Serum Total Cortisol Concentrations Research Articles

Circulating Hypothalamic-Pituitary-Adrenal Axis Hormones and Insulin Concentrations in Horses and Ponies

Mechanisms resulting in breed predispositions to insulin dysregulation (ID) are poorly characterized. Cortisol antagonizes insulin, and free, biologically active cortisol can be increased in ID. Breed-related differences in serum free cortisol fraction (FCF) could contribute to ID, but FCF has not been quantified in equidae predisposed to ID, such as ponies. To compare FCF and other hypothalamic-pituitary-adrenal (HPA) axis hormones between horses and ponies during health and ID. We hypothesized: (1) FCF is higher in ponies than horses in health, and is higher still in ponies with ID and obesity; and (2) FCF is positively correlated with insulin in horses and ponies during health and ID. Thirty-three horses and 24 ponies were sampled before morning feeding in their normal routine. Plasma ACTH and insulin and serum total cortisol concentrations and FCF were measured. ID was defined as evidence of hyperinsulinemia at rest or after oral sugar administration. Data were compared with Mann-Whitney tests and Spearman correlation analysis (P < 0.05). Total cortisol, free cortisol, insulin concentrations, and FCF were comparable in healthy horses (n = 24) and ponies (n = 12), but ACTH concentrations were 29% higher in ponies than in horses (P = 0.016). In animals with ID, total cortisol, free cortisol, and insulin concentrations were similar between horses and ponies, but FCF was increased 40% in ponies (n = 12) compared to horses (n = 9). These data demonstrate differences in insulin, ACTH, and free cortisol during health and ID between ponies and horses.

Assessment of early morning serum cortisol levels in adult male patients with alcohol-related disorders

BackgroundAlcohol-related disorders are a major health problem among Indian male professionals because of the unique nature of socioeconomic and demographic conditions. Various studies have highlighted the association between alcohol-related disorders and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, but the evidence accrued so far is inconclusive. In our study, we have assessed early morning serum total cortisol concentration among Indian adult male population affected with alcohol-related disorder. MethodsA case-based cross-sectional study in which all consecutive patients admitted in the psychiatry ward of a tertiary care hospital with diagnosis of ‘alcohol-related disorders’, who were meeting all the inclusion criteria, and who had none of the exclusion criteria were part of the study. Diseased controls and healthy controls were chosen by applying strict inclusion and exclusion criteria. Serum early morning (0400 h) total cortisol levels were estimated using automated quantitative enzyme-linked fluorescent assay technique. Results98 psychiatric patients and 50 healthy controls were evaluated. Out of these 98 patients 66 patients were diagnosed cases of alcohol-related disorder. Morning serum total cortisol levels in patients with alcohol-related disorders was found to be significantly different from healthy controls. ConclusionOur study suggests that alcohol-related disorders are associated with chronic changes in HPA axis and significant alteration of early morning serum total cortisol levels were demonstrated in this group of patients.

Glucocorticoid metabolism in critically ill dogs (Canis lupus familiaris)

Critical illness due to sepsis is a major global health concern associated with a high burden of mortality and cost. Glucocorticoid dysregulation in human sepsis is associated with poorer outcomes. This study examines glucocorticoid metabolism in septic canine patients to delineate elements of cellular dysregulation in common with critically ill humans and explore potential differences. This was a prospective case–control study conducted in the veterinary specialist critical care departments of two University teaching hospitals. Critically ill canine patients with naturally occurring sepsis or septic shock were compared with an in-hospital control population. Serum total, bound, and free cortisol concentrations were increased in septic shock (P < 0.001), and higher bound cortisol was associated with nonsurvival (P = 0.026). Urinary Gas Chromatography-Tandem Mass Spectrometry was performed to assess urinary glucocorticoid metabolites and estimate intracellular glucocorticoid metabolism. Decreased renal 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity inferred from increased urinary cortisol-to-cortisone ratio was observed in critically ill dogs (P < 0.001). Decreased 11βHSD2 activity (P = 0.019) and increased A-ring reduction of cortisone (P = 0.001) were associated with nonsurvival within the critically ill dogs. Intriguingly, two dogs were identified with low circulating total cortisol (<2 mg/dL) associated with increased A-ring reduction of cortisol, not previously described. Investigation of spontaneous canine sepsis and septic shock reveals dysregulation of cortisol to cortisone conversion similar to that observed in human patients, but with differences in A-ring reduction compared with those reported in humans. In addition, two dogs with high levels of cortisol inactivation associated with low circulating cortisol concentrations were identified.

