Skip to main content

Advertisement

SpringerLink
Log in

Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing’s syndrome

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

This study estimates diagnostic performance of late-night salivary cortisol (LNSC) as measured by automated electrochemiluminescence immunoassay (ECLIA), evaluates the clinical implication of two consecutive LNSC measurements, and compares its accuracy with enzyme-linked immunosorbent assay (ELISA) and serum cortisol after low-dose dexamethasone suppression test (DST) in obese and overweight patients referred for suspected Cushing’s syndrome (CS). One hundred twenty three consecutive obese and overweight referred patients and 98 healthy volunteers provided two saliva samples collected at 23:00 using a Salivette (Sarstedt, Germany), assayed by ECLIA (Cobas e601) and ELISA. The patients underwent DST and were further evaluated until CS was pathologically confirmed (n = 45) or excluded. Diagnostic performance of LNSC was evaluated by receiver operating characteristic (ROC) analysis. The total areas under the curve (AUC) were calculated to compare the different tests. We found that a cut-off value of 9.4 nmol/l can differentiate CS among obese and overweight patients with sensitivity of 84.4 % (95% CI 71.2–92.2), specificity of 92.3 % (95% CI 84.2–96.4), and diagnostic odds ratio of 65.1 (95% CI 20.4–207.6). No difference was found between AUCs from the first, second, and the mean from the two LNSC measurements (ECLIA), LNSC (ELISA), or DST. The single LNSC (ECLIA) and DST improved the sensitivity and specificity for concordant results up to 100 and 97.4 %, respectively. In conclusion, due to its automation and its comparable diagnostic performance, ECLIA is preferable as a first-line LNSC screening test for CS. The initial use of single LNSC followed by DST provides better diagnostic performance for concordant results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References:

  1. C. Steffensen, A.M. Bak, K.Z. Rubeck, J.O.L. Jorgensen, Epidemiology of Cushing’s syndrome. Neuroendocrinology 92(1), 1–5 (2010)

    Article  PubMed  CAS  Google Scholar 

  2. B. Catargi, V. Rigalleau, A. Poussin, N. Ronci-Chaix, V. Bex, V. Vergnot, H. Gin, P. Roger, A. Tabarin, Occult Cushing’s syndrome in type-2 diabetes. J. Clin. Endocrinol. Metab. 88, 5808–5813 (2003)

    Article  PubMed  CAS  Google Scholar 

  3. G. Leibowitz, A. Tsur, S.D. Chayen, M. Salameh, I. Raz, E. Cerasi, D.J. Gross, Pre-clinical Cushing’s syndrome an unexpected frequent cause of poor glycemic control in obese diabetic patients. Clin. Endocrinol. (Oxf). 44, 712–722 (1996)

    Article  Google Scholar 

  4. M. Omura, K. Yamaguchi, Y. Kakuta, T. Nishikawa, Prospective study on the prevalence of secondary hypertension among hypertensive patients visiting a general outpatient clinic in Japan. Hypertens. Res. 27, 193–202 (2004)

    Article  PubMed  Google Scholar 

  5. I. Chiodini, M.L. Mascia, S. Muscarella, C. Battista, S. Minisola, M. Arosio, S.A. Santini, G. Guglielmi, V. Garnevale, A. Scillitani, Subclinical hypercortisolism among outpatients referred for osteoporosis. Ann. Intern. Med. 147, 541–548 (2007)

    PubMed  Google Scholar 

  6. I. Chiodini, M. Torlontano, A. Scillitani, M. Arosio, S. Bacci, S. Di Lembo, P. Epaminonda, G. Augello, R. Enrini, B. Ambrosi, G. Adda, V. Trischitta, Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case–control study in hospitalized patients. Eur. J. Endocrinol. 153, 837–844 (2005)

    Article  PubMed  CAS  Google Scholar 

  7. C. Davenport, A. Liew, B. Doherty, H.H.N. Win, H. Misran, S. Hanna, D. Kealy, F. Al-Nooh, A. Agha, C.J. Thompson, M. Lee, D. Smith, The prevalence of adrenal incidentaloma in routine clinical practice. Endocrine 40, 80–83 (2011)

    Article  PubMed  CAS  Google Scholar 

  8. D.A. Vassiliadi, G. Ntali, T. Stratigou, M. Adali, S. Tsagarakis, Abberant cortisol responses to physiological stimuli in patients presenting with bilateral adrenal incidentalomas. Endocrine 40, 437–444 (2011)

    Article  PubMed  CAS  Google Scholar 

  9. L.K. Nieman, B.M.K. Biller, J.W. Finding, J. Newell-Price, M.O. Savage, P.M. Stewart, V.M. Montori, The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J. Clin Endocrinol Metab. 93, 1526–1540 (2008)

