Comparison of total, salivary and calculated free cortisol levels in patients with severe sepsis

Gulsah Elbuken, Zuleyha Karaca, Fatih Tanriverdi, Kursad Unluhizarci, Murat Sungur, Mehmet Doganay, Fahrettin Kelestimur, Gulsah Elbuken, Zuleyha Karaca, Fatih Tanriverdi, Kursad Unluhizarci, Murat Sungur, Mehmet Doganay, Fahrettin Kelestimur

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.

Trial registration: ClinicalTrials.gov No: NCT02589431.

Keywords: ACTH stimulation test; Calculated free cortisol; HPA axis; Salivary cortisol; Severe sepsis; Total cortisol.

Figures

Fig. 1
Fig. 1
Patient enrollment
Fig. 2
Fig. 2
Correlations between STC, SaC and cFC in baseline and stimulated conditions

References

    1. Venkatesh B, Cohen J, Hickman I, Nisbet J, Thomas P, Ward G, et al. Evidence of altered cortisol metabolism in critically ill patients: a prospective study. Intensive Care Med. 2007;33(10):1746–53. doi: 10.1007/s00134-007-0727-7.
    1. Venkataraman S, Munoz R, Candido C, Witchel SF. The hypothalamic-pituitary-adrenal axis in critical illness. Rev Endocr Metab Disord. 2007;8(4):365–73. doi: 10.1007/s11154-007-9058-9.
    1. Annane D, Bellissant E. Prognostic value of cortisol response in septic shock. JAMA. 2000;284(3):308–9. doi: 10.1001/jama.284.3.308.
    1. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350(16):1629–38. doi: 10.1056/NEJMoa020266.
    1. Widmer IE, Puder JJ, König C, Pargger H, Zerkowski HR, Girard J, et al. Cortisol response in relation to the severity of stress and illness. J Clin Endocrinol Metab. 2005;90(8):4579–86. doi: 10.1210/jc.2005-0354.
    1. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36(6):1937–49. doi: 10.1097/CCM.0b013e31817603ba.
    1. Rothwell PM, Lawler PG. Prediction of outcome in intensive care patients using endocrine parameters. Crit Care Med. 1995;23(1):78–83. doi: 10.1097/00003246-199501000-00015.
    1. Streeten DH. What test for hypothalamic-pituitary-adrenocortical insufficiency? Lancet. 1999;354(9174):179–80. doi: 10.1016/S0140-6736(98)00318-3.
    1. Annane D, Maxime V, Ibrahim F, Alvarez JC, Abe E, Boudou P. Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med. 2006;174(12):1319–26. doi: 10.1164/rccm.200509-1369OC.
    1. Dickstein G. High-dose and low-dose cosyntropin stimulation tests for diagnosis of adrenal insufficiency. Ann Intern Med. 2004;140(4):312–3. doi: 10.7326/0003-4819-140-4-200402170-00026.
    1. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003;348(8):727–34. doi: 10.1056/NEJMra020529.
    1. Hammond GL, Smith CL, Underhill DA. Molecular studies of corticosteroid binding globulin structure, biosynthesis and function. J Steroid Biochem Mol Biol. 1991;40(4–6):755–62. doi: 10.1016/0960-0760(91)90300-T.
    1. Coolens JL, Van Baelen H, Heyns W. Clinical use of unbound plasma cortisol as calculated from total cortisol and corticosteroid-binding globulin. J Steroid Biochem. 1987;26(2):197–202. doi: 10.1016/0022-4731(87)90071-9.
    1. Ho JT, Al-Musalhi H, Chapman MJ, Quach T, Thomas PD, Bagley CJ, et al. Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab. 2006;91(1):105–14. doi: 10.1210/jc.2005-0265.
    1. 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(8):2965–71. doi: 10.1210/jc.2007-0181.
    1. Cohen J, Venkatesh B, Galligan J, Thomas P. Salivary cortisol concentration in the intensive care population: correlation with plasma cortisol values. Anaesth Intensive Care. 2004;32(6):843–5.
    1. Gozansky WS, Lynn JS, Laudenslager ML, Kohrt WM. Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-pituitary-adrenal axis activity. Clin Endocrinol (Oxf) 2005;63(3):336–41. doi: 10.1111/j.1365-2265.2005.02349.x.
    1. Schindhelm RK, van de Leur JJ, Rondeel JM. Salivary cortisol as an alternative for serum cortisol in the low-dose adrenocorticotropic hormone stimulation test? J Endocrinol Invest. 2010;33(2):92–5. doi: 10.1007/BF03346560.
    1. Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol in saliva and serum in comparison with the insulin tolerance test. Horm Metab Res. 2009;41(11):834–9. doi: 10.1055/s-0029-1225630.
    1. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. 1992;136(5 Suppl):e28.
    1. Karaca Z, Lale A, Tanriverdi F, Kula M, Unluhizarci K, Kelestimur F. The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary. 2011;14(2):134–40. doi: 10.1007/s11102-010-0270-3.
    1. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29. doi: 10.1097/00003246-198510000-00009.
    1. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, et al. (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10. doi: 10.1007/BF01709751.
    1. Topkas E, Keith P, Dimeski G, Cooper-White J, Punyadeera C. Evaluation of saliva collection devices for the analysis of proteins. Clin Chim Acta. 2012;413(13–14):1066–70. doi: 10.1016/j.cca.2012.02.020.
    1. Yildiz O, Tanriverdi F, Simsek S, Aygen B, Kelestimur F. The effects of moderate-dose steroid therapy in sepsis: a placebo-controlled, randomized study. J Res Med Sci. 2011;16(11):1410–21.
    1. Aygen B, Inan M, Doganay M, Keleştimur F. Adrenal functions in patients with sepsis. Exp Clin Endocrinol Diabetes. 1997;105(3):182–6. doi: 10.1055/s-0029-1211749.
    1. Venkatesh B, Mortimer RH, Couchman B, Hall J. Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study. Anaesth Intensive Care. 2005;33(2):201–9.
    1. Jenkins RC, Ross RJM. The endocrinology of the critically ill: current opinion. Curr Opin Endocrinol Diab. 1996;3:138–45. doi: 10.1097/00060793-199604000-00011.
    1. Yildiz O, Doganay M, Aygen B, Güven M, Keleştimur F, Tutus A. Physiological-dose steroid therapy in sepsis. Crit Care. 2002;6(3):251–9. doi: 10.1186/cc1498.
    1. Beishuizen A, Thijs LG, Vermes I. Patterns of corticosteroid binding globulin and the free cortisol index during septic shock and multitrauma. Intensive Care Med. 2001;27(10):1584–91. doi: 10.1007/s001340101073.
    1. Lin HY, Muller YA, Hammond GL. Molecular and structural basis of steroid hormone binding and release from corticosteroid-binding globulin. Mol Cell Endocrinol. 2010;316(1):3–12. doi: 10.1016/j.mce.2009.06.015.
    1. Aardal E, Holm AC. Cortisol in saliva-reference ranges and relation to cortisol in serum. Eur J Clin Chem Clin Biochem. 1995;33(12):927–32.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi