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Lotsios N, Vrettou C, Poupouzas G, Chalioti A, Keskinidou C, Pratikaki M, Giannopoulou V, Kotanidou A, Vassiliadi D, Dimopoulou I, Vassiliou A. Glucocorticoid receptor response and glucocorticoid-induced leucine zipper expression in neutrophils of critically ill patients with traumatic and non-traumatic brain injury. Front Endocrinol (Lausanne) 2024; 15:1414785. [PMID: 39314520 PMCID: PMC11416954 DOI: 10.3389/fendo.2024.1414785] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 08/23/2024] [Indexed: 09/25/2024] Open
Abstract
Objective Critically ill patients, including those with brain injuries (BI), are frequently hospitalized in an intensive care unit (ICU). As with other critical states, an adequate stress response is essential for survival. Research on the hypothalamic-pituitary-adrenal gland (HPA) axis function in BI has primarily focused on assessing ACTH and cortisol levels. However, the immunological, metabolic, and hemodynamic effects of glucocorticoids (GCs) are mediated through the glucocorticoid receptor (GCR), a ubiquitously distributed intracellular receptor protein. Data on GCR-α expression and its signaling in acute BI injury are lacking. Methods We designed a prospective observational study, carried out in one academic multi-disciplinary ICU. Forty-two critically ill patients with acute (BI)were included. These patients suffered from traumatic BI (N= 20), subarachnoid hemorrhage (N= 12), intracranial hemorrhage (N= 7), or ischemic stroke (N= 3). All patients were steroid-free. Twenty-four age and sex-matched healthy controls were used for comparison. Results Expression of GCR-α and the glucocorticoid-inducible leucine zipper (GILZ), serum cortisol, interleukins (IL) 6, 8, 10 and TNF- α, and the BI biomarkers glial fibrillary acidic protein (GFAP) and total Tau were measured on ICU admission (within 48 hours) and 5-7 days from admission. Compared to healthy controls, in the critically ill patients with BI, GCR-α mRNA expression was significantly downregulated on admission, and after 5-7 days in the ICU (2.3-fold, p<0.05 and 2.6-fold, p<0.01, respectively). Even though GCR-α was downregulated, its downstream gene, GILZ, was expressed at the same levels as in normal controls on admission and was significantly upregulated 5-7 days following admission (2-fold, p<0.001). TNF-α levels were undetectable at both time-points. GCR-α expression levels inversely correlated with IL-6. The levels of cortisol and the BI biomarkers did not differ between the 2 time-points. Conclusions We provide novel evidence on the downregulated expression and upregulated signaling of the ligand-binding and functionally active GCR-α isoform in the polymorphonuclear neutrophils (PMNs) of critically ill patients with BI. The increased GILZ expression indicates an increased GC sensitivity in the PMNs of BI critically ill patients.
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Affiliation(s)
- N.S. Lotsios
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - C.S. Vrettou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - G. Poupouzas
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - A. Chalioti
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - C. Keskinidou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - M. Pratikaki
- Biochemical Department, Evangelismos Hospital, Athens, Greece
| | - V. Giannopoulou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - A. Kotanidou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - D.A. Vassiliadi
- Department of Endocrinology, Diabetes and Metabolism, National Expertise Center for Rare Endocrine Diseases, Evangelismos Hospital, Athens, Greece
| | - Ioanna Dimopoulou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
| | - A.G. Vassiliou
- First Department of Critical Care Medicine & Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
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Balasamy S, Atchudan R, Arya S, Gunasekaran BM, Nesakumar N, Sundramoorthy AK. Cortisol: Biosensing and detection strategies. Clin Chim Acta 2024; 562:119888. [PMID: 39059481 DOI: 10.1016/j.cca.2024.119888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Revised: 07/22/2024] [Accepted: 07/23/2024] [Indexed: 07/28/2024]
Abstract
Cortisol, a crucial steroid hormone synthesized by the adrenal glands, has diverse impacts on multiple physiological processes, such as metabolism, immune function, and stress management. Disruption in cortisol levels can result in conditions like Cushing's syndrome and Addison's disease. This review provides an in-depth exploration of cortisol, covering its structure, various forms in the body, detection methodologies, and emerging trends in cancer treatment and detection. Various techniques for cortisol detection, including electrochemical, chromatographic, and immunoassay methods were discussed and highlighted for their merits and applications. Electrochemical immunosensing emerges as a promising approach, which offered high sensitivity and low detection limits. Moreover, the review delves into the intricate relationship between cortisol and cancer, emphasizing cortisol's role in cancer progression and treatment outcomes. Lastly, the utilization of biomarkers, in-silico modeling, and machine learning for electrochemical cortisol detection were explored, which showcased innovative strategies for stress monitoring and healthcare advancement.
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Affiliation(s)
- Sesuraj Balasamy
- Centre for Nano-Biosensors, Department of Prosthodontics and Materials Science, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, Tamil Nadu, India
| | - Raji Atchudan
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea
| | - Sandeep Arya
- Department of Physics, University of Jammu, Jammu, Jammu and Kashmir 180006, India
| | - Balu Mahendran Gunasekaran
- School of Chemical & Biotechnology (SCBT), SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India; Center for Nanotechnology & Advanced Biomaterials (CENTAB), SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - Noel Nesakumar
- School of Chemical & Biotechnology (SCBT), SASTRA Deemed University, Thanjavur 613 401, Tamil Nadu, India; Center for Nanotechnology & Advanced Biomaterials (CENTAB), SASTRA Deemed University, Thanjavur 613401, Tamil Nadu, India
| | - Ashok K Sundramoorthy
- Centre for Nano-Biosensors, Department of Prosthodontics and Materials Science, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, Tamil Nadu, India.
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Karuppaiah G, Lee MH, Bhansali S, Manickam P. Electrochemical sensors for cortisol detection: Principles, designs, fabrication, and characterisation. Biosens Bioelectron 2023; 239:115600. [PMID: 37611448 DOI: 10.1016/j.bios.2023.115600] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 08/09/2023] [Accepted: 08/12/2023] [Indexed: 08/25/2023]
Abstract
Psychological stress is a major factor contributing to health discrepancies among individuals. Sustained exposure to stress triggers signalling pathways in the brain, which leading to the release of stress hormones in the body. Cortisol, a steroid hormone, is a significant biomarker for stress management due to its responsibility in the body's reply to stress. The release of cortisol in bloodstream prepares the body for a "fight or flight" response by increasing heart rate, blood pressure, metabolism, and suppressing the immune system. Detecting cortisol in biological samples is crucial for understanding its role in stress and personalized healthcare. Traditional techniques for cortisol detection have limitations, prompting researchers to explore alternative strategies. Electrochemical sensing has emerged as a reliable method for point-of-care (POC) cortisol detection. This review focuses on the progress made in electrochemical sensors for cortisol detection, covering their design, principle, and electroanalytical methodologies. The analytical performance of these sensors is also analysed and summarized. Despite significant advancements, the development of electrochemical cortisol sensors faces challenges such as biofouling, sample preparation, sensitivity, flexibility, stability, and recognition layer performance. Therefore, the need to develop more sensitive electrodes and materials is emphasized. Finally, we discussed the potential strategies for electrode design and provides examples of sensing approaches. Moreover, the encounters of translating research into real world applications are addressed.
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Affiliation(s)
- Gopi Karuppaiah
- Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi, 630 003, Tamil Nadu, India; School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea
| | - Min-Ho Lee
- School of Integrative Engineering, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea
| | - Shekhar Bhansali
- Department of Electrical and Computer Engineering, Florida International University, Miami, FL, 33174, USA.
| | - Pandiaraj Manickam
- Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi, 630 003, Tamil Nadu, India; Academy of Scientific and Innovative Research, Ghaziabad, 201 002, Uttar Pradesh, India.
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Iqbal T, Elahi A, Wijns W, Shahzad A. Cortisol detection methods for stress monitoring in connected health. HEALTH SCIENCES REVIEW 2023; 6:100079. [DOI: 10.1016/j.hsr.2023.100079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Narinx N, David K, Walravens J, Vermeersch P, Claessens F, Fiers T, Lapauw B, Antonio L, Vanderschueren D. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology. Cell Mol Life Sci 2022; 79:543. [PMID: 36205798 PMCID: PMC11803068 DOI: 10.1007/s00018-022-04562-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 08/12/2022] [Accepted: 09/17/2022] [Indexed: 11/03/2022]
Abstract
According to the free hormone hypothesis, biological activity of a certain hormone is best reflected by free rather than total hormone concentrations. A crucial element in this theory is the presence of binding proteins, which function as gatekeepers for steroid action. For testosterone, tissue exposure is governed by a delicate equilibrium between free and total testosterone which is determined through interaction with the binding proteins sex hormone-binding globulin and albumin. Ageing, genetics and various pathological conditions influence this equilibrium, hereby possibly modulating hormonal exposure to the target tissues. Despite ongoing controversy on the subject, strong evidence from recent in vitro, in vivo and human experiments emphasizes the relevance of free testosterone. Currently, however, clinical possibilities for free hormone diagnostics are limited. Direct immunoassays are inaccurate, while gold standard liquid chromatography with tandem mass spectrometry (LC-MS/MS) coupled equilibrium dialysis is not available for clinical routine. Calculation models for free testosterone, despite intrinsic limitations, provide a suitable alternative, of which the Vermeulen calculator is currently the preferred method. Calculated free testosterone is indeed associated with bone health, frailty and other clinical endpoints. Moreover, the added value of free testosterone in the clinical diagnosis of male hypogonadism is clearly evident. In suspected hypogonadal men in whom borderline low total testosterone and/or altered sex hormone-binding globulin levels are detected, the determination of free testosterone avoids under- and overdiagnosis, facilitating adequate prescription of hormonal replacement therapy. As such, free testosterone should be integrated as a standard biochemical parameter, on top of total testosterone, in the diagnostic workflow of male hypogonadism.
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Affiliation(s)
- N Narinx
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000, Leuven, Belgium
- Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
| | - K David
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000, Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - J Walravens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - P Vermeersch
- Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
| | - F Claessens
- Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - T Fiers
- Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - B Lapauw
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - L Antonio
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000, Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - D Vanderschueren
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000, Leuven, Belgium.
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
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Choi MH. Clinical and Technical Aspects in Free Cortisol Measurement. Endocrinol Metab (Seoul) 2022; 37:599-607. [PMID: 35982612 PMCID: PMC9449105 DOI: 10.3803/enm.2022.1549] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 07/22/2022] [Accepted: 07/28/2022] [Indexed: 11/11/2022] Open
Abstract
Accurate measurement of cortisol is critical in adrenal insufficiency as it reduces the risk associated with misdiagnosis and supports the optimization of stress dose. Comprehensive assays have been developed to determine the levels of bioactive free cortisol and their clinical and analytical efficacies have been extensively discussed because the level of total cortisol is affected by changes in the structure or circulating levels of corticoid-binding globulin and albumin, which are the main reservoirs of cortisol in the human body. Antibody-based immunoassays are routinely used in clinical laboratories; however, the lack of molecular specificity in cortisol assessment limits their applicability to characterize adrenocortical function. Improved specificity and sensitivity can be achieved by mass spectrometry coupled with chromatographic separation methods, which is a cutting-edge technology to measure individual as well as a panel of steroids in a single analytical run. The purpose of this review is to introduce recent advances in free cortisol measurement from the perspectives of clinical specimens and issues associated with prospective analytical technologies.
