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Measurements of Serum Free Cortisol in Critically Ill Patients
Open accessAbstract
BACKGROUND: Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone. We investigated the effect of decreased amounts of cortisol-binding proteins on serum total and free cortisol concentrations during critical illness, when glucocorticoid secretion is maximally stimulated. METHODS: Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter). RESULTS: Base-line and cosyntropin-stimulated serum total cortisol concentrations were lower in the patients with hypoproteinemia than in those with near-normal serum albumin concentrations (P<0.001). However, the mean (+/-SD) base-line serum free cortisol concentrations were similar in the two groups of patients (5.1+/-4.1 and 5.2+/-3.5 microg per deciliter [140.7+/-113.1 and 143.5+/-96.6 nmol per liter]) and were several times higher than the values in controls (0.6+/-0.3 microg per deciliter [16.6+/-8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated serum total cortisol concentrations were subnormal (18.5 microg per deciliter [510.4 nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia. In all 66 patients, including these 14 who had hypoproteinemia, the base-line and cosyntropin-stimulated serum free cortisol concentrations were high-normal or elevated. CONCLUSIONS: During critical illness, glucocorticoid secretion markedly increases, but the increase is not discernible when only the serum total cortisol concentration is measured. In this study, nearly 40 percent of critically ill patients with hypoproteinemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. Measuring serum free cortisol concentrations in critically ill patients with hypoproteinemia may help prevent the unnecessary use of glucocorticoid therapy.
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“Patients with diseases such as nephrotic syndrome (43) and liver disease (50) as well as those who are in the immediate postoperative period (51) or who require intensive care (52) may have lower CBG and albumin and hence, lower cortisol measurements.”
From Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline (2016) · cites this paper as [52]
In the citing paper
“By contrast, serum cortisol concentrations can be decreased in patients with low albumin and cortisol binding globulin, as in hypoalbuminemic states (such as advanced cirrhosis, nephrotic syndrome, and malnutrition), and prolonged critical illness (92, 93).”
From European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024) · cites this paper as [92]
In the citing paper
“For instance, activation and reserve capacity of the hypothalamic–pituitary–adrenal (HPA) axis in critically ill patients undergoing surgery was found to correlate better with serum free than total cortisol concentrations. The use of serum total cortisol alone could lead to a misdiagnosis of HPA axis insufficiency in up to 23% of these patients [241, 242].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [241]
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“Subsequent studies report a poor correlation between free and total cortisol levels, raising doubt as to the soundness of using total cortisol values.(97) Another problem is clinician skepticism that patients with high baseline cortisol values could benefit from even more glucocorticoid merely because they failed to r…”
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“hormone [8, 9], we carried out an additional investigation to determine the relationship between the serum levels of albumin and cortisol.”
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Clark, L., Preissig, C. M., Rigby, M. R., & Bowyer, F. P. (2008) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2008.03.001 · Cited by 19
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“chronic liver and renal disease), greatly affect TC levels (14-18).”
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“In critical illness, CBG concentrations decrease (16), and there is an increase in neutrophil elastase activity, both leading to increases in plasma-free cortisol (PFC).”
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Ten false beliefs about cortisol in critically ill patients
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“Free cortisol concentrations and the free cortisol index are elevated in response to acute stress despite low total cortisol concentrations and reduced concentrations of serum proteins, such as albumin and CBG [2,4].”
BackgroundPituitary-adrenal responses to human corticotropin-releasing hormone in critically ill patients
Dimopoulou, I., Alevizopoulou, P., Dafni, U. G., Orfanos, S. E., Livaditi, O., Tzanela, M., Kotanidou, A. N., Souvatzoglou, E., Kopterides, P., Mavrou, I., et al. (2006) · Intensive Care Medicine · doi:10.1007/s00134-006-0491-0 · Cited by 18
“However, there were no differences between the two groups in baseline CBG and albumin levels, which are the major blood transport protein for cortisol in humans [20].”
BackgroundRelative Adrenal Insufficiency in the ICU: Can We at Least Make the Diagnosis?
Meyer, N. J., & Hall, J. B. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200608-1168ed · Cited by 18
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“Serum free cortisol levels are elevated in patients with critical illness (1, 2).”
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“Free plasma cortisol determination is the most appropriate reflection of HPA axis activity, but unfortunately the methodology of serum free cortisol determination is laborious, time consuming, and expensive, making access to timely measurements for clinical guidance infeasible [5–7].”
