatory pattern of cortisol levels in clinical parameters of periodontitis, more studies are necessary to elucidate this question.

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“…Pretorius et al [4] attributes this not only to differences in the cohorts used to determine the ranges, but also to differences in the techniques used [4]. The assays for determining cortisol concentrations vary greatly [6]. Our findings in the liter-ature reported in table S.3, S.5, S.6 of the Supplementary materials suggest that the same might hold for progesterone.…”

Section: Steroid and Transport Protein Concentrationsmentioning

confidence: 76%

“…By equilibrium dialysis, gel filtration or ultrafiltration direct measurement of free cortisol in human plasma can be done. However, the methods are both time-consuming and labour-intensive [6]. Thus, in most clinical procedures for measuring cortisol levels only the total cortisol concentration is measured [4].…”

Section: Introductionmentioning

confidence: 99%

Analysis and validation of a new extended method for estimating plasma free cortisol including neutrophil elastase and competition from other steroids

Gudmand-Hoeyer

Ottesen

2018

The Journal of Steroid Biochemistry and Molecular Biology

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A non-linear mechanistic model for the distribution of cortisol in plasma on free and bound forms is proposed. The influence of progesterone, testosterone and neutrophil elastase on the cortisol distribution in the blood is investigated. The activity of neutrophil elastase is directly included in the model with the concentration of elastase and the kinetic constants describing the activity of elastase collected in one single input variable. The model is very sensitive towards this input variable and fits data excellently, when it is allowed to be subject specific. The analysis shows that steroids such as testosterone with low affinity for corticosteroid-binding globulin (CBG) do not significantly influence the concentration of free cortisol. Progesterone has a high affinity for CBG, but low plasma concentrations compared to cortisol. Contrary to expectations, progesterone is shown to impact the distribution of cortisol in plasma both under circumstances with high levels as seen in pregnancy and during the normal menstrual cycle of women. Comparing the predictions of our model with predictions made with the equilibrium models by Coolens et al. [1], Dorin et al. [2] and Nguyen et al. [3] shows that the models differ considerably not only in their predictions for free cortisol, but also for cortisol on bound forms; i.e. bound to albumin, intact CBG and elastase-cleaved CBG. Disregarding some of the smallest terms of the model equations a reduced version of the model in form of a fourth order polynomial equation is obtained. The reduced version of the model performs almost identically to the full version and serves as a new formula for calculating the plasma free cortisol concentration.

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Measuring cortisol in serum, urine and saliva – are our assays good enough?

Cited by 252 publications

References 133 publications

Cortisol and Major Depressive Disorder—Translating Findings From Humans to Animal Models and Back

Cortisol and Major Depressive Disorder—Translating Findings From Humans to Animal Models and Back

Association between Psychological Stress and Periodontitis: A Systematic Review

Analysis and validation of a new extended method for estimating plasma free cortisol including neutrophil elastase and competition from other steroids

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