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Affiliation(s)
- Man Ho Choi
- Center for Advanced Biomolecular Recognition, Korea Institute of Science and Technology, Seoul, Korea
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7
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Rison S, Rajeev R, Bhat VS, Mathews AT, Varghese A, Hegde G. Non-enzymatic electrochemical determination of salivary cortisol using ZnO-graphene nanocomposites. RSC Adv 2021; 11:37877-37885. [PMID: 35498093 PMCID: PMC9043917 DOI: 10.1039/d1ra07366d] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 11/04/2021] [Indexed: 12/13/2022] Open
Abstract
Electrochemically deposited ZnO nanoparticles on a pencil graphite electrode (PGE) coated with graphene generate a noteworthy conductive and selective electrochemical sensing electrode for the estimation of cortisol. Electrochemical techniques such as cyclic voltammetry (CV) analysis and electrochemical impedance spectroscopic (EIS) tests were adopted to analyze and understand the nature of the modified sensor. Surface morphological analysis was done using various spectroscopic and microscopic techniques like X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Structural characterization was conducted by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The effect of scan rate, concentration, and cycle numbers was optimized and reported. Differential pulse voltammetric (DPV) analysis reveals that the linear range for the detection of cortisol is 5 × 10−10M − 115 × 10−10 M with a very low-level limit of detection value (0.15 nM). The demonstrated methodology has been excellently functional for the determination of salivary cortisol non-enzymatically at low-level concentration with enhanced selectivity despite the presence of interfering substances. Electrochemically deposited ZnO nanoparticles on a pencil graphite electrode (PGE) coated with graphene generate a noteworthy conductive and selective electrochemical sensing electrode for the estimation of cortisol.![]()
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Affiliation(s)
- Sherin Rison
- Christ Academy Institute For Advanced Studies Christ Nagar Bangalore 560083 India.,Department of Chemistry, CHRIST (Deemed to be University) Bangalore 560029 India
| | - Rijo Rajeev
- Department of Chemistry, CHRIST (Deemed to be University) Bangalore 560029 India
| | - Vinay S Bhat
- Centre for Nano-materials and Displays, B.M.S College of Engineering Bull Temple Road Bangalore 560019 India
| | - Agnus T Mathews
- Department of Chemistry, CHRIST (Deemed to be University) Bangalore 560029 India
| | - Anitha Varghese
- Department of Chemistry, CHRIST (Deemed to be University) Bangalore 560029 India
| | - Gurumurthy Hegde
- Department of Chemistry, CHRIST (Deemed to be University) Bangalore 560029 India .,Centre for Advanced Research and Development (CARD), CHRIST (Deemed to be University) Bangalore 560029 India
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Yener S, Tuna G, Kant M, Akis M, Kara O, Kalas B, Baris M, Islekel GH. Assessment of Plasma-Free Cortisol Concentrations by LC-MS/MS in Patients with Autonomous Cortisol Secretion. Horm Metab Res 2021; 53:752-758. [PMID: 34740277 DOI: 10.1055/a-1661-4126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Autonomous cortisol secretion (ACS) of an adrenal incidentaloma (AI) is associated with mild cortisol excess that could result in poor metabolic and cardiovascular outcomes. The biological activity of glucocorticoids depends on the unbound, free fraction. We aimed to evaluate plasma free cortisol (FC) concentrations in patients with ACS in this cross-sectional study. One hundred and ten AI patients in 3 groups; non-functioning (NFA, n=33), possible ACS (n=65), ACS (n=12) were enrolled. Following measurements were conducted: Clinical data and total serum cortisol (TC), plasma corticotrophin (ACTH), serum dehydroepiandrosterone sulfate (DHEA-S), cortisol after 1 mg dexamethasone by both immunoassay and LC-MS/MS (DexF), serum corticosteroid binding globulin (CBG), plasma dexamethasone concentration [DEX] and plasma FC by LC-MS/MS. Patients with ACS featured an unfavorable metabolic profile. Plasma [DEX] and serum CBG levels were similar between groups. Plasma FC was significantly higher in ACS when compared to NFA and possible ACS groups p<0.05 and p<0.01, respectively. In multiple regression analysis DexF (beta=0.402, p<0.001) and CBG (beta=-0.257, p=0.03) remained as the independent predictors of plasma FC while age, sex, BMI, smoking habit, and existing cardiovascular disease did not make a significant contribution to the regression model. In conclusion, the magnitude of cortisol excess in ACS could lead to increased plasma FC concentrations. Further studies in AI patients are needed to demonstrate whether any alterations of cortisol affinity for CBG exist and to establish whether plasma FC concentrations predict the unfavorable metabolic profile in ACS.
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Affiliation(s)
- Serkan Yener
- Division of Endocrinology, Dokuz Eylul University, Izmir, Turkey
| | - Gamze Tuna
- Department of Molecular Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Melis Kant
- Department of Medical Biochemistry, Dokuz Eylul University, Izmir, Turkey
- Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, USA
| | - Merve Akis
- Department of Medical Biochemistry, Balıkesir University, Balıkesir, Turkey
| | - Ozlem Kara
- Department of Internal Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Busra Kalas
- Department of Internal Medicine, Dokuz Eylul University, Izmir, Turkey
| | - Mustafa Baris
- Department of Radiology, Dokuz Eylul University, Izmir, Turkey
| | - Gul Huray Islekel
- Department of Molecular Medicine, Dokuz Eylul University, Izmir, Turkey
- Department of Medical Biochemistry, Dokuz Eylul University, Izmir, Turkey
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Turgut D, Piskinpasa SV, Keskin H, Agbaht K, Coskun Yenigun E, Dede F. Occult Adrenal Insufficiency in Renal Amyloidosis Patients. Medeni Med J 2021; 36:52-57. [PMID: 33828890 PMCID: PMC8020191 DOI: 10.5222/mmj.2021.93902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 03/17/2021] [Indexed: 11/29/2022] Open
Abstract
Objective Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. Methods Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 μg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. Results Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients’ stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). Conclusion ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.
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Affiliation(s)
- Didem Turgut
- Baskent University Ankara Hospital, Department of Internal Medicine, Division of Nephrology, Ankara, Turkey
| | | | - Havva Keskin
- Istanbul Medeniyet University Goztepe Training and Research Hospital, Department of Internal Medicine, Istanbul, Turkey
| | - Kemal Agbaht
- Defne Hospital, Division of Endocrinology and Metabolism, Hatay, Turkey
| | - Ezgi Coskun Yenigun
- University of Health Sciences, Ankara Bilkent City Hospital, Division of Nephrology, Ankara, Turkey
| | - Fatih Dede
- University of Health Sciences, Ankara Bilkent City Hospital, Division of Nephrology, Ankara, Turkey
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Tripathi A, Thakur RS, Kalita J, Patel DK, Misra UK. Is cerebral salt wasting related to sympathetic dysregulation in tuberculous meningitis? Neurosci Lett 2021; 747:135671. [PMID: 33516801 DOI: 10.1016/j.neulet.2021.135671] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 01/12/2021] [Accepted: 01/18/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Cerebral Salt wasting (CSW) is common in Tuberculous Meningitis (TBM) and is suggested to be due to sympathetic dysregulation of renal blood supply but has not been proven. OBJECTIVE To evaluate plasma Catecholamines in TBM patients with CSW and correlate with the markers of stress. MATERIALS AND METHODS The diagnosis of TBM was based on clinical, CSF and MRI criteria. Catecholamines level was measured by LC-MS on admission, at the time of hyponatremia and on correction of hyponatremia. Catecholamine levels were correlated with clinical and laboratory markers of stress, hyponatremia and severity of CSW using pre-defined criteria. RESULTS There were 24 patients with TBM (12 with CSW) and 12 controls. The median age of patients was 31 (18-75) years and 12 (50 %) were females. TBM patients with CSW had significantly higher levels of catecholamines compared to controls (p < 0.001). TBM patients with CSW had higher levels of norepinephrine than those without CSW (p = 0.034). Sequential studies revealed that dopamine and epinephrine increased at the time of hyponatremia and declined on its correction. Severity of TBM was related to dopamine (p = 0.04) and severity of CSW was related to epinephrine (p = 0.016). CONCLUSION CSW in TBM seems to be related to catecholamine dysregulation.
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Affiliation(s)
- Abhilasha Tripathi
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India; Department of Respiratory Medicine, King George's Medical University, Lucknow, India
| | - Ravindra Singh Thakur
- Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Jayantee Kalita
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | - Devendra Kumar Patel
- Analytical Chemistry Laboratory, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Usha K Misra
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
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Castle-Kirszbaum M, Kyi M, Wright C, Goldschlager T, Danks RA, Parkin WG. Hyponatraemia and hypernatraemia: Disorders of Water Balance in Neurosurgery. Neurosurg Rev 2021; 44:2433-2458. [PMID: 33389341 DOI: 10.1007/s10143-020-01450-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/26/2020] [Accepted: 11/25/2020] [Indexed: 12/23/2022]
Abstract
Disorders of tonicity, hyponatraemia and hypernatraemia, are common in neurosurgical patients. Tonicity is sensed by the circumventricular organs while the volume state is sensed by the kidney and peripheral baroreceptors; these two signals are integrated in the hypothalamus. Volume is maintained through the renin-angiotensin-aldosterone axis, while tonicity is defended by arginine vasopressin (antidiuretic hormone) and the thirst response. Edelman found that plasma sodium is dependent on the exchangeable sodium, potassium and free-water in the body. Thus, changes in tonicity must be due to disproportionate flux of these species in and out of the body. Sodium concentration may be measured by flame photometry and indirect, or direct, ion-sensitive electrodes. Only the latter method is not affected by changes in plasma composition. Classification of hyponatraemia by the volume state is imprecise. We compare the tonicity of the urine, given by the sodium potassium sum, to that of the plasma to determine the renal response to the dysnatraemia. We may then assess the activity of the renin-angiotensin-aldosterone axis using urinary sodium and fractional excretion of sodium, urate or urea. Together, with clinical context, these help us determine the aetiology of the dysnatraemia. Symptomatic individuals and those with intracranial catastrophes require prompt treatment and vigilant monitoring. Otherwise, in the absence of hypovolaemia, free-water restriction and correction of any reversible causes should be the mainstay of treatment for hyponatraemia. Hypernatraemia should be corrected with free-water, and concurrent disorders of volume should be addressed. Monitoring for overcorrection of hyponatraemia is necessary to avoid osmotic demyelination.
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Affiliation(s)
| | - Mervyn Kyi
- Department of Endocrinology, Melbourne Health, Melbourne, Australia
| | - Christopher Wright
- Department of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia
| | - Tony Goldschlager
- Department of Neurosurgery, Monash Health, Melbourne, Australia.,Department of Surgery, Monash University, Melbourne, Australia
| | - R Andrew Danks
- Department of Neurosurgery, Monash Health, Melbourne, Australia.,Department of Surgery, Monash University, Melbourne, Australia
| | - W Geoffrey Parkin
- Department of Surgery, Monash University, Melbourne, Australia.,Department of Intensive Care, Monash Health, Melbourne, Australia
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12
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Zaman S, Almazrouei R, Sam AH, DiMarco AN, Todd JF, Palazzo FF, Tan T, Dhillo WS, Meeran K, Wernig F. Synacthen Stimulation Test Following Unilateral Adrenalectomy Needs to Be Interpreted With Caution. Front Endocrinol (Lausanne) 2021; 12:654600. [PMID: 34046013 PMCID: PMC8147556 DOI: 10.3389/fendo.2021.654600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 04/28/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center. METHODS Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded. RESULTS The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement. CONCLUSIONS Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.