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Low-dose steroid therapy does not affect hemodynamic response in septic shock patients
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Current Concepts in Resuscitation
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Secondary adrenal insufficiency in the acute phase of pediatric traumatic brain injury
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An endocrinologist's view on relative adrenocortical insufficiency in rheumatoid arthritis
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Vieira-Corrêa, M., Giorgi, R. B., de Oliveira, K. C., Hayashi, L. F., Costa‐Barbosa, F. A., & Kater, C. E. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01104-8 · Cited by 20
Diagnosis and treatment of ACTH deficiency
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“CBG levels also change substantially during critical illness and the reliability of total serum cortisol levels is likely to be reduced in this situation [38] compared to free cortisol levels [39].”
BackgroundHipotiroidismo autoimune refratário a altas doses de levotiroxina e hipocalcemia grave
Silva, C. M. D. S., & Souza, M. V. L. D. (2005) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302005000400020 · Cited by 16
“O hipotireoidismo descompensado poderia ser outro fator responsável pela não resposta ao teste com ACTH.”
InfluentialFlowers, K. C., & Shipman, K. E. (2023) · Diagnostics · doi:10.3390/diagnostics13081415 · Cited by 17
“, hypoalbuminemia and low CBG concentration, then a spuriously lower total cortisol concentration may be recorded [22].”
BackgroundKortikosteroidinsuffizienz bei kritisch Kranken
Briegel, J., Vogeser, M., Keh, D., & Marik, P. E. (2009) · Der Anaesthesist · doi:10.1007/s00101-009-1515-2 · Cited by 16
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“Relative” adRenal insufficiency in cRitical illness
Fleseriu, M., & Loriaux, D. L. (2009) · Endocrine Practice · doi:10.4158/ep09180.ra · Cited by 16
“An important insight into the use of free cortisol was provided by the work of Hamrahian et al (56) in 2004.”
Insuficiência adrenal relativa como preditora de gravidade de doença e mortalidade do choque séptico
Dallegrave, D. M., Silva, R. L., Becker, M., Gehrke, L. V., & Friedman, G. (2012) · Revista Brasileira de Terapia Intensiva · doi:10.1590/s0103-507x2012000400012 · Cited by 15
“Baseline cortisol (μg/dL) 19 [11-27] 24 [18-34] 0.”
BackgroundInfluentialKerlik, J., Penesová, A., Vlček, M., Imrich, R., Vogeser, M., & Rádiková, Ž. (2010) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2010.03.005 · Cited by 16
“Hence, measurement of total cortisol (TC) commonly used by clinicians for an interpretation of adrenal testing results may not accurately reflect biologically active cortisol levels in some clinical situations such as in critically ill patients [1].”
BackgroundSerum free cortisol as an ancillary tool in the interpretation of the low-dose 1-μg ACTH test
Limor, R., Tordjman, K. M., Marcus, Y., Greenman, Y., Osher, E., Sofer, Y., & Stern, N. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04080.x · Cited by 17
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“Second, similarly to previously published studies and according to the CIRCI definition, this study only measured total serum cortisol, which is influenced by hypoalbuminaemia, and not free cortisol which is the circulating form exerting a biological effect (25).”
ResultSalivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol.
Simunkova, K., Hampl, R., Hill, M., Doucha, J., Stárka, L., & Vondra, K. (2007) · Physiological Research · doi:10.33549/physiolres.930984 · Cited by 18
Infection, Immunity, and Hormones/Endocrine Interactions
Khardori, R. K., Adamski, A., & Khardori, N. M. (2007) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2007.06.002 · Cited by 16
Assessment of Adrenocortical Function in the Critically Ill
Rai, R., Cohen, J., & Venkatesh, B. (2004) · Critical Care and Resuscitation · doi:10.1016/s1441-2772(23)01857-4 · Cited by 16
Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage
LINDGREN, C., Dahlqvist, P. M., Lindvall, P., Nilsson, L. M., Koskinen, L., & Naredi, S. (2012) · Acta Anaesthesiologica Scandinavica · doi:10.1111/aas.12014 · Cited by 13
“This can result in falsely low mSC values.(5,21) In this study, the lowest CBG levels were found within the first 96 h after SAH0, indicating an early capillary leakage, of importance when evaluating mSC levels.”