SAT-220 Oral Contraceptives and Their Effect on the Evaluation of Cushing's Syndrome: A Case Report

Background In the evaluation of Cushing’s syndrome (CS), oral contraceptives may lead to false-positive results by raising the serum levels of cortisol-binding globulin (CBG). Clinical Case An 18-year old Chinese lady presented with weight gain, irregular menses and hirsutism. History was unremarkable for hypothyroidism, hyperprolactinemia, eating disorders, and exogenous steroid use. On examination, she was overweight (body mass index (BMI) 26.9 kg/m2) with rounded facies, hirsutism and dorsal cervical fat pad. Initial biochemical tests showed high cortisol and ACTH levels: ACTH 66.6 pmol/L (RI 0-10.2 pmol/L) and random cortisol 958 nmol/L (RI: 240-618 nmol/L). She was referred to our department for evaluation of possible Cushing’s syndrome. Further history revealed that the patient was on a combined estrogen-progestin oral contraceptive pill (OCP). Confirmatory tests after cessation of the OCP for 6 weeks revealed normal 24-hr urinary cortisol levels (231 and 255 nmol/day, RI: 59-413 nmol/day) and a normal 1 mg dexamethasone suppression test (44 nmol/L after administration of 1 mg dexamethasone overnight, RI <50nmol/L). A progesterone challenge test induced withdrawal bleeding, consistent with an estrogen-sufficient anovulatory state such as that seen in Polycystic Ovarian Syndrome. Regular menstrual cycles returned after deliberate weight loss to a BMI of 26.0 kg/m2). Discussion and Conclusion OCPs increase total cortisol concentrations by increasing circulating CBG without affecting the unbound fraction (1). Women on OCPs may hence display elevated serum total cortisol concentrations without increased cortisol activity. These elevations are dependent on estrogen dose, and usually not seen with progestogen-only or low-dose estrogen (0.05 mg mestranol or less) preparations (2). Other drugs interfering with cortisol clearance, such as CYP3A4 inhibitors and inducers, may also influence test results (3). Current guidelines suggest that estrogen-containing drugs should be discontinued for at least 6 weeks so as to prevent false-positive results, which can potentially lead to unnecessary procedures or surgery. A thorough drug history is therefore crucial in the evaluation of CS. References (1) Qureshi AC, Bahri A, Breen LA, et al. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol (Oxf). 2007; 66: 632-5 (2) C. W. Burke. The effect of oral contraceptives on cortisol metabolism. J Clin Pathol Suppl (Assoc Clin Pathol). 1969; 3: 11-18. (3) M. Vastbinder, M. Kuindersma et al. The influence of oral contraceptives on overnight 1 mg dexamethasone suppression test. Neth J Med. 2016 May;74(4): 158-61.

Critical illness?related corticosteroid insufficiency in children: A single center, prospective, cohort study