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Affiliation(s)
- Shamaila Zaman
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- *Correspondence: Shamaila Zaman, ; Florian Wernig,
| | - Raya Almazrouei
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- Endocrine Division, Tawam Hospital, Al Ain, United Arab Emirates
| | - Amir H. Sam
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, United Kingdom
| | - Aimee N. DiMarco
- Department of Endocrine and Thyroid Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Jeannie F. Todd
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Fausto F. Palazzo
- Department of Endocrine and Thyroid Surgery, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Tricia Tan
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, United Kingdom
| | - Waljit S. Dhillo
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, United Kingdom
| | - Karim Meeran
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, United Kingdom
| | - Florian Wernig
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- *Correspondence: Shamaila Zaman, ; Florian Wernig,
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13
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McBride ML, Burdick Sanchez NC, Carroll JA, Broadway PR, Ortiz XA, Collier JL, Chapman JD, McLean DJ, Kattesh HG, Gillespie BE, Xiao Y, Collier RJ. Response to adrenocorticotropic hormone or corticotrophin-releasing hormone and vasopressin in lactating cows fed an immunomodulatory supplement under thermoneutral or acute heat stress conditions. J Dairy Sci 2020; 103:6612-6626. [PMID: 32307158 DOI: 10.3168/jds.2019-17548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 02/10/2020] [Indexed: 11/19/2022]
Abstract
Adrenal responsiveness was tested in nonpregnant, lactating Holstein dairy cows fed diets supplemented with OmniGen-AF (OG; Phibro Animal Health Corp., Teaneck, NJ), an immune modulator, and in nonsupplemented control (CON) cows following bolus infusions of a combination of corticotropin-releasing hormone (CRH; 0.3 µg/kg of BW) and arginine vasopressin (VP; 1.0 µg/kg of BW) or ACTH (0.1 IU/kg of BW) in 2 environments: thermoneutral [TN; temperature-humidity index (THI) <60] for 24 h/d and heat stress (HS; THI >68 for 17 h/d). Cows (506) were initially fed OG (n = 254) or CON (n = 252) diets for 44 d before selection of a subgroup of cows (n = 12; 6 OG, 6 CON) for the study. The 2 subgroups were balanced for parity, milk yield, and days in milk. All cows were transported to and housed in 2 environmentally controlled rooms at the University of Arizona Agricultural Research Complex (Tucson). Cows were given 3 d to acclimate to the rooms and then underwent 12 d of TN conditions and then 8 d of HS conditions for a total of 24 d on experiment. Cows were infused with CRH-VP on d 9 of TN and on d 1 of HS and with ACTH on d 10 of TN and on d 2 of HS. Hormone infusions took place at 1000 h (0 h) on each infusion day. Blood samples, taken in 30-min intervals, were first collected at 0800 h (-2 h) and were drawn until 1800 h (8 h). Before infusion, serum progesterone was elevated in OG cows compared with CON cows. Infusion of releasing factors (CRH-VP or ACTH) caused increases in serum cortisol and progesterone, but cortisol release was greater in CON cows than in OG cows during HS, whereas progesterone did not differ between the 2 treatments. Serum ACTH increased following infusion of releasing factors, but this increase was greater following CRH-VP infusion than ACTH infusion. Serum bovine corticosteroid-binding globulin also increased following infusion of releasing factors in both treatment groups, but this increase was greater during HS in cows fed OG. The free cortisol index (FCI) increased following CRH-VP and ACTH and was higher in HS than in TN for both OG and CON cows. However, the FCI response was blunted in OG cows compared with CON cows during HS. Heat stress enhanced the adrenal response to releasing factors. Additionally, the adrenal cortisol and FCI response to releasing factors was reduced during acute heat stress in cows fed OG. Collectively, these data suggest that OG supplementation reduced the adrenal responsiveness to factors regulating cortisol secretion during acute HS.
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Affiliation(s)
- M L McBride
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson 85719
| | - N C Burdick Sanchez
- USDA Agricultural Research Service Livestock Issues Research Unit, Lubbock, TX 79403
| | - J A Carroll
- USDA Agricultural Research Service Livestock Issues Research Unit, Lubbock, TX 79403
| | - P R Broadway
- USDA Agricultural Research Service Livestock Issues Research Unit, Lubbock, TX 79403
| | - X A Ortiz
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson 85719
| | - J L Collier
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson 85719
| | - J D Chapman
- Phibro Animal Health Corp., Teaneck, NJ 07666
| | - D J McLean
- Phibro Animal Health Corp., Teaneck, NJ 07666
| | - H G Kattesh
- Department of Animal Science, University of Tennessee, Knoxville 37996
| | - B E Gillespie
- Department of Animal Science, University of Tennessee, Knoxville 37996
| | - Y Xiao
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson 85719
| | - R J Collier
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson 85719.
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14
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Vassiliou AG, Stamogiannos G, Jahaj E, Botoula E, Floros G, Vassiliadi DA, Ilias I, Tsagarakis S, Tzanela M, Orfanos SE, Kotanidou A, Dimopoulou I. Longitudinal evaluation of glucocorticoid receptor alpha/beta expression and signalling, adrenocortical function and cytokines in critically ill steroid-free patients. Mol Cell Endocrinol 2020; 501:110656. [PMID: 31756425 DOI: 10.1016/j.mce.2019.110656] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 10/10/2019] [Accepted: 11/16/2019] [Indexed: 01/23/2023]
Abstract
PURPOSE Glucocorticoid actions are mediated by the glucocorticoid receptor (GCR) whose dysfunction leads to glucocorticoid tissue resistance. Our objective was to evaluate GCR-α and GCR-β expression and key steps in the GCR signalling cascade in critical illness. METHODS Expression of GCR and major GCR-target genes, cortisol, adrenocorticotropin (ACTH) and cytokines was measured in 42 patients on ICU admission and on days 4, 8, and 13. Twenty-five age- and sex-matched subjects were used as controls. RESULTS Acutely, mRNA expression of GCR-α was 10-fold and of GCR-β 3-fold the expression of controls, while during the sub-acute phase expression of both isoforms was lower compared to controls. Expression of FKBP5 and GILZ decreased significantly. Cortisol levels remained elevated and ACTH increased during the 13-day period. CONCLUSIONS GCR expression and hypothalamic-pituitary-adrenal axis function undergo a biphasic response during critical illness. The dissociation between low GCR expression and high cortisol implies an abnormal stress response.
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Affiliation(s)
- Alice G Vassiliou
- 1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Georgios Stamogiannos
- 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Edison Jahaj
- 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Efi Botoula
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece
| | - Georgios Floros
- 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Dimitra A Vassiliadi
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece
| | - Ioannis Ilias
- Endocrine Unit, Elena Venizelou Hospital, Athens, Greece
| | - Stylianos Tsagarakis
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece
| | - Marinella Tzanela
- Department of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece
| | - Stylianos E Orfanos
- 1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece; 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Anastasia Kotanidou
- 1st Department of Critical Care Medicine & Pulmonary Services, GP Livanos and M Simou Laboratories, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece; 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece
| | - Ioanna Dimopoulou
- 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Athens Medical School, National & Kapodistrian University of Athens, Athens, Greece.
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15
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McAfee JM, Kattesh HG, Lindemann MD, Voy BH, Kojima CJ, Burdick Sanchez NC, Carroll JA, Gillespie BE, Saxton AM. Effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation to lactating sows on growth and indicators of stress in the postweaned pig1,2. J Anim Sci 2020; 97:4453-4463. [PMID: 31545382 DOI: 10.1093/jas/skz300] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Accepted: 09/18/2019] [Indexed: 12/14/2022] Open
Abstract
Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA) are precursors for lipid metabolites that reduce inflammation. Two experiments were conducted to test the hypothesis that enriching the sow diet in n-3 PUFA during late gestation and throughout lactation reduces stress and inflammation and promotes growth in weaned pigs. A protected fish oil product (PFO; Gromega) was used to enrich the diet in n-3 PUFA. In the initial experiment, time-bred gilts were fed a gestation and lactation diet supplemented with 0% (control; n = 5), 0.25% (n = 4), 0.5% (n = 4), or 1% (n = 5) PFO from 101 ± 2 d of gestation to day 16 of lactation. Adding 1% PFO to the diet increased the n-3:n-6 PUFA ratio in colostrum and milk compared with controls (P = 0.05). A subsequent experiment was performed to determine whether supplementing the sow diet with 1% PFO improved growth and reduced circulating markers of acute inflammation and stress in the offspring. Plasma was harvested from piglets (16 per treatment group) on day 0 (d of weaning) and days 1 and 3 postweaning. Pigs from the 1% PFO treatment group weighed more (P = 0.03) on day 3 postweaning and had a greater (P ˂ 0.05) n-3:n-6 PUFA ratio in plasma on each day sampled compared with 0% PFO controls. There was an overall treatment effect on plasma total cortisol (P = 0.03) and haptoglobin (P = 0.04), with lesser concentrations in pigs on the 1% PFO diet. Plasma corticosteroid-binding globulin (CBG) concentrations were not different between treatment groups but were less (P ˂ 0.001) on days 1 and 3 when compared with day 0. The resultant free cortisol index [FCI (cortisol/CBG)] was less (P = 0.02) on days 1 and 3 for pigs from the 1% treatment group compared with the controls. An ex vivo lipopolysaccharide (LPS) challenge of whole blood collected on days 0 and 1 was used to determine whether 1% PFO attenuated release of inflammatory cytokines (IL-1β, IL-6, and TNF-α). Blood from pigs within the 1% PFO treatment group tended (P = 0.098) to have a lesser mean concentration of TNF-α in response to LPS compared with blood from controls. These results suggest that providing a PFO supplement as 1% of the diet to sows beginning in late gestation and during lactation can increase the n-3:n-6 PUFA ratio in their offspring, which may improve growth and reduce the acute physiological stress response in the pigs postweaning.
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Affiliation(s)
- John M McAfee
- Department of Animal Science, University of Tennessee, Knoxville, TN
| | - Henry G Kattesh
- Department of Animal Science, University of Tennessee, Knoxville, TN
| | - Merlin D Lindemann
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY
| | - Brynn H Voy
- Department of Animal Science, University of Tennessee, Knoxville, TN
| | - Cheryl J Kojima
- Department of Animal Science, University of Tennessee, Knoxville, TN
| | | | | | | | - Arnold M Saxton
- Department of Animal Science, University of Tennessee, Knoxville, TN
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16
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Defolie C, Merkling T, Fichtel C. Patterns and variation in the mammal parasite-glucocorticoid relationship. Biol Rev Camb Philos Soc 2020; 95:74-93. [PMID: 31608587 DOI: 10.1111/brv.12555] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2019] [Revised: 08/23/2019] [Accepted: 09/03/2019] [Indexed: 01/24/2023]
Abstract
Parasites are ubiquitous and can strongly affect their hosts through mechanisms such as behavioural changes, increased energetic costs and/or immunomodulation. When parasites are detrimental to their hosts, they should act as physiological stressors and elicit the release of glucocorticoids. Alternatively, previously elevated glucocorticoid levels could facilitate parasite infection due to neuroimmunomodulation. However, results are equivocal, with studies showing either positive, negative or no relationship between parasite infection and glucocorticoid levels. Since factors such as parasite type, infection severity or host age and sex can influence the parasite-glucocorticoid relationship, we review the main mechanisms driving this relationship. We then perform a phylogenetic meta-analysis of 110 records from 65 studies in mammalian hosts from experimental and observational studies to quantify the general direction of this relationship and to identify ecological and methodological drivers of the observed variability. Our review produced equivocal results concerning the direction of the relationship, but there was stronger support for a positive relationship, although causality remained unclear. Mechanisms such as host manipulation for parasite survival, host response to infection, cumulative effects of multiple stressors, and neuro-immunomodulatory effects of glucocorticoids could explain the positive relationship. Our meta-analysis results revealed an overall positive relationship between glucocorticoids and parasitism among both experimental and observational studies. Because all experimental studies included were parasite manipulations, we conclude that parasites caused in general an increase in glucocorticoid levels. To obtain a better understanding of the directionality of this link, experimental manipulation of glucocorticoid levels is now required to assess the causal effects of high glucocorticoid levels on parasite infection. Neither parasite type, the method used to assess parasite infection nor phylogeny influenced the relationship, and there was no evidence for publication bias. Future studies should attempt to be as comprehensive as possible, including moderators potentially influencing the parasite-glucocorticoid relationship. We particularly emphasise the importance of testing hosts of a broad age range, concomitantly measuring sex hormone levels or at least reproductive status, and for observational studies, also considering food availability, host body condition and social stressors to obtain a better understanding of the parasite-glucocorticoid relationship.