BackgroundHormonal Therapy in Organ Donors
Opdam, H. I. (2019) · Critical Care Clinics · doi:10.1016/j.ccc.2018.11.013 · Cited by 14
Risk Factors and Outcome of Changes in Adrenal Response to ACTH in the Course of Critical Illness
de Jong, M. F. C., Beishuizen, A., van Schijndel, R. J. M. S., Girbes, A. R. J., & Groeneveld, A. B. J. (2011) · Journal of Intensive Care Medicine · doi:10.1177/0885066610393456 · Cited by 14
“010 Age, years 65 (33-78) 67 (18-92) 65 (18-92) 73 (37-84) Underlying disease Cardiovascular 14 (52) 15 (56) 21 (49) 8 (73) Renal 0 1 (4) 1 (2) 0 Pulmonary 2 (7) 1 (4) 3 (7) 0 Gastrointestinal 2 (7) 2 (7) 4 (9) 0 Neurological 1 (4) 1 (4) 2 (5) 0 Endocrinological 3 (11) 3 (11) 5 (12) 1 (9) Malignancy 2 (7) 2 (7) 2 (5)…”
den Berghe, G. V. (2021) · Journal of Anesthesia · doi:10.1007/s00540-021-02977-x · Cited by 15
Role of salivary cortisol determinations in the diagnosis of Cushing syndrome
Raff, H. (2004) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/01.med.0000132655.69704.8c · Cited by 14
Revisiting steroid treatment for septic shock: molecular actions and clinical effects - a review
Japiassú, A. M., Salluh, J. I., Bozza, P. T., Bozza, F. A., & Castro-Faria-Neto, H. C. (2009) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762009000400001 · Cited by 15
“…(below 10 mcg/dL) are indicative of adrenal failure; (v) serum levels of cortisol can be influenced by serum protein (particularly albumin) levels (Hamrahian et al. 2004); (vi) a positive response to steroid treatment generally corresponds to fast tapering of vasopressors (up to 3 days) and (vii)…”
BackgroundInfluentialEvaluation of adrenal function in critically ill children
Balbão, V. D. M. P., Costa, M. M. A., de Castro, M., & Carlotti, A. P. D. C. P. (2014) · Clinical Endocrinology · doi:10.1111/cen.12444 · Cited by 14
Common Endocrine Issues in the Pediatric Intensive Care Unit
Arnim, A. V. S. A.-V., Farris, R. W. D., Roberts, J. S., Yanay, O., Brogan, T. V., & Zimmerman, J. J. (2013) · Critical Care Clinics · doi:10.1016/j.ccc.2012.11.006 · Cited by 16
Evaluation of Endocrine Function
Guber, H. A., & Farag, A. F. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4377-0974-2.00024-5 · Cited by 15
Principles of Developmental Cardiovascular Physiology and Pathophysiology
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Endocrine aspects of critical illness
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Steroid use in PROWESS severe sepsis patients treated with drotrecogin alfa (activated)
Levy, H. A., Laterre, P., Bates, B. M., & Qualy, R. L. (2005) · Critical Care · doi:10.1186/cc3778 · Cited by 15
“It was recently reported that severe hypoproteinemia frequently results in concentrations of serum total cortisol in critically ill patients that are lower than expected, whereas free cortisol levels give a more accurate indication of response to corticotropin stimulation [25] and thus provide better identification of…”
BackgroundGeneralizable Molecular Switch Designs for In Vivo Continuous Biosensing
Saunders, J., Thompson, I. A. P., & Soh, H. T. (2025) · Accounts of Chemical Research · doi:10.1021/acs.accounts.4c00721 · Cited by 14
Adrenal insufficiency predicts early mortality in patients with cirrhosis
Chawlani, R., Arora, A., Ranjan, P., Sharma, P., Tyagi, P. K., Bansal, N. K., Singla, V., Arora, V., Kotecha, H., Kirnake, V., et al. (2014) · United European Gastroenterology Journal · doi:10.1177/2050640614552314 · Cited by 15
“We considered a normal response to SST to be a serum cortisol concentration of at least 18 lg/dl (497 nmol/l) at 60 minutes after the synacthen injection, as described in several studies.(11,12) Some authors suggest that tissue glucocorticoid activity rather than circulating glucocorticoid concentrations may be a pote…”
MethodGlucocorticoid Receptor Expression in Peripheral WBCs of Critically Ill Children*
Shibata, A. R. O., Troster, E. J., & Wong, H. R. (2015) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000000407 · Cited by 14
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Critical illness-related corticosteroid insufficiency in cancer patients
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“, 10, 15, 25, or 34 μg/dL) [11, 23], and assessment of serum free cortisol [24].”