Background: Although guidelines for diagnosis and management of critical illness?related corticosteroid insufficiency (CIRCI) in adults are developed, there is a paucity of data on CIRCI in children. Objective: To study the incidence, risk factors, mechanism, and associations of CIRCI in children using adrenocorticotropic hormone (ACTH) stimulation test. Materials and Methods: Single?center prospective cohort study was conducted in eight bedded pediatric intensive care unit of teaching hospital over a period of 1 year. Serum total cortisol concentration was measured in 110 critically ill children before and after stimulation with 250 ?g ACTH. CIRCI was defined by post?ACTH increment in serum cortisol ?9 ?g/dl. Children with and without CIRCI were compared. Results: Incidence of CIRCI was 38.2%. Children with CIRCI had higher median age (34 vs. 18 months), higher pediatric risk of mortality score (17.79±2.60 vs. 16.37±3.68), and significantly higher basal cortisol levels (27.37±11.64 vs. 22.02±7.26) (p=0.004) than those without CIRCI. There was a significantly higher (p=0.000) requirement of catecholamines (2.71±0.457 vs. 2.00±0.792) and higher additional fluid boluses (15.79±4.7 vs. 10.65±4.60) in children with CIRCI. However, duration of catecholamine use was not significantly different between two groups. The presence of CIRCI was not found to be an independent risk factor for mortality. For each additional use of catecholamine, the risk of CIRCI increased to 5.6 times; and for each extra fluid bolus, the risk increased to 1.2 times. Conclusion: CIRCI occurs in a wide spectrum of diseases in critically ill children associated with increased need for catecholamine and fluids. CIRCI is likely to be multifactorial in etiology and associated with high basal cortisol levels.

Assessment of adrenal function in patients with acute hepatitis using serum free and total cortisol

BackgroundAdrenal dysfunction is frequently reported in severe acute hepatitis using serum total cortisol. AimsBecause 90% of serum cortisol is bound to proteins that are altered during stress, we investigated the effect of decreased cortisol-binding proteins on serum total and free cortisol in severe acute hepatitis. Methods43 severe and 31 non-severe acute hepatitis and 29 healthy controls were enrolled consecutively and studied prospectively. Baseline (T0) and cosyntropin-stimulated (T60) serum total and free cortisol concentrations were measured. ResultsT0 and T60 serum total cortisol did not differ significantly between severe, non-severe hepatitis and healthy controls. Conversely, serum free cortisol (T0p=0.012; T60p<0.001) concentrations increased from healthy controls to severe hepatitis, accompanied by a decrease in corticosteroid-binding globulin and albumin (all p<0.001). In acute hepatitis (n=74), patients with “low” corticosteroid-binding globulin (<28mg/L) had higher T0 serum free cortisol than others (103.1 [61.2–157] vs. 56.6 [43.6–81.9]nmol/L, p=0.0024). Analysis of covariance showed that at equal concentration of total cortisol, the free cortisol concentration was significantly higher in severe than in non-severe hepatitis (p<0.001) or healthy controls (p<0.001). ConclusionsIn severe hepatitis, the decrease in cortisol-binding proteins impairs correct diagnosis of adrenal dysfunction. This could be corrected by measuring or estimating free cortisol.

Serum cortisol concentrations in horses with colic

Few studies have evaluated cortisol concentrations in horses with colic. In humans with septic shock, high cortisol levels are associated with an increased risk of death. The objectives of this study were to compare the serum total cortisol concentrations (STCCs) in horses with colic to those without colic, and to assess whether the STCC relates to the pathological nature or outcome of the disease.STCCs were determined at presentation in horses with colic and in systemically healthy ‘control’ horses. Horses with colic were grouped based on clinical and clinico-pathological parameters at admission, treatment, lesion type and location, and outcome. Univariable and multivariable logistic regression were performed using two different outcome measures: (a) whether the horse had colic or not (yes vs. no), and (b) horse STCC (≥200 nmol/L vs. <200 nmol/L).Horses were more likely to have colic if they presented with high STCCs (≥200 nmol/L compared with <200 nmol/L). Horses with colic and with STCCs ≥200nmol/L were more likely to have moderate or severe colic signs (compared with mild colic) and heart rates >45 beats per min (compared with ≤45 beats per min). It was concluded that colic in horses is associated with elevated STCCs, and increased STCC in horses with colic appears to relate to the severity of the disease. STCCs may provide additional decision-making and prognostic information in horses with colic but further studies are required to avoid misinterpretations associated with the wide variation in STCCs.