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Affiliation(s)
- Charlotte Defolie
- Sociobiology/Anthropology Department, University of Göttingen, Kellnerweg 6, 37077, Göttingen, Germany.,Behavioral Ecology & Sociobiology Unit, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077, Göttingen, Germany.,Leibniz ScienceCampus "Primate Cognition", German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany
| | - Thomas Merkling
- Department of Natural Resource Sciences, McGill University, Macdonald-Stewart Building, 21111 Lakeshore Road, Ste. Anne de Bellevue, Québec, H9X 3V9, Canada
| | - Claudia Fichtel
- Behavioral Ecology & Sociobiology Unit, German Primate Center, Leibniz Institute for Primate Research, Kellnerweg 4, 37077, Göttingen, Germany.,Leibniz ScienceCampus "Primate Cognition", German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany
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17
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Nandish HK, Arun CS, Nair HR, Gopalakrishna R, Kumar H, Venu RP. Adrenal insufficiency in decompensated cirrhotic patients without infection: prevalence, predictors and impact on mortality. J R Coll Physicians Edinb 2019; 49:277-281. [PMID: 31808452 DOI: 10.4997/jrcpe.2019.405] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Relative adrenal insufficiency (RAI) is common in compensated and decompensated chronic liver disease in the presence of sepsis. This study was performed to find out the prevalence of RAI in decompensated cirrhotic patients presenting with hepatic encephalopathy and variceal bleeding without any evidence of infection. METHODS The study prospectively included 75 cirrhotic patients with signs of decompensation. The short Synacthen test (SST) was performed on all patients after ruling out infection. Patients with positive blood, urine, sputum, ascitic and pleural fluid cultures or evidence of infection on chest X-ray and those with elevated procalcitonin levels (>0.05 ng/ml) were excluded. RAI in critical illness was defined by a delta cortisol level (difference between basal and post-stimulation cortisol) of ≤9 μg/dl after SST. RESULTS The mean age of the study population was 54 ± 11 years. Upper gastrointestinal bleed and hepatic encephalopathy were seen in 56.6% and 41.5%, respectively, and both were seen in 1.9%. Of the 75 patients, 55 (73%) were in Child-Turcotte-Pugh (CTP) class C and the mean model for end-stage liver disease (MELD) score was 21 ± 7. Forty-five patients (60%) met our criteria for RAI. Those with RAI had lower serum albumin (2.4 ± 0.5 g/dl vs 2.7 ± 0.5 g/dl, p = 0.03) and higher MELD scores (22 ± 7 vs 19 ± 6, p = 0.03). Prevalence of RAI in CTP class C was 65% (36 out of 55 patients) compared to 45% (9 out of 20 patients) in Child-Pugh stage A and B. Similarly, 82% (23 out of 28 patients) with MELD scores >25 had RAI compared to 54% with MELD scores <20. None of biochemical parameters were predictive of RAI on logistic regression analysis. Three-month mortality rate was not significantly different in patients with or without adrenal insufficiency (44% vs 28%, p = 0.11). CONCLUSION The present study showed RAI to be common in noninfected decompensated cirrhotic patients, but did not predict 3-month mortality. There were no other predictive factors in those with RAI. Hence, in patients with cirrhosis without infection, the clinical utility of routine adrenal function testing needs further elucidation.
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Affiliation(s)
- Hullenahalli K Nandish
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
| | - Chankramath S Arun
- Department of Endocrinology, Amrita Institute of Medical Sciences, Ponekkara, Kochi-41, India,
| | - Harikumar R Nair
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
| | - Rajesh Gopalakrishna
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
| | - Harish Kumar
- Department of Endocrinology and Metabolism, Amrita Institute of Medical Sciences, Kerala, India
| | - Rama P Venu
- Centre for Liver Diseases, Digestive Diseases Institute, Amrita Institute of Medical Sciences, Kerala, India
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18
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Yan YR, Zhang L, Lin YN, Wei Y, Li N, Sun XW, Zhou JP, Li QY. The Association of Salivary Biomarkers With the Severity of Obstructive Sleep Apnea and Concomitant Hypertension. Am J Med Sci 2019; 357:468-473. [PMID: 31126512 DOI: 10.1016/j.amjms.2019.03.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Revised: 03/17/2019] [Accepted: 03/18/2019] [Indexed: 01/03/2023]
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19
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Ray P, Steckl AJ. Label-Free Optical Detection of Multiple Biomarkers in Sweat, Plasma, Urine, and Saliva. ACS Sens 2019; 4:1346-1357. [PMID: 30900871 DOI: 10.1021/acssensors.9b00301] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
We report a novel label-free quantitative detection of human performance "stress" biomarkers in different body fluids based on optical absorbance of the biomarkers in the ultraviolet (UV) region. Stress biomarker (hormones and neurotransmitters) concentrations in bodily fluids (blood, sweat, urine, saliva) predict the physical and mental state of the individual. The stress biomarkers primarily focused on in this manuscript are cortisol, serotonin, dopamine, norepinephrine, and neuropeptide Y. UV spectroscopy of stress biomarkers performed in the 190-400 nm range has revealed primary and secondary absorption peaks at near-UV wavelengths depending on their molecular structure. UV characterization of individual and multiple biomarkers is reported in various biofluids. A microfluidic/optoelectronic platform for biomarker detection is reported, with a prime focus toward cortisol evaluation. The current limit of detection of cortisol in sweat is ∼200 ng/mL (∼0.5 μM), which is in the normal (healthy) range. Plasma samples containing both serotonin and cortisol resulted in readily detectable absorption peaks at 203 (serotonin) and 247 (cortisol) nm, confirming feasibility of simultaneous detection of multiple biomarkers in biofluid samples. UV spectroscopy performed on various stress biomarkers shows a similar increasing absorption trend with concentration. The detection mechanism is label free, applicable to a variety of biomarker types, and able to detect multiple biomarkers simultaneously in various biofluids. A microfluidic flow cell has been fabricated on a polymer substrate to enable point-of-use/care UV measurement of target biomarkers. The overall sensor combines sample dispensing and fluid transport to the detection location with optical absorption measurements with a UV light emitting diode (LED) and photodiode. The biomarker concentration is indicated as a function of photocurrent generated at the target wavelength.
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Affiliation(s)
- Prajokta Ray
- Nanoelectronics Laboratory, University of Cincinnati, Cincinnati, Ohio 45221-0030, United States of America
| | - Andrew J. Steckl
- Nanoelectronics Laboratory, University of Cincinnati, Cincinnati, Ohio 45221-0030, United States of America
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20
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Singh RR, Walia R, Sachdeva N, Bhalla A, Singh A, Singh V. Relative adrenal insufficiency in cirrhotic patients with ascites (hepatoadrenal syndrome). Dig Liver Dis 2018; 50:1232-1237. [PMID: 29887344 DOI: 10.1016/j.dld.2018.05.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 04/11/2018] [Accepted: 05/12/2018] [Indexed: 02/08/2023]
Abstract
AIM Relative adrenal insufficiency (RAI) has been reported in critically ill patients with cirrhosis. We evaluated the prevalence of RAI and its relationship to clinical course in non-septic cirrhosis patients with ascites. METHODS The study included 66 consecutive non-septic cirrhosis patients with ascites. RAI was defined by a delta cortisol lower than 9 μg/dL and/or a peak cortisol lower than 18 μg/dL. RESULTS Sixty-six patients with cirrhosis and ascites were studied. The mean Child-Turcotte-Pugh (CTP) and model for end stage liver disease (MELD) scores were 10.6 ± 1.9 and 21.5 ± 7.3, respectively. The prevalence of RAI in patients with cirrhosis and ascites was 47% (31/66). The prevalence of RAI in patients with and without spontaneous bacterial peritonitis, renal failure and type 1 hepatorenal syndrome (HRS) was comparable. Baseline hyponatremia was common in RAI (42% versus 17%, p = 0.026). There was a significant correlation of prevalence of RAI with prothrombin time, international normalized ratio, MELD scores and CTP class. During follow-up, there was no association between RAI and the risk to develop new infections, severe sepsis, type 1 HRS and death. CONCLUSIONS RAI is common in non-septic cirrhotic patients with ascites and its prevalence increases with severity of liver disease. However, it does not affect the short-term outcome in these patients.
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Affiliation(s)
- Rajiv Ranjan Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rama Walia
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Naresh Sachdeva
- Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashish Bhalla
- Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Akash Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Virendra Singh
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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21
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Prete A, Yan Q, Al-Tarrah K, Akturk HK, Prokop LJ, Alahdab F, Foster MA, Lord JM, Karavitaki N, Wass JA, Murad MH, Arlt W, Bancos I. The cortisol stress response induced by surgery: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 2018; 89:554-567. [PMID: 30047158 DOI: 10.1111/cen.13820] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 07/12/2018] [Accepted: 07/17/2018] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. DESIGN We performed a systematic review and meta-analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. METHODS We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta-analysis and plotted over time. RESULTS We included 71 studies reporting peri-operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri-operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. CONCLUSIONS The peri-operative cortisol stress response is dynamic and influenced by patient-specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.
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Affiliation(s)
- Alessandro Prete
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
| | - Qi Yan
- Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Khaled Al-Tarrah
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Halis K Akturk
- Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado
| | - Larry J Prokop
- Mayo Clinic Libraries, Mayo Clinic, Rochester, Minnesota
| | - Fares Alahdab
- Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota
| | - Mark A Foster
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
- NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham & Royal Centre for Defence Medicine, Birmingham, UK
| | - Janet M Lord
- Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Niki Karavitaki
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
| | - John A Wass
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK
| | - Mohammad H Murad
- Evidence-based Practice Center, Mayo Clinic, Rochester, Minnesota
| | - Wiebke Arlt
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
| | - Irina Bancos
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
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Kämäräinen S, Mäki M, Tolonen T, Palleschi G, Virtanen V, Micheli L, Sesay AM. Disposable electrochemical immunosensor for cortisol determination in human saliva. Talanta 2018; 188:50-57. [DOI: 10.1016/j.talanta.2018.05.039] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 05/07/2018] [Accepted: 05/09/2018] [Indexed: 02/05/2023]
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Weintrob N, Davidov AS, Becker AS, Israeli G, Oren A, Eyal O. SERUM FREE CORTISOL DURING GLUCAGON STIMULATION TEST IN HEALTHY SHORT-STATURED CHILDREN AND ADOLESCENTS. Endocr Pract 2018; 24:288-293. [PMID: 29547045 DOI: 10.4158/ep-2017-0132] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE The total cortisol (TC) response may be measured during the glucagon stimulation test (GST) for growth hormone (GH) reserve in order to assess the integrity of the hypothalamic-pituitary-adrenal (HPA) axis. Measurements of TC are unreliable in conditions of albumin and cortisol-binding globulin (CBG) alterations (e.g., hypoproteinemia or CBG deficiency). We aimed to measure the serum free cortisol (sFC) response to the GST in children and adolescents and determine whether it could predict the GH response to glucagon stimulation. METHODS Infants and children with either short stature or growth attenuation who were referred for evaluation of GH reserve underwent the GST. RESULTS The study population consisted of 103 subjects (62 females), median age 3.9 years (range, 0.5-14). The mean basal and peak TC levels were 13.3 ± 6.7 μg/dL and 29.6 ± 8.8 μg/dL, respectively. The mean basal and peak sFC levels were 0.7 ± 0.8 μg/dL and 1.7 ± 1.1 μg/dL, respectively. There was a negative correlation between peak TC and age ( r = -0.3, P = .007) but not between peak sFC and age ( r = -0.09, P = .36). Ninety-five percent of the patients had peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL. CONCLUSION Our results on a cohort of healthy short-statured children can serve as reference values for the sFC response during GST. Based on these results, we propose peak TC levels >15.8 μg/dL and peak sFC levels >0.6 μg/dL for defining normalcy of the HPA axis during the GST in children and adolescents. ABBREVIATIONS ACTH = adrenocorticotrophic hormone BMI = body mass index CBG = cortisol-binding globulin GH = growth hormone GST = glucagon stimulation test HPA = hypothalamic-pituitary-adrenal SDS = standard deviation score sFC = serum free cortisol TC = total cortisol.