BackgroundNicolas-Robin, A., Barouk, J., Darnal, E., Riou, B., & Langeron, O. (2011) · Anesthesiology · doi:10.1097/aln.0b013e31822a702f · Cited by 13
“misinterpretation of low serum total cortisol concentrations, thereby overestimating the incidence of AI.(8) In critically ill”
BackgroundMethodInfluentialEstablishing Normal Ranges of Basal and ACTH-Stimulated Serum Free Cortisol in Children
Eyal, O., Limor, R., Oren, A., Schachter-Davidov, A., Stern, N., & Weintrob, N. (2016) · Hormone Research in Paediatrics · doi:10.1159/000447946 · Cited by 12
Dissociation of ACTH and cortisol in septic and non-septic ICU patients
Raff, H., Biru, N., Reisinger, N., & Kramer, D. J. (2016) · Endocrine · doi:10.1007/s12020-016-1034-2 · Cited by 15
Adrenal exhaustion in septic patients with vasopressor dependency.
Guzman, J., & Guzman, C. B. (2007) · Journal of critical care · doi:10.1016/j.jcrc.2007.05.003 · Cited by 16
“Low cortisol concentrations have been found in patients with hypoproteinemia in spite of having normal or even high free cortisol concentrations [21].”
BackgroundChapter 1 – Etiology, Pathophysiology, and Phases of Neonatal Shock
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Relative adrenal insufficiency: an identifiable entity in nonseptic critically ill patients?
de Jong, M. F. C., Beishuizen, A., Spijkstra, J. J., Girbes, A. R. J., & Groeneveld, A. B. J. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02814.x · Cited by 13
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“Neonates and infants experience hypoproteinemia by virtue of their age as well as their critical illness, which could result in higher concentrations of unbound HC (16, 17, 24).”
Kosák, M., Hána, V., Hill, M., Šimůnková, K., Lacinová, Z., Kršek, M., & Marek, J. (2014) · Physiological Research · doi:10.33549/physiolres.932611 · Cited by 13
Elevated Baseline Cortisol Levels Are Predictive of Bad Outcomes in Critically Ill Children
Levy‐Shraga, Y., Pinhas‐Hamiel, O., Molina-Hazan, V., Tamir‐Hostovsky, L., Eini, Z. M., Lerner‐Geva, L., & Paret, G. (2016) · Pediatric Emergency Care · doi:10.1097/pec.0000000000000784 · Cited by 13
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Barlow, N., Holme, J., Stockley, R., & Clark, P. (2010) · Annals of Clinical Biochemistry · doi:10.1258/acb.2010.009246 · Cited by 15
Overview of the endocrine response to critical illness: How to measure it and when to treat
Hassan-Smith, Z. K., & Cooper, M. S. (2011) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2011.04.002 · Cited by 13
Cortisol concentrations and mortality from COVID-19
Choy, K. W. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30305-3 · Cited by 13
Primary adrenal insufficiency in adults: When to suspect, how to diagnose and manage
Lundholm, M. D., Ambalavanan, J., & Rao, P. P. R. (2024) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.91a.23072 · Cited by 15
“9,10 As a result, there are no recognized cortisol cutoff values for diagnosing adrenal insuffi ciency in this setting.”
Kyle, U. G., Jolliet, P., Genton, L., Meier, C. A., Mensi, N., Graf, J., Chevrolet, J.-C., & Pichard, C. (2005) · Intensive Care Medicine · doi:10.1007/s00134-005-2832-9 · Cited by 12
“... was based on the following clinical criteria: (a) body temperature 36� or below or 38�C or above; (b) heart rate 100/min or higher; (c) mean systemic arterial pressure 60 or lower or 120 mmHg or higher; (d) respiratory rate 20/min or less; (e) presence of infection, defined as a clear clinical source and/or positi…”
BackgroundMethodInfluentialWald, E. L., Backer, C., Dearani, J., Li, Z., Oliver, W. C., & Crow, S. S. (2017) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2016.11.030 · Cited by 10
Guerrero, J. (2017) · Revista médica de Chile (Impresa) · doi:10.4067/s0034-98872017000200011 · Cited by 6
Zannas, A. S., Kosyk, O., & Leung, C. S. (2020) · Genes · doi:10.3390/genes11121425 · Cited by 12
Serum albumin as a determinant of cortisol release in patients with acute ischemic stroke
Dziedzic, T., Pera, J., Wnuk, M. A., Szczudlik, A., & Słowik, A. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.12.017 · Cited by 12
Assessing adrenal function in cirrhotic patients: Is there a reliable test?