Detection of endogenous cortisol in equine tears and blood at rest and after simulated stress

To determine whether cortisol is present in equine tears at rest and during simulated stress and compare tear cortisol to serum free and total cortisol. Fourteen healthy adult horses were included. Paired tear total cortisol and serum total and free cortisol concentrations were measured with ELISA, chemiluminescent immunoassay, and ultrafiltration methodology, respectively, in 10 horses at rest once daily for five consecutive days. In an additional four horses, paired tear and serum samples were collected for cortisol measurement before and after adrenocorticotropic hormone (ACTH) stimulation (cosyntropin, 1 μg/kg IV). Cortisol was detectable in equine tears at rest. Following ACTH stimulation, tear cortisol increased significantly from baseline at 60-120 min (P ≤ 0.001). Serum total and free cortisol also increased significantly at 30-180 min after ACTH stimulation (P ≤ 0.001). Both serum and tear cortisol returned to baseline concentrations by 360 min. Changes in tear cortisol were similarly associated with changes in serum total and free cortisol, although high tear cortisol concentrations suggest a portion of tear cortisol may be protein-bound. Cortisol is present in equine tears and increases in concert with serum cortisol following ACTH stimulation. Further study is needed to determine whether endogenous cortisol in tears contributes to ocular pathology.

Pre-Operative and Early Post-Operative Factors Associated with Surgical Site Infection after Laparoscopic Sleeve Gastrectomy

Surgical procedures on obese patients are expected to have a high incidence of surgical site infection (SSI). The identification of pre-operative or early post-operative risk factors for SSI may help the surgeon to identify subjects in risk and adequately optimize their status. We conducted a study of the association of comorbidities and pre- and post-operative analytical variables with SSI following laparoscopic sleeve gastrectomy for the treatment of morbid obesity. We performed a prospective study of all morbidly obese patients undergoing laparoscopic sleeve gastrectomy as a bariatric procedure between 2007 and 2011. An association of clinical and analytical variables with SSI was investigated. The study included 40 patients with a mean pre-operative body mass index (BMI) of 51.2±7.9 kg/m(2). Surgical site infections appeared in three patients (7.5%), of whom two had an intra-abdominal abscess located in the left hypochondrium and the third had a superficial incisional SSI. Pre-operatively, a BMI >45 kg/m(2) (OR 8.7; p=0.008), restrictive disorders identified by pulmonary function tests (OR 10.0; p=0.012), a serum total protein concentration <5.3 g/dL (OR 13; p=0.003), a plasma cortisol >30 mcg/dL (OR 13.0; p=0.003), and a mean corpuscular volume (MCV) <82 fL (OR 1.6; p=0.04) were associated with post-operative SSI. Post-operatively, a serum glucose >128 mg/dL (OR 4.7; p=0.012) and hemoglobin <11g/dL (OR 7.5; p=0.002) were associated with SSI. The study supports the role of restrictive lung disorders and the values specified above for preoperative BMI, serum total protein and cortisol concentrations, and MCV, and of post-operative anemia and hyperglycemia as risk factors for SSI. In these situations, the surgeon must be aware of and seek to control these risk factors.

English

&nbsp; This&nbsp;study&nbsp;was conducted to&nbsp;evaluate&nbsp;the effect of supplemental chromium on performance and blood serum biochemistry of dairy cows. Thus,&nbsp;20&nbsp;multiparous Holstein cows (parity 3) were equally divided into two groups, group one (control), which received no chromium supplementation and group two (treatment) which received 5 g/day chromium methionine from week 5 prior to parturition until 12 weeks thereafter. Milk production and milk composition were evaluated on 4, 8 and 12 weeks after parturition. Serum biochemistry concentrations (serum glucose, cholesterol, triglyceride, total protein, and cortisol and insulin concentration) and blood hematology (red blood cell, hematocrit, hemoglobin concentration and percentage neutrophils, lymphocytes, monocytes, basophiles, eosinophils and ratio of neutrophils to lymphocytes) were measured on 2 and 5 weeks prior to parturition and 1 and 4 weeks thereafter. Results indicate that milk production was significantly affected by chromium-methionine supplementation during the entire period (P&lt;0.01) but no significant effect on milk composition was found. Supplemental chromium had no significant effect on serum glucose, cholesterol, triglycerides and insulin concentration and blood hematology parameters (P&lt;0.05). However, chromium supplementation tended to increase significantly, serum total protein concentration and decrease cortisol concentration (P&lt;0.05). The results of this experiment showed that chromium methionine supplementation in multiparous dairy cows diet may improve their milk yield in transition period. &nbsp; Key words:&nbsp;Dairy cow, transition period, chromium-methionine, milk yield, serum biochemistry.

Free Cortisol and Accuracy of Total Cortisol Measurements in the Diagnosis of Adrenal Insufficiency in Brain-dead Patients

After brain death, adrenal insufficiency (AI) is very common and may be one of the mechanisms that contributes to hemodynamic instability and loss of potential organ donors. However, when diagnosed by total cortisol measurement, critically ill patients may be overdiagnosed as having AI. The aims of this study were to assess the prevalence of AI when diagnosed using free cortisol measurement and the accuracy of total cortisol measurement to diagnose AI in brain-dead patients. All consecutive brain-dead patients were included in this single-center noninterventional clinical observation study. Assessment of adrenocorticotropin, corticosteroid-binding globulin, baseline and tetracosactin-stimulated serum free and total cortisol concentrations were performed. AI was defined as a baseline free cortisol concentration ≤ 55 nM(-1) and/or Δ free cortisol ≤ 55 nM(-1). Patients were considered to have a low albumin concentration if less than 25 g · L(-1) and a low corticosteroid-binding globulin concentration if less than 27 mg · L(-1) in men or 31 mg · L(-1) in women. Among the 42 included patients, the incidence of AI was 83% (95% CI, 69-93%). Baseline total cortisol was correlated with baseline free cortisol, whatever the albumin or corticosteroid-binding globulin concentration. The area under the receiver operating characteristic curve of baseline total cortisol measurement to diagnose AI was 0.94 (95% CI, 0.81-0.98). The optimal cutoff was 485 nM(-1), providing a sensitivity and a specificity of 89% and 100%, respectively. Total baseline cortisol measurement is accurate and sufficient to diagnose AI in brain-dead patients, even if albumin or corticosteroid-binding globulin concentrations are low.

Serum Free Cortisol Fraction in Healthy and Septic Neonatal Foals

Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals. In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration. Fifty-one septic foals; 11 healthy foals; 6 healthy horses. In this prospective clinical study, foals meeting criteria for sepsis at admission were enrolled. University-owned animals served as healthy controls. Basal and cosyntropin-stimulated total cortisol concentration and percent free cortisol (% free cortisol) were determined by chemiluminescent immunoassay and ultrafiltration/ligand-binding methods, respectively. Group data were compared by ANOVA, Mann-Whitney U-tests, and receiver operator characteristic curves. Significance was set at P < .05. Basal % free cortisol was highest in healthy foals at birth (58 ± 8% mean ± SD), and was higher (P ≤ .004) in healthy foals of all ages (33 ± 6 to 58 ± 8%) than in adult horses (7 ± 3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P ≤ .03) in foals with shock (total = 6.2 ± 8.1 μg/dL; free = 3.5 ± 4.8 μg/dL versus total = 10.8 ± 6.0 μg/dL; free = 6.9 ± 3.3 μg/dL in foals without shock) and in nonsurvivors (total = 3.8 ± 6.9 μg/dL; free = 1.9 ± 3.9 μg/dL versus total = 9.1 ± 7.7 μg/dL; free = 5.5 ± 4.4 μg/dL in survivors). Free cortisol was no better than total cortisol at predicting disease severity or outcome in septic foals. Serum free cortisol is impacted by age and illness in the horse. There is no advantage to measuring free over total cortisol in septic foals.

Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol

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. 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). 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. 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.