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Kumar M, Kalita J, Tripathi A, Misra UK. Is drug-induced hepatitis related to the severity of tuberculous meningitis? Trans R Soc Trop Med Hyg 2018; 111:520-526. [DOI: 10.1093/trstmh/try006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 01/15/2018] [Indexed: 11/13/2022] Open
Affiliation(s)
- Mritunjai Kumar
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, UP-226014
| | - Jayantee Kalita
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, UP-226014
| | - Abhilasha Tripathi
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, UP-226014
| | - Usha K Misra
- Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, UP-226014
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Verbeeten KC, Ahmet AH. The role of corticosteroid-binding globulin in the evaluation of adrenal insufficiency. J Pediatr Endocrinol Metab 2018; 31:107-115. [PMID: 29194043 DOI: 10.1515/jpem-2017-0270] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Accepted: 11/01/2017] [Indexed: 12/29/2022]
Abstract
Cortisol is a hydrophobic molecule that is largely bound to corticosteroid-binding globulin (CBG) in the circulation. In the assessment of adrenal insufficiency, many clinicians measure a total serum cortisol level, which assumes that CBG is present in normal concentrations and with a normal binding affinity for cortisol. CBG concentration and affinity are affected by a number of common factors including oral contraceptive pills (OCPs), fever and infection, as well as rare mutations in the serine protease inhibitor A6 (SERPINA6) gene, and as such, total cortisol levels might not be the ideal way to assess adrenal function in all clinical circumstances. This paper reviews the limitations of immunoassay and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the measurement of total cortisol, the challenges of measuring free serum cortisol directly as well as the difficulties in calculating an estimated free cortisol from total cortisol, CBG and albumin concentrations. Newer approaches to the evaluation of adrenal insufficiency, including the measurement of cortisol and cortisone in the saliva, are discussed and a possible future role for these tests is proposed.
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Khoo B, Boshier PR, Freethy A, Tharakan G, Saeed S, Hill N, Williams EL, Moorthy K, Tolley N, Jiao LR, Spalding D, Palazzo F, Meeran K, Tan T. Redefining the stress cortisol response to surgery. Clin Endocrinol (Oxf) 2017; 87:451-458. [PMID: 28758231 DOI: 10.1111/cen.13439] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 07/24/2017] [Accepted: 07/25/2017] [Indexed: 11/30/2022]
Abstract
BACKGROUND Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. METHODS Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. RESULTS Ninety-three patients underwent surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P = .0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. CONCLUSIONS The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement.
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Affiliation(s)
- Bernard Khoo
- Endocrinology, Division of Medicine, University College London, Royal Free Hospital, London, UK
| | - Piers R Boshier
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Alexander Freethy
- Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - George Tharakan
- Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Samerah Saeed
- Department of Surgery and Cancer, Imperial College London, St Mary's Hospital, London, UK
| | - Neil Hill
- Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Emma L Williams
- Department of Clinical Biochemistry, North West London Pathology, Charing Cross Hospital, London, UK
| | - Krishna Moorthy
- Department of Surgery, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Neil Tolley
- Department of Surgery, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Long R Jiao
- Department of Surgery, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Duncan Spalding
- Department of Surgery, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Fausto Palazzo
- Department of Endocrine Surgery, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK
| | - Karim Meeran
- Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Tricia Tan
- Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
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Effects of Preoperative Psychological Interventions on Catecholamine and Cortisol Levels After Surgery in Coronary Artery Bypass Graft Patients: The Randomized Controlled PSY-HEART Trial. Psychosom Med 2017; 79:806-814. [PMID: 28846584 DOI: 10.1097/psy.0000000000000483] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE The aim of the study was to examine whether preoperative psychological interventions targeting patients' expectations are capable of influencing the biological stress response after coronary artery bypass graft (CABG) surgery and could thus improve recovery after heart surgery. METHODS Randomized controlled trial with assessments 10 days before surgery, after psychological intervention (day of hospital admission, but before surgery), postoperative (6-8 days later), and at follow-up (6 months after surgery). Eligible patients (N = 124) scheduled for elective on-pump CABG or CABG with valve replacement surgery were approached before hospital admission. Standard medical care (SMC) was compared with two additional preoperative psychological interventions: (a) an expectation manipulation intervention to optimize patients' expectations about course and outcomes or (b) supportive therapy, containing the same amount of therapeutic attention, but without specifically focusing on expectations. Postoperative plasma adrenaline, noradrenaline, and cortisol levels were a secondary outcome of our study (primary outcome patients' disability 6 months after surgery and other secondary patient-reported or clinical outcomes were reported elsewhere). RESULTS Expectation manipulation intervention (3.68 ln pg/mL, 95% confidence interval = 3.38-3.98, p = .015) and supportive therapy (3.70 ln pg/mL, 95% confidence interval = 3.38-4.01, p = .026) led to significantly lower postoperative adrenaline levels compared with SMC (4.26 ln pg/mL, 95% confidence interval = 3.99-4.53) only. There were no treatment effects of the preoperative intervention for noradrenaline (p = .90) or cortisol (p = .30). Higher postoperative adrenaline levels predicted disability 6 months after surgery (r = .258, p = .018). CONCLUSIONS In addition to SMC, preoperative psychological interventions seem to buffer psychobiological stress responses and could thus facilitate recovery from CABG surgery. Patients' postoperative stress responses could be an important factor for explaining trajectories of long-term outcomes. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov(NCT01407055).
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Eyal O, Limor R, Oren A, Schachter-Davidov A, Stern N, Weintrob N. Establishing Normal Ranges of Basal and ACTH-Stimulated Serum Free Cortisol in Children. Horm Res Paediatr 2017; 86:94-99. [PMID: 27437687 DOI: 10.1159/000447946] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 06/22/2016] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Normative data have been established for stimulated serum total cortisol in children but not for serum free cortisol. METHODS Children who were referred for ACTH testing to rule out adrenal insufficiency were enrolled. Only children with normal response and normal androgen levels were included. Total cortisol was determined by a chemiluminescence method, and free cortisol was measured by the same method following equilibrium dialysis. RESULTS The study group consisted of 85 subjects (28 male; 57 female) with a median age of 8.5 years (range 0.6-17.7). The mean basal and peak total cortisol levels were 11.5 ± 5.7 and 32.9 ± 6.2 μg/dl, respectively. The mean basal and peak free cortisol levels were 0.4 ± 0.3 and 1.8 ± 0.6 μg/dl, respectively. There was a negative correlation between peak total cortisol and age but not between peak free cortisol and age. The 3rd and 97th percentile values for peak free cortisol were 0.94 μg/dl (26 nmol/l) and 2.97 μg/dl (82 nmol/l), respectively. CONCLUSIONS Measurement of free cortisol has the advantage of being independent of cortisol-binding globulin levels. This study provides reference ranges for stimulated free cortisol in children, with a cutoff value of 0.9 μg/dl (25 nmol/l) as a normal response to a standard ACTH test.
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Affiliation(s)
- Ori Eyal
- Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
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D’Aurizio F, Tozzoli R, Dorizzi RM, Brescia V, Fortunato A, Porzio O, Vitillo M. La diagnostica di laboratorio delle malattie del surrene. Raccomandazioni pratiche per l’insufficienza surrenalica primaria. LA RIVISTA ITALIANA DELLA MEDICINA DI LABORATORIO - ITALIAN JOURNAL OF LABORATORY MEDICINE 2016; 12:234-242. [DOI: 10.1007/s13631-016-0135-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, Torpy DJ. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101:364-89. [PMID: 26760044 PMCID: PMC4880116 DOI: 10.1210/jc.2015-1710] [Citation(s) in RCA: 1041] [Impact Index Per Article: 115.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. PARTICIPANTS The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. EVIDENCE This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. CONSENSUS PROCESS The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. CONCLUSIONS We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 μg) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (∼8 mg/m(2)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.
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Affiliation(s)
- Stefan R Bornstein
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Bruno Allolio
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Wiebke Arlt
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Andreas Barthel
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Andrew Don-Wauchope
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Gary D Hammer
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Eystein S Husebye
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Deborah P Merke
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - M Hassan Murad
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - Constantine A Stratakis
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
| | - David J Torpy
- Medizinische Klinik und Poliklinik III (S.R.B., A.B.), Universitätsklinikum Dresden, 01307 Dresden, Germany; Department of Endocrinology and Diabetes (S.R.B.), King's College London, London WC2R 2LS, United Kingdom; Department of Internal Medicine I (B.A.), Endocrine and Diabetes Unit, University Hospital Würzburg, 97080 Würzburg, Germany; Comprehensive Heart Failure Center (B.A.), University of Würzburg, 97080 Würzburg, Germany; Centre for Endocrinology, Diabetes, and Metabolism (W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; Endokrinologikum Ruhr (A.B.), 44866 Bochum, Germany; Department of Pathology and Molecular Medicine (A.D.-W.), McMaster University, Hamilton, ON L8S 4L8, Canada; Hamilton Regional Laboratory Medicine Program (A.D.-W.), Hamilton, ON L8N 4A6, Canada; Department of Internal Medicine (G.D.H.), Division of Metabolism, Endocrinology, and Diabetes, and Cancer Center, University of Michigan, Ann Arbor, Michigan 48109; Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital (E.S.H.), 5021 Bergen, Norway; National Institutes of Health Clinical Center (D.P.M.), Bethesda, Maryland 20814; Mayo Clinic, Division of Preventive Medicine (M.H.M.), Rochester, Minnesota 55905; Eunice Kennedy Shriver National Institute of Child Health and Human Development (C.A.S.), National Institutes of Health, Bethesda, Maryland 20892; and Endocrine and Metabolic Unit (D.J.T.), Royal Adelaide Hospital, University of Adelaide, Adelaide SA 5000, Australia
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Bancos I, Erickson D, Bryant S, Hines J, Nippoldt TB, Natt N, Singh R. PERFORMANCE OF FREE VERSUS TOTAL CORTISOL FOLLOWING COSYNTROPIN STIMULATION TESTING IN AN OUTPATIENT SETTING. Endocr Pract 2015; 21:1353-63. [PMID: 26340138 DOI: 10.4158/ep15820.or] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Free cortisol (FC) is potentially superior to total cortisol (TC) measurements in selected clinical settings; however, the advantages of uniform use of FC in outpatient settings are unclear. The objectives of this study were to describe the dynamic response of FC during cosyntropin stimulation testing (CST) compared to TC and to determine the rates of discordance. METHODS This is a cross-sectional study of 295 stable patients who underwent CST in an outpatient Endocrine Testing Center. The main outcome measures were TC and FC measurements during CST. RESULTS The mean age of the 295 subjects was 49.1 (16.9) years. Of 218 females, 43 were taking estrogen therapy (ET) at the time of testing. Adrenal insufficiency (AI) was diagnosed in 41/295 (14%) patients. The FC concentrations were associated with TC concentrations at baseline (R(2) = 0.77, P<.001), 30 minutes (R(2) = 0.87, P<.001), and 60 minutes (R(2) = 0.90, P<.001). The FC cutoffs for AI were 873 and 1,170 ng/dL at 30 and 60 minutes, respectively. The FC had a more pronounced fold change from baseline to peak than TC (median 3.2 vs. 1.7, P<.001). Both TC and FC at baseline were higher in females on ET compared to those who were not and to males; however, peak TC and FC values were similar. In 3/43 females on ET, FC, and TC results were discordant (P = .003). CONCLUSION We report 99% concordance of TC and FC measurements in a large outpatient cohort. The discordant rates were high in females treated with ET (7%). The FC measurements during CST in females on ET may provide a more rapid and accurate diagnosis of AI.