Thévenot, T., Borot, S., Rémy-Martin, A., Sapin, R., Penfornis, A., Martino, V. D., & Monnet, É. (2009) · Gastroentérologie Clinique et Biologique · doi:10.1016/j.gcb.2009.03.011 · Cited by 12
de Mello, R. C. V., Sad, E. F., Andrade, B. C., Neves, S. P. F., Santos, S. M. E., Sarquis, M., Marik, P. E., & Dias, E. P. (2011) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/s0004-27302011000700004 · Cited by 12
“This has been attributed to low transcortin levels in this population, since it has been shown that disproportionately larger increases in free, as compared with total cortisol, occur when the binding capacity of transcortin is exceeded (11-13).”
BackgroundKwon, Y. S., Suh, G. Y., Kang, E., Koh, W., Chung, M. P., Kim, H., & Kwon, O. J. (2007) · Journal of Korean Medical Science · doi:10.3346/jkms.2007.22.3.470 · Cited by 12
“Diagnosis of RAI is difficult because the expected cortisol levels vary with the type and severity of disease (5, 7) and with different serum levels of binding proteins (8).”
BackgroundAnnane, D., Pastores, S. M., Rochwerg, B. N., Arlt, W., Ra, B., Beishuizen, A., Briegel, J., Carcillo, J. A., Christ‐Crain, M., Cooper, M. S., et al. (2018) · Yearbook of pediatric endocrinology · doi:10.1530/ey.15.8.10 · Cited by 12
Defining normal adrenal function testing in the intensive care unit setting: A canine study*
Sweeney, D. A., Natanson, C., Banks, S. M., Solomon, S. B., & Behrend, E. N. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181cb0a25 · Cited by 12
“The interpretation of cortisol concentrations in critical illness has proven to be complex (2).”
BackgroundInfluentialOpioid-induced adrenal insufficiency: diagnostic and management considerations
Patel, E., & Ben-Shlomo, A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1280603 · Cited by 11
Bagate, F., Bedet, A., Tomberli, F., Boissier, F., Razazi, K., de Prost, N., Carteaux, G., & Dessap, A. M. (2021) · Annals of Intensive Care · doi:10.1186/s13613-021-00852-2 · Cited by 13
“Although we found no difference in protidemia level according to adrenal function, free cortisol is probably more suitable [35].”
BackgroundNaturalistic Stress Hormone Levels Drive Cumulative Epigenomic Changes along the Cellular Lifespan
Zannas, A. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168778 · Cited by 9
Guo, Z.-G., Pang, L.-W., Jia, X.-P., Wang, X., Su, X., Li, P., Mi, W., & Hao, J.-H. (2015) · Burns · doi:10.1016/j.burns.2014.04.021 · Cited by 13
“[17] Hamrahian AH, Oseni TS, Arafah BM.”
MethodSaliva stimulation with glycerine and citric acid does not affect salivary cortisol levels
Brorsson, C., Dahlqvist, P. M., Nilsson, L., & Naredi, S. (2014) · Clinical Endocrinology · doi:10.1111/cen.12423 · Cited by 11
Serum cortisol and inflammatory response in neutropenic fever
Juutilainen, A., Hämäläinen, S., Niemenpää, J., Kuittinen, T., Pulkki, K., Koivula, I., Niskanen, L., & Jantunen, E. (2011) · Annals of Hematology · doi:10.1007/s00277-011-1211-6 · Cited by 9
“In sepsis, the corticoidbinding globulin levels decrease resulting in an increase of free cortisol, and if a patient is severely hypoproteinemic, assessment of free cortisol is recommended for the diagnosis [26, 27 ].”
BackgroundComparison of total, salivary and calculated free cortisol levels in patients with severe sepsis
Elbüken, G., Karaca, Z., Tanrıverdi, F., Ünlühızarcı, K., Sungur, M., Doğanay, M., & Keleştimur, F. (2016) · Journal of Intensive Care · doi:10.1186/s40560-015-0125-0 · Cited by 10
“As a kind of critical illness, sepsis may lead to major changes in hypothalamo-pituitaryadrenal (HPA) axis that causes challenges in the evaluation of its functions in those patients [4, 5].”