Neuromuscular and Hormonal Responses to Constant and Variable Resistance Loadings

The purpose of this study was to investigate the acute effects of constant and variable resistance exercise on neuromuscular and endocrine responses during maximal strength and hypertrophic loadings. Thirteen young men (age = 28.4 ± 3.7 yr) took part in four loadings (maximal strength and hypertrophic loadings using both constant and variable resistance) in a counterbalanced order. Maximal strength loadings consisted of 15 sets of one repetition at 100% one-repetition maximum, and hypertrophic loadings consisted of five sets of 10 repetitions (initial load of 80% one-repetition maximum). Preloading, immediately postloading, 15 min postloading, and 30 min postloading tests consisted of maximal bilateral isometric leg press, venous blood samples (analyzed for total testosterone, growth hormone, and cortisol), and fingertip blood lactate samples. Concentric force and vastus lateralis, vastus medialis, rectus femoris, and biceps femoris EMG was recorded throughout each loading protocol and analyzed over 20° segments. Force and quadriceps EMG was greater from 120° to 180° knee angle (P < 0.05) during variable resistance hypertrophic loadings. Larger increases in concentric quadriceps muscle activation and slower recovery in isometric force and muscle activation were observed during variable resistance hypertrophic loadings. Preloading to postloading serum total testosterone, growth hormone, and cortisol concentration increased during variable resistance hypertrophic loading, whereas during constant resistance loadings, only growth hormone increased (P = 0.051). During 30 min postloading, growth hormone and cortisol concentrations remained elevated after both hypertrophic loadings. A greater level of neuromuscular fatigue and larger responses in serum hormone concentrations occurred after hypertrophic variable resistance loading. These findings indicate greater fatigability during variable resistance loading and that this fatigability influences acute hormonal responses.

Grizzly bear corticosteroid binding globulin: Cloning and serum protein expression

Serum corticosteroid levels are routinely measured as markers of stress in wild animals. However, corticosteroid levels rise rapidly in response to the acute stress of capture and restraint for sampling, limiting its use as an indicator of chronic stress. We hypothesized that serum corticosteroid binding globulin (CBG), the primary transport protein for corticosteroids in circulation, may be a better marker of the stress status prior to capture in grizzly bears ( Ursus arctos). To test this, a full-length CBG cDNA was cloned and sequenced from grizzly bear testis and polyclonal antibodies were generated for detection of this protein in bear sera. The deduced nucleotide and protein sequences were 1218 bp and 405 amino acids, respectively. Multiple sequence alignments showed that grizzly bear CBG (gbCBG) was 90% and 83% identical to the dog CBG nucleotide and amino acid sequences, respectively. The affinity purified rabbit gbCBG antiserum detected grizzly bear but not human CBG. There were no sex differences in serum total cortisol concentration, while CBG expression was significantly higher in adult females compared to males. Serum cortisol levels were significantly higher in bears captured by leg-hold snare compared to those captured by remote drug delivery from helicopter. However, serum CBG expression between these two groups did not differ significantly. Overall, serum CBG levels may be a better marker of chronic stress, especially because this protein is not modulated by the stress of capture and restraint in grizzly bears.

Free Cortisol in Sepsis and Septic Shock

Severe sepsis activates the hypothalamopituitary axis, increasing cortisol production. In some studies, hydrocortisone substitution based on an adrenocorticotropic hormone-stimulation test or baseline cortisol measurement has improved outcome. Because only the free fraction of cortisol is active, measurement of free cortisol may be more important than total cortisol in critically ill patients. We measured total and free cortisol in patients with severe sepsis and related the concentrations to outcome. In a prospective study, severe sepsis was defined according the American College of Chest Physicians/Society of Critical Care Medicine criteria. Blood samples were drawn within 24 h of study entry. Serum cortisol was analyzed by electrochemiluminescence immunoassay. The Coolens method was used for calculating serum free cortisol concentrations. Blood samples were collected from 125 patients, of whom 62 had severe sepsis and 63 septic shock. Hospital mortality was 21%. Calculated free serum cortisol correlated well with serum total cortisol (r = 0.90, P < 0.001). There was no difference in the total cortisol concentrations in patients with sepsis and septic shock (728 +/- 386 nmol/L vs 793 +/- 439 nmol/L, P = 0.44). Nonsurvivors had higher calculated serum free (209 +/- 151 nmol/L) and total (980 +/- 458 nmol/L) cortisol concentrations than survivors (119 +/- 111 nmol/L, P = 0.002, and 704 +/- 383 nmol/L, P = 0.002). Depending on the definition, the incidence of adrenal insufficiency varied from 8% to 54%. Clinically, calculation of free cortisol does not provide essential information for identification of patients who would benefit from corticoid treatment in severe sepsis and septic shock.

Pituitary-adrenal function in patients with acute subarachnoid haemorrhage: a prospective cohort study

IntroductionSubarachnoid haemorrhage (SAH) may damage the hypothalamo-pituitary-adrenal gland (HPA) axis and disturb cortisol metabolism. There are no available data that relates to the response of the HPA axis in the acute phase of SAH. We aimed to characterise the behavior of serum adrenocorticotropic hormone (ACTH), total cortisol, stimulated total cortisol and free cortisol concentrations in acute aneurysmal SAH.MethodsA prospective cohort study was conducted of patients with acute aneurysmal SAH (n = 30) admitted to a tertiary university hospital. Patients admitted for elective aneurysmal surgery (n = 16) served as the control group. An ACTH stimulation test was performed twice during the first week and at three months. The main outcome measure was description of the ACTH-cortisol response by calculating serum free cortisol and measuring total cortisol and ACTH concentrations. A mixed models method was used for testing between the groups, allowing heterogeneity between the groups.ResultsPatients with SAH had higher initial serum total cortisol (mean +/- SD; 793 +/- 312 nmol/L) and free cortisol concentrations (83 +/- 55 nmol/L) than control patients (535 +/- 193 nmol/L, p = 0.001 and 33 +/- 18 nmol/L, p < 0.001, respectively). Thereafter, there were no differences in this respect. Serum free and total cortisol concentrations correlated but were unaffected by the severity of SAH. ACTH concentrations were comparable between SAH and control groups. Patients with Hunt-Hess grades IV to V had higher ACTH concentrations at day one (10.7 +/- 7.1 pmol/l/L) and day five (8.2 +/- 7.7 pmol/L) than patients with grade I-III (day one: 3.8 +/- 2.0 pmol/L, p = 0.002; day five: 4.7 +/- 1.8 pmol/L, p = 0.04).ConclusionsCalculation of serum free cortisol concentration was not helpful in identifying patients with potential hypocortisolism. SAH severity did not affect cortisol concentrations, possibly indicating relative pituitary-adrenal insufficiency in patients with more severe bleeding.Trial registrationClinicalTrials.gov Identifier NCT00614887.

Is free plasmatic cortisol measurement useful in intensive care unit

Serum cortisol free fraction is responsible for its physiological function. Determination of serum total cortisol concentration does not allow accurate evaluation of hypothalamic pituitary adrenal axis when there is a quantitative variation in serum transcortin. Although free cortisol can be assayed by salivary or urinary cortisol measurements, these methods can not be easily applied in intensive care units. Free plasmatic cortisol measurement could provide a better reflect of circulating cortisol in patients with critical illness whom have a decreased concentration of binding proteins and whom adrenal status is an important prognostic factor. Free cortisol can be measured after separation from bound cortisol, calculated with equation based on equilibrium binding or evaluated by cortisol/CBG ratio. In various studies, free plasmatic cortisol allows in critical care patients a better appreciation of adrenal status than total cortisol and be more differential than total cortisol increment after stimulation with synacthen used to diagnose "relative adrenal insufficiency".

Measurements of Serum Free Cortisol in Critically Ill Patients

Patients and Measurements: Baseline serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients with an APACHE score of 15 or higher, 33 healthy volunteers, and 7 patients with adrenal insufficiency secondary to hypopituitarism. Patients were further divided into two groups based on their serum albumin concentrations of ≤ 2.5 g/dL (low albumin group, n=36) or >2.5 g/dL (normal albumin group, n=30).

Measurements of serum free cortisol in critically ill patients.

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. 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). 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. 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.