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Karagiannis AKA, Nakouti T, Pipili C, Cholongitas E. Adrenal insufficiency in patients with decompensated cirrhosis. World J Hepatol 2015; 7:1112-1124. [PMID: 26052400 PMCID: PMC4450188 DOI: 10.4254/wjh.v7.i8.1112] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/12/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal (HPA) axis are causes for adrenal insufficiency (AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics as well. Both stable cirrhotics and liver transplant patients (early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels (the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI.
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Tabatabaei N, Rodd CJ, Kremer R, Weiler HA. Osteocalcin, but not deoxypyridinoline, increases in response to isoflurane-induced anaesthesia in young female guinea pigs. J Bone Miner Metab 2015; 33:253-60. [PMID: 24858976 DOI: 10.1007/s00774-014-0593-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2013] [Accepted: 04/09/2014] [Indexed: 01/26/2023]
Abstract
The effect of the inhaled anaesthetic isoflurane was investigated on bone biomarkers, both during maturation and on minerals and glucose postpartum. Female guinea pigs (n = 10) were anaesthetized during maturation (5 and 9 weeks) and postpartum (26 weeks of age) with isoflurane during dual-energy X-ray absorptiometry scanning. Blood collection was performed at all ages before and after anaesthesia for measurement of plasma osteocalcin (OC), total deoxypyridinoline (tDPD), and cortisol. Postpartum measurements also included: blood ions, acid-base parameters and glucose, plasma minerals, total alkaline phosphatase (tALP), and albumin. Plasma OC concentration almost doubled after exposure to isoflurane at 5 weeks (30.1 ± 5.0-57.9 ± 11.2 nmol/L, p < 0.001) and at 9 weeks (29.1 ± 7.5-62.9 ± 15.9 nmol/L, p < 0.001), but did not change postpartum (3.7 ± 3.3-4.3 ± 3.9 nmol/L, p = 0.88). There was no effect of isoflurane exposure on plasma tDPD at any age. Plasma cortisol increased after exposure to isoflurane at 9 weeks (1859.6 ± 383.2-2748.0 ± 235.3 nmol/L, p < 0.01) and postpartum (3376.7 ± 322.2-4091.6 ± 195.6 nmol/L, p < 0.001) but not at 5 weeks (2088.3 ± 326.4-2464.1 ± 538.0 nmol/L, p > 0.05). Blood ionized Ca(2+), Na(+) and plasma total Ca did not change, whereas plasma albumin decreased, and inorganic phosphate (PO4) and Cl(-) increased upon exposure to isoflurane. Isoflurane decreased tALP (43.2 ± 6.6-40.2 ± 5.9 IU/L, p = 0.01) and increased glucose (7.5 ± 0.6-10.9 ± 1.7 mmol/L, p < 0.0001) postpartum. Isoflurane inflates the assessment of a bone-derived biomarker, OC, during rapid growth, but not following pregnancy when formation is very low. Measurements prior to anaesthesia are recommended to reflect normal metabolism.
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Affiliation(s)
- Negar Tabatabaei
- School of Dietetics and Human Nutrition, Macdonald-Stewart Building Macdonald Campus, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, Quebec, H9X 3V9, Canada
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Elbuken G, Tanriverdi F, Karaca Z, Kula M, Gokahmetoglu S, Unluhizarci K, Kelestimur F. Comparison of salivary and calculated free cortisol levels during low and standard dose of ACTH stimulation tests in healthy volunteers. Endocrine 2015; 48:439-43. [PMID: 25115637 DOI: 10.1007/s12020-014-0378-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 08/01/2014] [Indexed: 10/24/2022]
Abstract
Salivary cortisol (SC) has been increasingly used as a surrogate biomarker of free cortisol (FC) for the assessment of hypothalamo-pituitary-adrenal (HPA) axis, but there are not enough data regarding its use during ACTH stimulation tests. Therefore, we aimed to determine the responses of SC, calculated free cortisol (cFC) and free cortisol index (FCI) to ACTH stimulation tests in healthy adults. Forty-four healthy volunteers (24 men and 20 women) were included in the study. Low-dose (1 µg) and standard-dose (250 µg) ACTH stimulation tests were performed on two consecutive days. Basal and stimulated total cortisol (TC) and cortisol-binding globulin (CBG) levels and SC levels were measured during both doses of ACTH stimulation tests. cFC (by Coolens' equation) and FCI levels were calculated from simultaneously measured TC and CBG levels. The minimum SC, cFC, FCI levels after low-dose ACTH stimulation test were 0.21, 0.33, 16.06 µg/dL, and after standard-dose ACTH were 0.85, 0.46, 26.11 µg/dL, respectively, in healthy individuals who all had TC responses higher than 20 µg/dL. Peak CBG levels after both doses of ACTH stimulation tests were found to be higher in women than in men. So, by its effect, peak cFC and FCI levels were found to be lower in female than in male group. Neither TC nor SC levels were affected by gender. cFC and FCI levels depend on CBG levels and they are affected by gender. Cut-off levels for SC, cFC, FCI levels after both low- and standard-dose ACTH stimulation are presented. Studies including patients with adrenal insufficiency would be helpful to see the diagnostic value of these suggested cut-off levels.
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Lennartsson AK, Sjörs A, Währborg P, Ljung T, Jonsdottir IH. Burnout and Hypocortisolism - A Matter of Severity? A Study on ACTH and Cortisol Responses to Acute Psychosocial Stress. Front Psychiatry 2015; 6:8. [PMID: 25698980 PMCID: PMC4313581 DOI: 10.3389/fpsyt.2015.00008] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Accepted: 01/16/2015] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Common consequences of long-term psychosocial stress are fatigue and burnout. It has been suggested that burnout could be associated with hypocortisolism, thus, inability to produce sufficient amounts of cortisol. This study aimed to investigate whether patients with clinical burnout exhibit aberrant ACTH and cortisol responses under acute psychosocial stress compared with healthy individuals. METHODS Nineteen patients (9 men and 10 women) and 37 healthy subjects (20 men and 17 women), underwent the Trier Social Stress Test. Blood samples and saliva samples were collected before, after, and during the stress test for measurements of plasma ACTH, serum cortisol, and salivary cortisol. Several statistical analyses were conducted to compare the responses between patients and controls. In addition, in order to investigate the possibility that burnout patients with more severe symptoms would respond differently, sub-groups of patients reporting higher and lower burnout scores were compared. RESULTS In both patients and healthy controls, we observed elevated levels of ACTH and cortisol after exposure to the stressor. There were no differences in responses of ACTH, serum cortisol, or salivary cortisol between patients and controls. Patients reporting higher burnout scores had lower salivary cortisol responses than controls, indicating that patients with more severe burnout symptoms may be suffering from hypocortisolism. In addition, patients with more severe burnout symptoms tended to have smaller ACTH responses than the other patients. However, there was no corresponding difference in serum cortisol. CONCLUSION This study indicates that hypocortisolism is not present in a clinical burnout patient group as a whole but may be present in the patients with more severe burnout symptoms.
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Affiliation(s)
| | - Anna Sjörs
- The Institute of Stress Medicine , Gothenburg , Sweden
| | - Peter Währborg
- Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Thomas Ljung
- Department of Health Sciences, Mid Sweden University , Östersund , Sweden
| | - Ingibjörg H Jonsdottir
- The Institute of Stress Medicine , Gothenburg , Sweden ; The Department of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
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Balbão VMP, Costa MMA, Castro M, Carlotti APCP. Evaluation of adrenal function in critically ill children. Clin Endocrinol (Oxf) 2014; 81:559-65. [PMID: 24588209 DOI: 10.1111/cen.12444] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 01/03/2014] [Accepted: 02/25/2014] [Indexed: 12/15/2022]
Abstract
OBJECTIVE There is no consensus on adequate adrenal response to critical illness. We aimed to evaluate adrenal function in critically ill children and its association with clinical outcome. We hypothesized that salivary cortisol would be a more appropriate tool to evaluate adrenal function in critically ill children. METHODS This was a prospective cohort study. The concentrations of serum total and salivary cortisol were measured in 34 critically ill children before and after stimulation with 250 μg adrenocorticotropic hormone (ACTH), and values were compared to a control group of healthy children (n = 15). Association between outcome and adrenal insufficiency defined by an increment in serum cortisol ≤250 nm (9 μg/dl) post-ACTH was assessed. RESULTS Serum total and salivary cortisol concentrations pre- and post-ACTH were significantly higher in patients, and they were correlated at baseline (r = 0·67; P < 0·0001) and after ACTH (r = 0·41; P = 0·02). The incidence of adrenal insufficiency was 32·3%. This group had higher Paediatric Risk of Mortality III score (P = 0·04) but Paediatric Logistic Organ Dysfunction and vasoactive inotropic scores, duration of mechanical ventilation and length of paediatric intensive care unit and hospital stay were not significantly different compared with those with an increment >250 nm (9 μg/dl) post-ACTH. An inverse correlation between salivary cortisol post-ACTH and vasoactive inotropic score (r = -0·56; P = 0·0008) was observed. A salivary cortisol concentration post-ACTH of ≤226 nm (8·2 μg/dl) had a sensitivity of 79% and a specificity of 62% to discriminate need for vasoactive or inotropic support (area under receiver operating characteristic (ROC) curve 0·74). CONCLUSION Adrenal insufficiency defined by the 'delta criterion' was not associated with outcome. A post-ACTH salivary cortisol of ≤226 nm (8·2 μg/dl) may be suggestive of an insufficient adrenal response to critical illness.
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Affiliation(s)
- Viviane M P Balbão
- Department of Paediatrics, Division of Paediatric Critical Care, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil
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Abstract
OBJECTIVE Ghrelin, a peptide hormone secreted mainly by the stomach, increases appetite and food intake. Surprisingly, ghrelin levels are lower in obese individuals with binge eating disorder (BED) than in obese non-BED individuals. Acute psychological stress has been shown to raise ghrelin levels in animals and humans. Our aim was to assess ghrelin levels after a cold pressor test (CPT) in women with BED. We also examined the relationship between the cortisol stress response and changes in ghrelin levels. METHODS Twenty-one obese (mean [standard deviation] body mass index = 34.9 [5.8] kg/m(2)) women (10 non-BED, 11 BED) underwent the CPT, hand submerged in ice water for 2 minutes. Blood samples were drawn for 70 minutes and assayed for ghrelin and cortisol. RESULTS There were no differences between the groups in ghrelin levels at baseline (-10 minutes). Ghrelin rose significantly after the CPT (F = 2.4, p = .024) peaking at 19 minutes before declining (F = 17.9, p < .001), but there were no differences between the BED and non-BED groups. Area under the curve for ghrelin was not related to ratings of pain, stress, hunger, or desire to eat after CPT. In addition, there were no observed relationships between the area under the curves for ghrelin or cortisol after stress. CONCLUSIONS Although there were no differences between BED groups, there was a significant rise in ghrelin in obese humans after a stressor, consistent with other recent reports suggesting a stress-related role for ghrelin.