BackgroundPrinciples of Developmental Cardiovascular Physiology and Pathophysiology
Noori, S., & Seri, I. (2019) · Hemodynamics and Cardiology · doi:10.1016/b978-0-323-53366-9.00001-6 · Cited by 8
Howell, G. M. S., & Tisherman, S. (2006) · Surgical Clinics of North America · doi:10.1016/j.suc.2006.08.001 · Cited by 8
Kwon, Y. S., Kang, E., Suh, G. Y., Koh, W., Chung, M. P., Kim, H., Kwon, O. J., & Chung, J. H. (2009) · Journal of Korean Medical Science · doi:10.3346/jkms.2009.24.4.668 · Cited by 11
“However, the diagnosis of RAI in critically-ill patients is difficult because the expected cortisol levels vary with the type and severity of disease (4, 10), as well as with different serum levels of binding proteins (11).”
BackgroundBarthel, A., Willenberg, H. S., Grüber, M., & Bornstein, S. R. (2015) · Elsevier eBooks · doi:10.1016/b978-0-323-18907-1.00102-5 · Cited by 11
Li, C., Hu, J., Hu, N., Zhao, J., Li, Q., Han, Y., Liu, Y., Hu, X., Zheng, L., & Cao, Q. (2024) · Analytical Methods · doi:10.1039/d4ay00401a · Cited by 10
Al‐Hakeim, H. K., Al-Khakani, M. F., & Al-Kindi, M. A. (2015) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/38158 · Cited by 10
“However, the possibility of chronic liver disease occurring because of iron overload may reduce the synthesis of hepatic cortisol-binding globulin, which can result in abnormally low serum cortisol [25].”
BackgroundNayil, K., Ramzan, A., Shoaib, Y., Bashir, M. I., Wani, A. A., & Shafiq, A. (2013) · Intern J Endocrinol Metab · doi:10.5812/ijem.8241 · Cited by 10
“Studies which have reported these changes have been carried out mostly in polytrauma, septic shock and renal failure (1-3, 10, 11, 14-20).”
BackgroundPerioperative Management of Shock in Two Fontan Patients With Plastic Bronchitis
Singhal, N. R., da Cruz, E. M., Nicolarsen, J. R., Schwartz, L. I., Merritt, G., Barrett, C., Twite, M. D., & Ing, R. J. (2013) · Seminars in Cardiothoracic and Vascular Anesthesia · doi:10.1177/1089253213475879 · Cited by 10
“7 μg/dL), which was lower than would have been expected with the stress response from the intervention.(23) Patient 2 was receiving steroids at the time of admission to the CICU, and both patients required treatment with stress-dose hydrocortisone.”
BackgroundEndocrine Markers of Severity and Prognosis in Critical Illness
Nylen, E. S., Seam, N., & Khosla, R. (2006) · Critical Care Clinics · doi:10.1016/j.ccc.2005.08.002 · Cited by 10
“Many patients with frequent hypoproteinemia have demonstrated a robust cortisol response when assessed by serum-free cortisol assays, which more accurately reflect bioactive cortisol [3].”
BackgroundBrossaud, J., Gatta, B., Tabarin, A., & Corcuff, J. (2015) · Clinical Chemistry and Laboratory Medicine · doi:10.1515/cclm-2014-0912 · Cited by 11
Bergt, S., Wagner, N., Heidrich, M., Butschkau, A., Nöldge-Schomburg, G. E. F., Vollmar, B., & Roesner, J. P. (2013) · Shock · doi:10.1097/shk.0000000000000029 · Cited by 10
“creased levels of endogenous cortisol production from a relative shift in unbound hormone (21).”
Background
Metadata
- Authors
- Hamrahian, A. H., Oseni, T. S., & Arafah, B. M.
- Affiliations
- University Hospitals of Cleveland (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-04-15
- Volume
- 350
- Issue
- 16
- Pages
- 1629-1638
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2125017989
- Cited by
- 726
- References
- 40
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 17 · 2021: 18 · 2020: 17 · 2019: 22 · 2018: 14 · 2017: 28 · 2016: 28 · 2015: 37 · 2014: 41 · 2013: 26 · 2012: 34
- FWCI
- 40.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01RR000080)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Health Professions › Medical Laboratory Technology › Clinical Laboratory Practices and Quality Control
- Keywords
- free cortisol, cortisol-binding protein, hypoproteinemia, critically ill patients, ACTH stimulation test, glucocorticoid secretion, adrenal function, serum albumin, hypercortisolism, adrenal insufficiency, aldosterone, critically ill children, critically ill adults, critically ill neonates, critically ill infants
- MeSH terms
- Adrenal Insufficiency, Adrenocorticotropic Hormone, Aged, Aldosterone, Cosyntropin, Humans, Hydrocortisone, Hypoproteinemia, Middle Aged, Pituitary-Adrenal System, Regression Analysis, Critical Illness, APACHE, Hypoalbuminemia
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