title: Comparison of total, salivary and calculated free cortisol levels in patients with severe sepsis.
abstract: BACKGROUND
  The purposes of the study were to compare serum total cortisol (STC), salivary cortisol (SaC) and calculated free cortisol (cFC) levels at baseline and after the adrenocorticotrophic hormone (ACTH) stimulation test in patients with severe sepsis (SS) and determine the suitability of use of SaC and cFC levels instead of STC for the diagnosis of adrenal insufficiency (AI) in patients with SS. And secondary aims of this study were to compare these parameters in patients with SS with healthy controls and check their effects on survival status of the patients.
  
  
  METHODS
  Thirty patients with SS (15 men and 15 women) were compared with 16 healthy controls. Low-dose (1 μg) ACTH stimulation test was performed to the patients on the first, seventh and 28th days of diagnosis of SS, but in control group, 1 μg ACTH stimulation test was performed only once. STC, SaC and cFC levels were measured during ACTH stimulation test.
  
  
  RESULTS
  Patients were categorized as having low or high baseline STC according to a cut-off level of 10 μg/dL. In high STC group, baseline and peak SaC levels were found to be 2.3 (0.2-9.0) and 3.4 (0.5-17.8) μg/dL on D1 and 1.1 (0.8-4.6) and 2.6 (1.3-2.9) μg/dL on D7, respectively. In the control group, baseline and peak SaC levels were 0.4 (0.1-1.4) and 1.1 (0.4-2.5) μg/dL, respectively. Baseline and peak SaC levels after ACTH stimulation were found to be higher in high STC group than in controls, but they were found to be similar in low STC and control groups. In high STC group, cFC levels were 0.3 (0.1-0.3) and 0.4 (0.3-0.7) μg/dL on D1 and 0.2 (0.1-0.3) and 0.4 (0.1-0.7) μg/dL on D7, respectively. In the control group, baseline and peak cFC levels were 1.7 (0.4-1.9) and 1.8 (1.0-6.6) μg/dL, respectively. cFC levels were found to be lower in patients with SS subgroups than in the control group. Baseline and stimulated STC, SaC and cFC levels did not differ according to the survival status. SaC, cFC and STC levels were found to be correlated with each other.
  
  
  CONCLUSIONS
  SS is associated with increased SaC, but decreased cFC levels when baseline STC is assumed to be sufficient. When STC level is assumed to be insufficient, SaC levels remain unchanged, but cFC levels are decreased. Lower STC levels is not associated with increased mortality in patients with SS. More data are needed in order to suggest the use of SaC and cFC instead of STC.
  
  
  BACKGROUND
  ClinicalTrials.gov No: NCT02589431.
authors.affiliation: Department of Endocrinology and Metabolism, Erciyes University Medical School, 38039 Kayseri, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Elbuken
authors.affiliation: Department of Endocrinology and Metabolism, Erciyes University Medical School, 38039 Kayseri, Turkey.
authors.forename: Zuleyha
authors.initials: Z
authors.lastname: Karaca
authors.affiliation: Department of Endocrinology and Metabolism, Erciyes University Medical School, 38039 Kayseri, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Tanriverdi
authors.affiliation: Department of Endocrinology and Metabolism, Erciyes University Medical School, 38039 Kayseri, Turkey.
authors.forename: Kursad
authors.initials: K
authors.lastname: Unluhizarci
authors.affiliation: Department of Internal Medicine, Erciyes University Medical School, Kayseri, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Sungur
authors.affiliation: Department of Infectious Diseases, Erciyes University Medical School, Kayseri, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Doganay
authors.affiliation: Department of Endocrinology and Metabolism, Erciyes University Medical School, 38039 Kayseri, Turkey.
authors.forename: Fahrettin
authors.initials: F
authors.lastname: Kelestimur
keywords: ACTH stimulation test; Calculated free cortisol; HPA axis; Salivary cortisol; Severe sepsis; Total cortisol