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Kaushik A, Vasudev A, Arya SK, Pasha SK, Bhansali S. Recent advances in cortisol sensing technologies for point-of-care application. Biosens Bioelectron 2013; 53:499-512. [PMID: 24212052 DOI: 10.1016/j.bios.2013.09.060] [Citation(s) in RCA: 176] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 09/14/2013] [Accepted: 09/17/2013] [Indexed: 10/26/2022]
Abstract
Everyday lifestyle related issues are the main cause of psychological stress, which contributes to health disparities experienced by individuals. Prolonged exposure to stress leads to the activation of signaling pathways from the brain that leads to release of cortisol from the adrenal cortex. Various biomarkers have been affected by psychological stress, but cortisol "a steroid hormone" is known as a potential biomarker for its estimation. Cortisol can also be used as a target analyte marker to determine the effect of exposure such as organophosphates on central nervous system, which alters the endocrine system, leading to imbalance in cortisol secretion. Cortisol secretion of individuals depends on day-night cycle and field environment hence its detection at point-of-care (POC) is deemed essential to provide personalized healthcare. Chromatographic techniques have been traditionally used to detect cortisol. The issues relating to assay formation, system complexity, and multistep extraction/purification limits its application in the field. In order to overcome these issues and to make portable and effective miniaturized platform, various immunoassays sensing strategies are being explored. However, electrochemical immunosensing of cortisol is considered as a recent advancement towards POC application. Highly sensitive, label-free and selective cortisol immunosensor based on microelectrodes are being integrated with the microfluidic system for automated diurnal cortisol monitoring useful for personalized healthcare. Although the reported sensing devices for cortisol detection may have a great scope to improve portability, electronic designing, performance of the integrated sensor, data safety and lifetime for point-of-care applications, This review is an attempt to describe the various cortisol sensing platforms and their potential to be integrated into a wearable system for online and continuous monitoring of cortisol rhythm at POC as a function of one's environment.
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Affiliation(s)
- Ajeet Kaushik
- Bio-MEMS and Microsystems Laboratory, Department of Electrical and Computer Engineering, Florida International University, Miami, FL 33174, United States.
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Trevisi E, Bertoni G, Lombardelli R, Minuti A. Relation of inflammation and liver function with the plasma cortisol response to adrenocorticotropin in early lactating dairy cows. J Dairy Sci 2013; 96:5712-22. [DOI: 10.3168/jds.2012-6375] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Accepted: 05/19/2013] [Indexed: 01/06/2023]
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Park CS, Guilleminault C, Hwang SH, Jeong JH, Park DS, Maeng JH. Correlation of salivary cortisol level with obstructive sleep apnea syndrome in pediatric subjects. Sleep Med 2013; 14:978-84. [PMID: 23891237 DOI: 10.1016/j.sleep.2013.05.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Revised: 05/18/2013] [Accepted: 05/25/2013] [Indexed: 11/24/2022]
Abstract
OBJECTIVE Obstructive sleep apnea syndrome (OSAS) is associated with stress system activation involving the hypothalamic-pituitary-adrenocortical (HPA) axis. The relationships among salivary cortisol, a measure of the HPA axis, and objective parameters of polysomnography (PSG) and subjective sleep symptoms were examined. METHODS Our prospective study enrolled 80 children who had a physical examination, underwent overnight PSG, and completed the Korean version of the modified pediatric Epworth sleepiness scale (KMPESS) and OSA-18 (KOSA-18) questionnaires. Saliva was collected at night before PSG and in the early morning after PSG. RESULTS Subjects (N=80) were divided into control (n=32, apnea-hypopnea index [AHI]<1) and OSAS (n=48, AHI > or =1) groups; the OSAS group was subdivided into mild (1< or = AHI < 5) and moderate to severe (AHI > or =5) groups. Although salivary cortisol before PSG (n-sCor) did not show a significant change with OSAS severity, salivary cortisol after PSG (m-sCor) significantly decreased with OSAS severity. This decrease resulted in a salivary cortisol ratio (r-sCor) that was significantly different between the control group and the two OSAS subgroups. The m-sCor and sub-sCor of the total group as well as the m-sCor, sub-sCor, and r-sCor of the OSAS group were negatively related to the oxygen desaturation index (ODI). The m-sCor and r-sCor in the OSAS group also were related to subjective sleep symptoms (quality of life [QOL] by KOSA-18). CONCLUSIONS Among the four salivary cortisol parameters, r-sCor was negatively associated with OSAS severity, ODI, and QOL (KOSA-18), which may indicate a chronically stressed HPA axis. These results demonstrate that salivary cortisol may be a useful biomarker of OSAS.
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Affiliation(s)
- Chan-Soon Park
- Department of Otolaryngology-Head and Neck Surgery, St. Vincent's Hospital, The Catholic University of Korea, College of Medicine, Suwon, Republic of Korea
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Trifan A, Chiriac S, Stanciu C. Update on adrenal insufficiency in patients with liver cirrhosis. World J Gastroenterol 2013; 19:445-456. [PMID: 23382623 PMCID: PMC3558568 DOI: 10.3748/wjg.v19.i4.445] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 12/03/2012] [Accepted: 12/20/2012] [Indexed: 02/06/2023] Open
Abstract
Liver cirrhosis is a major cause of mortality worldwide, often with severe sepsis as the terminal event. Over the last two decades, several studies have reported that in septic patients the adrenal glands respond inappropriately to stimulation, and that the treatment with corticosteroids decreases mortality in such patients. Both cirrhosis and septic shock share many hemodynamic abnormalities such as hyperdynamic circulatory failure, decreased peripheral vascular resistance, increased cardiac output, hypo-responsiveness to vasopressors, increased levels of proinflammatory cytokines [interleukine(IL)-1, IL-6, tumor necrosis factor-alpha] and it has, consequently, been reported that adrenal insufficiency (AI) is common in critically ill cirrhotic patients. AI may also be present in patients with stable cirrhosis without sepsis and in those undergoing liver transplantation. The term hepato-adrenal syndrome defines AI in patients with advanced liver disease with sepsis and/or other complications, and it suggests that it could be a feature of liver disease per se, with a different pathogenesis from that of septic shock. Relative AI is the term given to inadequate cortisol response to stress. More recently, another term is used, namely "critical illness related corticosteroid insufficiency" to define "an inadequate cellular corticosteroid activity for the severity of the patient's illness". The mechanisms of AI in liver cirrhosis are not completely understood, although decreased levels of high-density lipoprotein cholesterol and high levels of proinflammatory cytokines and circulatory endotoxin have been suggested. The prevalence of AI in cirrhotic patients varies widely according to the stage of the liver disease (compensated or decompensated, with or without sepsis), the diagnostic criteria defining AI and the methodology used. The effects of corticosteroid therapy on cirrhotic patients with septic shock and AI are controversial. This review aims to summarize the existing published information regarding AI in patients with liver cirrhosis.
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Dalegrave D, Silva RL, Becker M, Gehrke LV, Friedman G. Relative adrenal insufficiency as a predictor of disease severity and mortality in severe septic shock. Rev Bras Ter Intensiva 2012; 24:362-8. [PMID: 23917934 PMCID: PMC4031805 DOI: 10.1590/s0103-507x2012000400012] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2012] [Accepted: 12/04/2012] [Indexed: 01/27/2023] Open
Abstract
OBJECTIVE To evaluate if cortisol responses to 250 µg of intravenously administered adrenocorticotropic hormone are related to disease severity and, hence, mortality. METHODS This is a retrospective study in a medical-surgical intensive care unit of a university hospital. We studied 69 consecutive patients with septic shock over a 1-yr period; these patients underwent a short 250-µg adrenocorticotropic hormone test because they exhibited >6 hours of progressive hemodynamic instability requiring repeated fluid challenges and vasopressor treatment to maintain blood pressure. The test was performed by intravenously injecting 250 µg of synthetic adrenocorticotropic hormone and measuring cortisol immediately before injection, 30 minutes post-injection and 60 minutes post-injection. RESULTS The mean APACHE II score was 22±7. The intensive care unit mortality rate at day 28 was 55%. Median baseline cortisol levels (19 [11-27] µg/dL versus 24 [18-34] µg/dL, p=0.047) and median baseline cortisol/albumin ratios (7.6 [4.6-12.3] versus 13.9 [8.8-18.5]; p=0.01) were lower in survivors than in non-survivors. Responders and non-responders had similar baseline clinical data and outcomes. The variables that were significantly correlated with outcome based on the area under the ROC curves (AUC) were APACHE II (AUC=0.67 [0.535 to 0.781]), baseline cortisol (µg/dl) (AUC=0.662 [0.536 to 0.773], peak cortisol (µg/dl) (AUC=0.642 [0.515 to 0.755]) and baseline cortisol/albumin (AUC=0.75 [0.621 to 0.849]). CONCLUSIONS Increased basal cortisol is associated with mortality and disease severity. Cortisol responses upon adrenocorticotropic hormone stimulation were not related to outcome. The cortisol/albumin ratio does not predict unfavorable outcomes better than total cortisol levels or help to improve the accuracy of the adrenocorticotropic hormone test.
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Affiliation(s)
- Daniele Dalegrave
- Central Intensive Care Unit, Complexo Hospitalar Santa Casa - Porto
Alegre (RS), Brazil
| | - Rafael Lockshin Silva
- Central Intensive Care Unit, Complexo Hospitalar Santa Casa - Porto
Alegre (RS), Brazil
| | - Maicon Becker
- Central Intensive Care Unit, Complexo Hospitalar Santa Casa - Porto
Alegre (RS), Brazil
| | - Lísia Varella Gehrke
- Central Intensive Care Unit, Complexo Hospitalar Santa Casa - Porto
Alegre (RS), Brazil
| | - Gilberto Friedman
- Central Intensive Care Unit, Complexo Hospitalar Santa Casa - Porto
Alegre (RS), Brazil
- Universidade Federal do Rio Grande do Sul-UFRGS - Porto Alegre
(RS), Brazil
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Yamaguchi M, Matsuda Y, Sasaki S, Sasaki M, Kadoma Y, Imai Y, Niwa D, Shetty V. Immunosensor with fluid control mechanism for salivary cortisol analysis. Biosens Bioelectron 2012; 41:186-91. [PMID: 22939507 DOI: 10.1016/j.bios.2012.08.016] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2012] [Revised: 07/20/2012] [Accepted: 08/07/2012] [Indexed: 10/28/2022]
Abstract
The purpose of this research is to demonstrate a new design for a cortisol immunosensor for the noninvasive and quantitative analysis of salivary cortisol. We propose a cortisol immunosensor with a fluid control mechanism which has both a vertical flow and a lateral flow. The detected current resulting from a competitive reaction between the sample cortisol and a glucose oxidase (GOD)-labeled cortisol conjugate was found to be inversely related to the concentration of cortisol in the sample solution. A calibration curve using the relative detected current showed a R(2)=0.98 and CV=14% for a range of standard cortisol solutions corresponding to the concentrations of native salivary cortisol (0.1-10 ng/ml). The measurement could be accomplished within 35 min and the cortisol immunosensor could be reused. These results show promise for realizing an on-site and easy-to-use biosensor for cortisol. Used for evaluation of human salivary cortisol levels, the cortisol immunosensor measurement corresponded closely with commercially available ELISA method (R(2)=0.92). Our results indicate the promise of the new cortisol immunosensor for noninvasive, point of care measurement of human salivary cortisol levels.
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Affiliation(s)
- Masaki Yamaguchi
- Biomedical Engineering & Robotics Laboratory, Graduate School of Engineering, Iwate University, 4-3-5 Ueda, Morioka 020-8551, Japan.
