Acute Crit Care.  2020 Aug;35(3):149-155. 10.4266/acc.2020.00297.

Comparison of salivary and serum cortisol levels in mechanically ventilated patients and non-critically ill patients

  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
  • 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, Korea


Although the measuring free cortisol is ideal for assessment of hypothalamicpituitary-adrenal function, it is not routinely measured. Salivary cortisol correlates well with the biologically active free cortisol. Therefore, this study measured the morning basal as well as adrenocorticotropic hormone-stimulated salivary cortisol levels in mechanically ventilated patients and compared the results with non-critically ill patients.
We prospectively enrolled 49 mechanically ventilated patients and 120 patients from the outpatient clinic. Serum and saliva samples were collected between 8 AM and 10 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit. The salivary samples were insufficient in 15 mechanically ventilated patients (30.6%), and these patients were excluded from the final analysis.
Mechanically ventilated patients (n=34) were significantly older and had lower body mass index and serum albumin levels and higher serum creatinine levels than non-critically ill patients (n = 120). After adjustment for these parameters, both basal and stimulated salivary and serum cortisol levels were higher in mechanically ventilated patients. The increase in cortisol was not significantly different between the two groups. Serum cortisol levels showed a positive correlation with salivary cortisol levels. Among mechanically ventilated patients, both basal serum and salivary cortisol levels were lower in survivors than in non-survivors.
Both basal total serum and salivary cortisol levels were elevated in mechanically ventilated patients and in non-survivors.


cortisol; hydrocortisone; intensive care units; outpatients; saliva; stress


  • Figure 1. Flowchart of study participants in the intensive care unit (ICU).

  • Figure 2. Scatter plot between basal (A) or stimulated serum (B) and salivary cortisol levels.


1. Téblick A, Peeters B, Langouche L, Van den Berghe G. Adrenal function and dysfunction in critically ill patients. Nat Rev Endocrinol. 2019; 15:417–27.
2. Annane D, Pastores SM, Rochwerg B, Arlt W, Balk RA, Beishuizen A, et al. Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Intensive Care Med. 2017; 43:1751–63.
3. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004; 350:1629–38.
4. Raff H. Utility of salivary cortisol measurements in Cushing’s syndrome and adrenal insufficiency. J Clin Endocrinol Metab. 2009; 94:3647–55.
5. Aardal-Eriksson E, Karlberg BE, Holm AC. Salivary cortisol: an alternative to serum cortisol determinations in dynamic function tests. Clin Chem Lab Med. 1998; 36:215–22.
6. Perogamvros I, Keevil BG, Ray DW, Trainer PJ. Salivary cortisone is a potential biomarker for serum free cortisol. J Clin Endocrinol Metab. 2010; 95:4951–8.
7. Aardal E, Holm AC. Cortisol in saliva: reference ranges and relation to cortisol in serum. Eur J Clin Chem Clin Biochem. 1995; 33:927–32.
8. Levy-Shraga Y, Pinhas-Hamiel O, Molina-Hazan V, Tamir-Hostovsky L, Eini ZM, Lerner-Geva L, et al. Elevated baseline cortisol levels are predictive of bad outcomes in critically ill children. Pediatr Emerg Care. 2018; 34:613–7.
9. Bekhit OE, Mohamed SA, Yousef RM, AbdelRasol HA, Khalaf NA, Salah F. Relation between baseline total serum cortisol level and outcome in pediatric intensive care unit. Sci Rep. 2019; 9:6008.
10. Vassiliadi DA, Dimopoulou I, Tzanela M, Douka E, Livaditi O, Orfanos SE, et al. Longitudinal assessment of adrenal function in the early and prolonged phases of critical illness in septic patients: relations to cytokine levels and outcome. J Clin Endocrinol Metab. 2014; 99:4471–80.
11. Pandya U, Polite N, Wood T, Lieber M. Increased total serum random cortisol levels predict mortality in critically ill trauma patients. Am Surg. 2014; 80:1112–8.
12. Mello RC, Sad EF, Andrade BC, Neves SP, Santos SM, Sarquis MM, et al. Serum and salivary cortisol in the diagnosis of adrenal insufficiency and as a predictor of the outcome in patients with severe sepsis. Arq Bras Endocrinol Metabol. 2011; 55:455–9.
13. Elbuken G, Karaca Z, Tanriverdi F, Unluhizarci K, Sungur M, Doganay M, et al. Comparison of total, salivary and calculated free cortisol levels in patients with severe sepsis. J Intensive Care. 2016; 4:3.
14. Arafah BM, Nishiyama FJ, Tlaygeh H, Hejal R. Measurement of salivary cortisol concentration in the assessment of adrenal function in critically ill subjects: a surrogate marker of the circulating free cortisol. J Clin Endocrinol Metab. 2007; 92:2965–71.
15. Estrada-Y-Martin RM, Orlander PR. Salivary cortisol can replace free serum cortisol measurements in patients with septic shock. Chest. 2011; 140:1216–22.
16. Raff H, Brock S, Findling JW. Cosyntropin-stimulated salivary cortisol in hospitalized patients with hypoproteinemia. Endocrine. 2008; 34:68–74.
17. Puglisi S, Pizzuto A, Laface B, Panero F, Aprà F, Palmas E, et al. Determination of salivary cortisol to assess time-related changes of the adrenal response to stress in critically ill patients. Eur J Intern Med. 2019; 68:66–70.
18. Bartanusz V, Corneille MG, Sordo S, Gildea M, Michalek JE, Nair PV, et al. Diurnal salivary cortisol measurement in the neurosurgical-surgical intensive care unit in critically ill acute trauma patients. J Clin Neurosci. 2014; 21:2150–4.
19. Duplessis C, Rascona D, Cullum M, Yeung E. Salivary and free serum cortisol evaluation. Mil Med. 2010; 175:340–6.
20. Bruno JJ, Hernandez M, Ghosh S, Pravinkumar SE. Critical illness-related corticosteroid insufficiency in cancer patients. Support Care Cancer. 2012; 20:1159–67.
21. Salluh JI, Shinotsuka CR, Soares M, Bozza FA, Lapa e Silva JR, Tura BR, et al. Cortisol levels and adrenal response in severe community-acquired pneumonia: a systematic review of the literature. J Crit Care. 2010; 25:541.e1–8.
22. Song JH, Kim JH, Lee SM, Lee J. Prognostic implication of adrenocortical response during the course of critical illness. Acute Crit Care. 2019; 34:38–45.
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