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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter


IMPACT FACTOR 2018: 3.638

CiteScore 2018: 2.44

SCImago Journal Rank (SJR) 2018: 1.191
Source Normalized Impact per Paper (SNIP) 2018: 1.205

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1437-4331
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Volume 53, Issue 9

Issues

Different methods to estimate serum free cortisol: a comparison during cortisol tetracosactide testing

Julie Brossaud / Blandine Gatta / Antoine Tabarin / Jean-Benoît Corcuff
Published Online: 2014-11-07 | DOI: https://doi.org/10.1515/cclm-2014-0912

Abstract

Background: Serum cortisol is routinely quantified by immunoassays. In intensive care units serum free cortisol (FC) determination has been described as a better indicator of survival than total cortisol (TC). To estimate FC different methods are available including saliva sampling. We compared five methods to estimate FC, before and after an ACTH stimulating test in patients suspected of adrenal insufficiency.

Method: Serum and saliva was collected from 130 patients from the Endocrine Department of a university hospital before and after tetracosactide injection for TC determination. FC was estimated: after serum ultrafiltration, quadratic (Coolens’) or cubic (Dorin’s) equations, using TC/cortisol-binding globulin concentrations ratio or using cortisol concentration determination in saliva.

Results: FC concentrations obtained by different techniques were significantly correlated and Passing-Bablok regressions showed no deviation from linearity between salFC and filtFC or quadFC. Using the routine assumption that the patients were correctly diagnosed using a post-tetracosactide TC threshold of 550 nmol/L the FC methods generating the best ROC curves were salFC and filtFC or cubFC 30 min after tetracosactide injection.

Conclusions: FC concentrations obtained by different techniques are significantly but not similarly correlated with TC. As, salFC and filtFC are more convenient to perform than methods involving CBG assays and are better correlated to TC during tetracosactide tests they may be preferred as FC surrogate assays.

This article offers supplementary material which is provided at the end of the article.

Keywords: free serum cortisol; saliva cortisol; tetraco- sactide

References

  • 1.

    Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989;10:232–74.CrossrefPubMedGoogle Scholar

  • 2.

    Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab 2006;91:3725–45.CrossrefPubMedGoogle Scholar

  • 3.

    Vogeser M, Briegel J. Free cortisol and critically ill patients. N Engl J Med 2004;351:395–7; author reply 395–7.Google Scholar

  • 4.

    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.Google Scholar

  • 5.

    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;63:336–41.CrossrefGoogle Scholar

  • 6.

    Contreras LN, Arregger AL, Persi GG, Gonzalez NS, Cardoso EM. A new less-invasive and more informative low-dose ACTH test: salivary steroids in response to intramuscular corticotrophin. Clin Endocrinol (Oxf) 2004;61:675–82.CrossrefGoogle Scholar

  • 7.

    Marcus-Perlman Y, Tordjman K, Greenman Y, Limor R, Shenkerman G, Osher E, et al. Low-dose ACTH (1 microg) salivary test: a potential alternative to the classical blood test. Clin Endocrinol (Oxf) 2006;64:215–8.Google Scholar

  • 8.

    Perogamvros I, Owen LJ, Keevil BG, Brabant G, Trainer PJ. Measurement of salivary cortisol with liquid chromatography-tandem mass spectrometry in patients undergoing dynamic endocrine testing. Clin Endocrinol (Oxf) 2010;72:17–21.Google Scholar

  • 9.

    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.Web of ScienceCrossrefPubMedGoogle Scholar

  • 10.

    Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test. Eur J Endocrinol 2009;160:9–16.Google Scholar

  • 11.

    Šimůnková K, Hampl R, Hill M, Doucha J, Stárka L, Vondra K. Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol. Physiol Res 2007;56:449–53.Google Scholar

  • 12.

    Cetinkaya S, Ozon A, Yordam N. Diagnostic value of salivary cortisol in children with abnormal adrenal cortex functions. Horm Res 2007;67:301–6.Web of ScienceGoogle Scholar

  • 13.

    Chu FW, Ekins RP. Detection of corticosteroid binding globulin in parotid fluids: evidence for the presence of both protein-bound and non-protein-bound (free) steroids in uncontaminated saliva. Acta Endocrinol (Copenh) 1988;119:56–60.Google Scholar

  • 14.

    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.Web of ScienceGoogle Scholar

  • 15.

    Morelius E, Nelson N, Theodorsson E. Saliva collection using cotton buds with wooden sticks: a note of caution. Scand J Clin Lab Invest 2006;66:15–8.Google Scholar

  • 16.

    Brien TG. Pathophysiology of free cortisol in plasma. Ann N Y Acad Sci 1988;538:130–6.Google Scholar

  • 17.

    Vogeser M, Mohnle P, Briegel J. Free serum cortisol: quantification applying equilibrium dialysis or ultrafiltration and an automated immunoassay system. Clin Chem Lab Med 2007;45:521–5.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 18.

    Vogeser M, Briegel J. Effect of temperature on protein binding of cortisol. Clin Biochem 2007;40:724–7.CrossrefPubMedGoogle Scholar

  • 19.

    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;26:197–202.PubMedCrossrefGoogle Scholar

  • 20.

    Dorin RI, Pai HK, Ho JT, Lewis JG, Torpy DJ, Urban FK, 3rd, et al. Validation of a simple method of estimating plasma free cortisol: role of cortisol binding to albumin. Clin Biochem 2009;42:64–71.Web of ScienceGoogle Scholar

  • 21.

    Pemberton PA, Stein PE, Pepys MB, Potter JM, Carrell RW. Hormone binding globulins undergo serpin conformational change in inflammation. Nature 1988;336:257–8.Google Scholar

  • 22.

    Hammond GL, Smith CL, Paterson NA, Sibbald WJ. A role for corticosteroid-binding globulin in delivery of cortisol to activated neutrophils. J Clin Endocrinol Metab 1990;71:34–9.CrossrefPubMedGoogle Scholar

  • 23.

    Turpeinen U, Hamalainen E. Determination of cortisol in serum, saliva and urine. Best Pract Res Clin Endocrinol Metab 2013;27:795–801.CrossrefPubMedGoogle Scholar

  • 24.

    Oelkers W. Adrenal insufficiency. N Engl J Med 1996;335: 1206–12.Google Scholar

  • 25.

    Duclos M, Corcuff JB, Arsac L, Moreau-Gaudry F, Rashedi M, Roger P, et al. Corticotroph axis sensitivity after exercise in endurance-trained athletes. Clin Endocrinol (Oxf) 1998;48: 493–501.CrossrefGoogle Scholar

  • 26.

    Clark PM, Neylon I, Raggatt PR, Sheppard MC, Stewart PM. Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders. Clin Endocrinol (Oxf) 1998;49:287–92.CrossrefGoogle Scholar

  • 27.

    Vogeser M, Briegel J, Zachoval R. Dialyzable free cortisol after stimulation with Synacthen. Clin Biochem 2002;35:539–43.PubMedCrossrefGoogle Scholar

  • 28.

    Vialard-Miguel J, Belaidi N, Lembeye L, Corcuff JB. Lemon juice alters cortisol assays in saliva. Clin Endocrinol (Oxf) 2005;63:478–9.Google Scholar

  • 29.

    Umeda T, Hiramatsu R, Iwaoka T, Shimada T, Miura F, Sato T. Use of saliva for monitoring unbound free cortisol levels in serum. Clin Chim Acta 1981;110:245–53.Google Scholar

  • 30.

    Lewis JG, Elder PA. Intact or ‘active’ corticosteroid-binding globulin (CBG) and total CBG in plasma: determination by parallel ELISAs using monoclonal antibodies. Clin Chim Acta 2013;416:26–30.Web of ScienceGoogle Scholar

  • 31.

    Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Salivary cortisol: a better measure of adrenal cortical function than serum cortisol. Ann Clin Biochem 1983;20(Pt 6):329–35.PubMedCrossrefGoogle Scholar

  • 32.

    Kerlik J, Penesova A, Vlcek M, Imrich R, Vogeser M, Radikova Z. Comparison of salivary cortisol and calculated free plasma cortisol during low-dose ACTH test in healthy subjects. Clin Biochem 2010;43:764–7.Web of SciencePubMedCrossrefGoogle Scholar

  • 33.

    Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004;350:1629–38.Google Scholar

  • 34.

    Dhillo WS, Kong WM, Le Roux CW, Alaghband-Zadeh J, Jones J, Carter G, et al. Cortisol-binding globulin is important in the interpretation of dynamic tests of the hypothalamic-pituitary-adrenal axis. Eur J Endocrinol 2002;146:231–5.Google Scholar

  • 35.

    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;91:105–14.Google Scholar

  • 36.

    Gupta A, Cheetham T, Jaffray C, Ullman D, Gibb I, Spencer DA. Repeatability of the low-dose ACTH test in asthmatic children on inhaled corticosteroids. Acta Paediatr 2009;98:1945–9.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 37.

    Kahn SE, Maxwell JU, Barron JL. Salivary cortisol assessment in the evaluation of hypothalamic-pituitary-adrenal function. S Afr Med J 1984;65:843–6.PubMedGoogle Scholar

  • 38.

    Oelkers W. Clinical diagnosis of hyper- and hypocortisolism. Noise Health 2000;2:39–48.PubMedGoogle Scholar

  • 39.

    Abdu TA, Elhadd TA, Neary R, Clayton RN. Comparison of the low dose short synacthen test (1 microg), the conventional dose short synacthen test (250 microg), and the insulin tolerance test for assessment of the hypothalamo-pituitary-adrenal axis in patients with pituitary disease. J Clin Endocrinol Metab 1999;84:838–43.Google Scholar

  • 40.

    Soule S, Van Zyl Smit C, Parolis G, Attenborough S, Peter D, Kinvig S, et al. The low dose ACTH stimulation test is less sensitive than the overnight metyrapone test for the diagnosis of secondary hypoadrenalism. Clin Endocrinol (Oxf) 2000;53:221–7.Google Scholar

  • 41.

    Šimůnková K, Stárka L, Hill M, Kříž L, Hampl R, Vondra K. Comparison of total and salivary cortisol in a low-dose ACTH (Synacthen) test: influence of three-month oral contraceptives administration to healthy women. Physiol Res 2008;57(Suppl 1): S193–9.Google Scholar

  • 42.

    Kirschbaum C, Kudielka BM, Gaab J, Schommer NC, Hellhammer DH. Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosom Med 1999;61:154–62.PubMedCrossrefGoogle Scholar

  • 43.

    Inder WJ, Dimeski G, Russell A. Measurement of salivary cortisol in 2012 – laboratory techniques and clinical indications. Clin Endocrinol (Oxf) 2012;77:645–51.Web of ScienceGoogle Scholar

  • 44.

    Pretorius CJ, Galligan JP, McWhinney BC, Briscoe SE, Ungerer JP. Free cortisol method comparison: ultrafiltation, equilibrium dialysis, tracer dilution, tandem mass spectrometry and calculated free cortisol. Clin Chim Acta 2011;412:1043–7.Web of ScienceGoogle Scholar

About the article

Corresponding author: Dr. Jean-Benoît Corcuff, Service de Médecine Nucléaire, Hôpital Haut-Lévêque, 33604 Pessac, France, Phone: +33 556 656825, Fax: +33 556 656839, E-mail:


Received: 2014-09-16

Accepted: 2014-10-20

Published Online: 2014-11-07

Published in Print: 2015-08-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), Volume 53, Issue 9, Pages 1367–1373, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2014-0912.

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