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Martin C, Steinke T, Bucher M, Raspé C. [Perioperative Addisonian crisis]. Anaesthesist 2012; 61:503-11. [PMID: 22695777 DOI: 10.1007/s00101-012-2033-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2011] [Revised: 04/02/2012] [Accepted: 04/19/2012] [Indexed: 10/28/2022]
Abstract
An Addisonian crisis marks an acute adrenocortical failure which can be caused by decompensation of a chronic insufficiency due to stress, an infarct or bleeding of the adrenal cortex and also abrupt termination of a long-term glucocorticoid medication. This article reports the case of a 25-year-old patient with Crohn's disease who suffered an Addisonian crisis with hypotension, hyponatriemia and hypoglycemia during an emergency laparotomy after he had terminated prednisolone medication on his own authority. This necessitated an aggressive volume therapy in addition to an initial therapy with 100 mg hydrocortisone, 8 g glucose and a continuous administration of catecholamines. Under this treatment regimen hemodynamic stabilization was achieved. Reduction of the administration of hydrocortisone after 3 days resulted in cardiovascular insufficiency which required an escalation of the hydrocortisone substitution.
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Affiliation(s)
- C Martin
- Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle, Deutschland.
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Vanaelst B, De Vriendt T, Huybrechts I, Rinaldi S, De Henauw S. Epidemiological approaches to measure childhood stress. Paediatr Perinat Epidemiol 2012; 26:280-97. [PMID: 22471688 DOI: 10.1111/j.1365-3016.2012.01258.x] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The prevalence of childhood stress has repeatedly been shown to be high, with 'parental separation' and 'being bullied at school' as the most frequently reported stressors in the child's everyday life. This is quite alarming as children are most vulnerable to the adverse psychological and physiological health consequences of chronic stress exposure. Despite growing research interest in this field over the last years, literature falls short in providing an overview of methods to adequately assess stress in elementary school children (6-12 years old). This review describes questionnaires and interviews, as well as laboratory measurements of cortisol in biological samples (serum, urine, saliva and hair) as stress assessment methods in children, with the emphasis on epidemiological research settings. Major characteristics, strengths and limitations of these methods are established, examples of child-specific stressor questionnaires and interviews are provided and specific recommendations with respect to epidemiological research are formulated. In addition, hair cortisol as a potential biomarker for chronic stress (in children) is discussed more thoroughly. This review is meant to serve as a preliminary guide for health researchers new to this research area by reflecting on theoretical and methodological aspects in childhood stress assessment.
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Affiliation(s)
- Barbara Vanaelst
- Department of Public Health, Ghent University, University Hospital, De Pintelaan 185, Ghent, Belgium.
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Limor R, Tordjman K, Marcus Y, Greenman Y, Osher E, Sofer Y, Stern N. Serum free cortisol as an ancillary tool in the interpretation of the low-dose 1-μg ACTH test. Clin Endocrinol (Oxf) 2011; 75:294-300. [PMID: 21535070 DOI: 10.1111/j.1365-2265.2011.04080.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Serum free cortisol, rather than serum total cortisol (TC), determines glucocorticoid activity in vivo, but how the considerable inter-subject variation in ambient serum free cortisol affects the outcome of dynamic hypothalamic-pituitary-adrenal (HPA) assessment in noncritically ill subjects is unknown. DESIGN, PATIENTS AND MEASUREMENTS We performed the low-dose 1-μg ACTH test in 75 subjects referred for HPA evaluation. Serum TC was determined by a chemiluminescence method, and serum free cortisol was measured by the same method following equilibrium dialysis. In a subset of these patients, salivary cortisol was also measured. RESULTS Mean fraction of free cortisol was 5·07 ± 4·08% (±SD; range 1·77-10·1%). Although no correlation was seen between TC and the fraction (%) of free serum cortisol, a positive correlation existed between baseline total and free cortisol (R = 0·539 P = 0·01), as well as between peak ACTH-stimulated total and free cortisol (R = 0·619; P = 0·01). There was no correlation between baseline salivary cortisol and serum free cortisol and between peak ACTH-stimulated salivary and serum free cortisol. Using the lowest attained peak serum free cortisol in subjects whose TC response to ACTH was normal (≥ 500 nM), the minimal 'pass' level for normal serum free cortisol response to 1 μg ACTH was set at 25·0 nM. Five of the 19 subjects showing subnormal TC response to 1 μg ACTH had normal serum free cortisol response. CONCLUSIONS Discrepancies between the peak free and TC were noted mostly for subjects whose ACTH-stimulated TC peaked between 440 and 580 nm. At this range, the measurement of serum free cortisol allows further refinement of the assessment of borderline responses to 1-μg ACTH.
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Affiliation(s)
- Rona Limor
- Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Molenaar N, Johan Groeneveld AB, Dijstelbloem HM, de Jong MFC, Girbes ARJ, Heijboer AC, Beishuizen A. Assessing adrenal insufficiency of corticosteroid secretion using free versus total cortisol levels in critical illness. Intensive Care Med 2011; 37:1986-93. [PMID: 21850531 DOI: 10.1007/s00134-011-2342-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2011] [Accepted: 06/25/2011] [Indexed: 12/13/2022]
Abstract
PURPOSE To study the value of free versus total cortisol levels in assessing relative adrenal insufficiency during critical illness-related 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 μg) 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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Affiliation(s)
- Nienke Molenaar
- Department of Intensive Care, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands
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Abstract
OBJECTIVE The pathophysiology of low-cardiac-output syndrome after cardiopulmonary bypass is incompletely understood, but adrenal insufficiency has been proposed as a contributing factor. Our objective was to examine the effect of cardiopulmonary bypass on the hypothalamic-pituitary-adrenal axis, specifically adrenal responsiveness, in patients with congenital heart disease undergoing surgery. We hoped to correlate bound and free cortisol values both postoperatively and after adrenocorticotropic hormone stimulation, in conjunction with corticosteroid-binding globulin levels, with clinical outcomes to determine whether these variables are sensitive indicators of adrenal axis function. DESIGN Prospective cohort study. SETTING A children's hospital. PATIENTS Fifty-two pediatric heart surgery patients undergoing cardiopulmonary bypass. INTERVENTION Total cortisol and corticosteroid-binding globulin levels were obtained pre- and postoperatively and after a postoperative cosyntropin stimulation test. Free cortisol was calculated by using Coolens' method. MEASUREMENTS AND MAIN RESULTS Nine of 51 (17.6%) patients had low (<3 μg/dL) baseline postoperative total cortisol, median 1.6 μg/dL, yet all nine had normal (>9 μg/dL increase from postoperative baseline) stimulation tests. The corticosteroid-binding globulin levels declined from a mean of 29 mg/L preoperatively to 22 mg/L postoperatively (p < .001) and showed marked variability between patients. Patients with free cortisol δ >6 μg/dL (n = 18, 35%) had a longer length of stay (median 9 vs. 5 days; p = .002), higher inotrope scores (median 13.3 vs. 10.8; p = .05), greater fluid requirement (median 73.5 vs. 55.6 mL/kg; p = .007), and longer ventilator times (median 41.5 vs. 20 hrs; p = .013). CONCLUSIONS Although hypothalamic-pituitary-adrenal axis dysfunction may play a role in low-cardiac-output syndrome among children undergoing congenital heart surgery, using total cortisol to investigate such dysfunction may be inadequate. Decreased corticosteroid-binding globulin levels and marked free cortisol increase after stimulation were associated with worse clinical outcomes. Further investigation into the cortisol-corticosteroid-binding globulin complex and its relationship to free cortisol is necessary to examine the problem of adrenal insufficiency from a more integrated perspective.
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Thevenot T, Borot S, Remy-Martin A, Sapin R, Cervoni JP, Richou C, Vanlemmens C, Cleau D, Muel E, Minello A, Tirziu S, Penfornis A, Di Martino V, Monnet E. Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol. Liver Int 2011; 31:425-433. [PMID: 21281437 DOI: 10.1111/j.1478-3231.2010.02431.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Because over 90% of serum cortisol is bound to albumin and corticosteroid-binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum-free and salivary cortisol concentrations. METHODS We assessed basal (T₀) and post-synacthen (T₆₀) serum total cortisol, serum-free and salivary cortisol in 125 consecutive cirrhotics (95 non-septic and 30 septic patients with a Child>8). RESULTS Serum total cortisol levels significantly decreased from the Child A-C non-septic group, as did albumin and CBG levels, with a non-significant rise in serum-free cortisol concentrations. Non-septic patients with low albumin (≤25 g/L) or CBG levels (≤35 mg/L) had lower T₀ serum total cortisol levels than patients with near-normal albumin (303.4 vs. 382.6 nmol/L; P=0.0035) or with normal CBG levels (289.9 vs. 441.4 nmol/L; P<0.0001), respectively, despite similar serum-free cortisol or salivary cortisol concentrations. Subnormal T₆₀ serum total cortisol concentrations (<510.4 nmol/L) were measured in 7.2% of all patients (Child C: 14.5% vs. Child A and B: 0%; P=0.0013) but no patients exhibited symptoms suggesting adrenal insufficiency. Patients with or without subnormal T₆₀ total cortisol had similar T₀ salivary cortisol and serum-free cortisol concentrations. A trend was observed towards high serum-free cortisol concentrations and mortality in multivariate analysis. CONCLUSIONS Serum total cortisol levels overestimated the prevalence of adrenal dysfunction in cirrhotics with end-stage liver disease. Since serum-free cortisol cannot be measured routinely, salivary cortisol testing could represent a useful approach but needs to be standardized.
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Affiliation(s)
- Thierry Thevenot
- Service d'Hépatologie et de Soins Intensifs Digestifs, Hôpital Jean Minjoz, Besançon cedex, France.
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Fede G, Spadaro L, Tomaselli T, Privitera G, Piro S, Rabuazzo AM, Sigalas A, Xirouchakis E, O'Beirne J, Garcovich M, Tsochatzis E, Purrello F, Burroughs AK. Assessment of adrenocortical reserve in stable patients with cirrhosis. J Hepatol 2011; 54:243-250. [PMID: 21056503 DOI: 10.1016/j.jhep.2010.06.034] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2010] [Revised: 06/16/2010] [Accepted: 06/17/2010] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS Adrenal insufficiency (AI) is reported in critically ill patients with cirrhosis and is associated with increased mortality. It is unclear if AI is an underlying condition or triggered by critical events (e.g. sepsis). We investigated AI in cirrhosis without infection or hemodynamic instability. METHODS A total of 101 consecutive patients with cirrhosis were studied. AI was defined by a total serum cortisol (TC) <18 μg/dl at 20 or 30 min after injection of 1 μg of tetracosactrin. Transcortin, calculated free cortisol (cFC), and free cortisol index (FCI) were assessed in a subgroup of 41 patients, with FCI>12 representing normal adrenal function. RESULTS AI was present in 38 patients (38%). Child score (median, 10 vs 7, p<0.0001), MELD score (median, 17 vs 12, p<0.0001), ascites (68% vs 37%, p<0.01), basal TC (median,7.6 vs 14.9 μg/dl, p<0.001), albumin (28 ± 0.8 vs 33 ± 0.7 g/L, p<0.0001), INR (median, 1.6 vs 1.2, p<0.0001), total bilirubin (median, 51 vs 31 μmol/L, p<0.05), total cholesterol (median, 120 vs 142, p<0.05), and LDL (median, 76 vs 81, p<0.05) were significantly different between those with and without AI. ROC curves showed a basal TC ≤ 12.8 μg/dl to be a cut-off value closely associated with AI. The cFC was significantly related to TC for baseline values (R=0.94, p<0.0001), peak values (R=0.90, p<0.0001), and delta values (R=0.95, p<0.0001), in patients with and without AI. However, no patient had a FCI<12. CONCLUSIONS AI defined by an abnormal response to 1 μg tetracosactrin is frequent in stable patients with cirrhosis, in the absence of infections or hemodynamic instability and is related to the severity of liver disease. However, evaluation of the true incidence of AI should comprise direct assays of free cortisol. Clinical consequences of AI need to be explored.
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Affiliation(s)
- Giuseppe Fede
- Internal Medicine, University of Catania - Garibaldi Hospital, Catania, Italy
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