    Article  PubMed  CAS  Google Scholar 

  10. P. Putignano, P. Toja, A. Dubini, P.F. Giraldi, S.M. Corsello, F. Cavaqnini, Midnight salivary cortisol versus urinary free and midnight serum cortisol as screening tests for Cushing’s syndrome. J. Clin. Endocrinol Metab 88, 4153–4157 (2003)

    Article  PubMed  CAS  Google Scholar 

  11. J.P. Kahn, D.R. Rubinov, C.L. Davis, M. Kling, R.M. Post, Salivary cortisol: a practical method for evaluation of adrenal function. Biol. Psychiatry 23, 335–349 (1988)

    Article  PubMed  CAS  Google Scholar 

  12. J. Guechot, J. Fiet, P. Passa, J.M. Villette, B. Gourmel, F. Tabuteau, G. Cathelineau, Dreux C Physiological and pathological variations in saliva cortisol. Horm. Res. 16, 357–364 (1982)

    Article  PubMed  CAS  Google Scholar 

  13. P.J. Evans, J.R. Peters, J. Dyas, R.F. Walker, D. Riad-Fahmy, R. Hall, Salivary cortisol levels in true and apparent hypercortisolism. Clin Endocrinol. (Oxf). 20, 709–715 (1984)

    Article  CAS  Google Scholar 

  14. H. Raff, J.L. Raff, J.W. Finding, Late-night salivary cortisol as a screening test for Cushing’s syndrome. J. Clin. Endocrinol. Metab. 83, 2681–2686 (1998)

    Article  PubMed  CAS  Google Scholar 

  15. D.A. Papanicolaou, N. Mullen, I. Kyrou, L.K. Nieman, Nighttime salivary cortisol: a useful test for the diagnosis of Cushing’s syndrome. J. Clin. Endocrinol. Metab. 87, 4515–4521 (2002)

    Article  PubMed  CAS  Google Scholar 

  16. A. Viardot, P. Huber, J.J. Puder, H. Zulewski, U. Keller, B. Muller, Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free and overnight dexamethasone suppression test. J. Clin. Endocrinol. Metab. 90, 5730–5736 (2005)

    Article  PubMed  CAS  Google Scholar 

  17. S. Kidambi, H. Raff, J.W. Finding, Limitation of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing’s syndrome. Eur. J. Endocrinol. 157, 725–731 (2007)

    Article  PubMed  CAS  Google Scholar 

  18. T. Deutschbein, N. Unger, J. Hinrichs, M.K. Walz, K. Mann, S. Petersen, Late-night and low-dose dexamethasone-suppressed cortisol in saliva and serum for the diagnosis of cortisol-secreting adrenal adenoma. Eur. J. Endocrinol. 161, 747–753 (2009)

    Article  PubMed  CAS  Google Scholar 

  19. S. Sakihara, K. Kageyama, Y. Oki, M. Doi, Y. Iwasaki, S. Takayasu, T. Moriyama, K. Terui, T. Nigawara, Y. Hirata, K. Hashimoto, T. Suda, Evaluation of plasma, salivary, and urinary cortisol levels for diagnosis of Cushing’s syndrome. Endocr. J. 57, 331–337 (2010)

    Article  PubMed  CAS  Google Scholar 

  20. H. Raff, S.L. Ettema, D.C. Eastwood, B.T. Woodson, Salivary cortisol in obstructive sleep apnea: the effect of CPAP. Endocrine 40, 137–139 (2011)

    Article  PubMed  CAS  Google Scholar 

  21. K.I. Alexandraki, A.B. Grossman, Novel insights in the diagnosis of Cushing’s syndrome. Neuroendocrinology 92(1), 35–43 (2010)

    Article  PubMed  CAS  Google Scholar 

  22. S.K. Baid, N. Sinaii, M. Wade, D. Rubino, L.K. Nieman, Radioimmunoassay and tandem mass spectrometry measurement of bedtime salivary cortisol levels: a comparison of assays to establish hypercortisolism. J. Clin. Endocrinol. Metab. 92, 3102–3107 (2007)

    Article  PubMed  CAS  Google Scholar 

  23. G. Beko, I. Varga, E. Glaz, M. Sereg, K. Feldman, M. Toth, K. Racz, A. Patocs, Cutoff values of midnight salivary cortisol for the diagnosis of overt hypercortisolism are highly influenced by methods. Clin. Chim. Acta 411, 364–367 (2010)

    Article  PubMed  CAS  Google Scholar 

  24. S.M. Baid, D. Rubino, N. Sinaii, S. Ramsey, A. Frank, L.K. Nieman, Specificity of screening tests for Cushing’s syndrome in an overweight and obese population. J. Clin. Endocrinol. Metab. 94, 3857–3864 (2009)

    Article  PubMed  CAS  Google Scholar 

  25. M. Boscaro, G. Arnaldi, Approach to the patient with possible Cushing’s syndrome. J. Clin. Endocrinol. Metab. 94, 3121–3131 (2009)

    Article  PubMed  CAS  Google Scholar 

  26. M. Nunes, S. Vattaut, J. Corcuff, A. Rault, H. Loiseau, B. Gatta, N. Valli, L. Letenneur, A. Tabarin, Late-night salivary cortisol for diagnosis of overt and subclinical Cushing’s syndrome in hospitalized and ambulatory patients. J. Clin. Endocrinol. Metab. 94, 456–462 (2009)

    Article  PubMed  CAS  Google Scholar 

  27. K.H. Zou, J. O’Maley, L. Mauri, Receiver-operating characteristic analysis for evaluating diagnostic tests and predictive models. Circulation 115, 654–657 (2007)

    Article  PubMed  Google Scholar 

  28. O Ajetunmobi, Making sense of critical appraisal (Hodder Arnold part of Hachette, London, 2002). pp. 69–84

  29. J.A. Hanley, B.J. McNeil, The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 143, 29–36 (1982)

    PubMed  CAS  Google Scholar 

  30. J.A. Hanley, B.J. McNeil, A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 148, 839–843 (1983)

    PubMed  CAS  Google Scholar 

  31. K. Jeyaraman, A.C. Amini, G. Nandita, S.N. Dwivedi, Late-night salivary cortisol in normal subjects and in patients with Cushing’s syndrome. Postgrad Med J. 86, 399–404 (2010)

    Article  PubMed  CAS  Google Scholar 

  32. C. Carrozza, S.M. Corsello, R.M. Paragliola, F.I.S. Palumbo, P. Locantore, A. Sferrazza, A. Pontecorvi, C. Zuppi, Clinical accuracy of midnight salivary cortisol measured by automated electrochemiluminescence immunoassay method in Cushing’s syndrome. Ann. Clin. Biochem. 47, 228–232 (2010)

    Article  PubMed  CAS  Google Scholar 

  33. M. Yaneva, G. Kirilov, S. Zacharieva, Midnight salivary cortisol, measured by highly sensitive electrochemiluminescene immunoassay, for the diagnosis of Cushing’s syndrome. Cent. Eur. J. Med. 4, 59–64 (2009)

    Article  CAS  Google Scholar 

  34. M. Sereg, J. Toke, A. Patocs, I. Varga, P. Igaz, N. Szucs, J Horanyi, P. Pusztai, S. Czirjak, E. Glaz, K. Racz, M. Toth, Diagnostic performance of salivary cortisol and serum osteocalcin measurements in patients with overt and subclinical Cushing’s syndrome. Steroids. 76, 38–42 (2011)

    Google Scholar 

  35. M. Vogeser, J. Durner, E. Seliger, C. Auernhammer, Measurement of late-night salivary cortisol with an automated immunoassay system. Clin. Chem. Lab. Med. 44, 1441–1445 (2006)

    Article  PubMed  CAS  Google Scholar 

  36. CA Carrasco, M Garcia, M Goycoolea, J Cerda, J Berherat, O. Padilla, D. Meza, N. Wohllk, T Quiroga, Reproducibility and performance of one or two samples of salivary cortisol in the diagnosis of Cushing’s syndrome using an automated immunoassay system. Endocrine. (2012). doi:10.1007/s12020-012-9597-z

Download references

Acknowledgments

This work was supported by the Presidential Grant no. MК-6978.201

Disclosure

The authors have nothing to disclose.

Author information

Authors and Affiliations

  1. The National Research Center for Endocrinology, Dmitria Uljanova, 11, Moscow, Russia, 117036

    Zhanna E. Belaya, Alexander V. Iljin, Galina A. Melnichenko, Liudmila Y. Rozhinskaya, Natalia V. Dragunova, Larisa K. Dzeranova, Svetlana A. Butrova, Ekaterina A. Troshina & Ivan I. Dedov

Authors
  1. Zhanna E. Belaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander V. Iljin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Galina A. Melnichenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liudmila Y. Rozhinskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Natalia V. Dragunova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Larisa K. Dzeranova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Svetlana A. Butrova
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ekaterina A. Troshina
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ivan I. Dedov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhanna E. Belaya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belaya, Z.E., Iljin, A.V., Melnichenko, G.A. et al. Diagnostic performance of late-night salivary cortisol measured by automated electrochemiluminescence immunoassay in obese and overweight patients referred to exclude Cushing’s syndrome. Endocrine 41, 494–500 (2012). https://doi.org/10.1007/s12020-012-9658-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9658-3

Keywords

Search

Navigation