Cutoff values of midnight salivary cortisol for the diagnosis of overt hypercortisolism are highly influenced by methods

Clin Chim Acta. 2010 Mar;411(5-6):364-7. doi: 10.1016/j.cca.2009.11.033. Epub 2009 Dec 5.


Background: Midnight salivary cortisol (MSC) concentration has been considered as a sensitive marker of overt hypercortisolism. Because no studies on commercially available automated, non-isotopic MSC assays have been reported, we determined and compared the diagnostic performance of an automated electrochemiluminescent immunoassay (ECLIA, Elecsys E170) and an in-house radioimmunoassay (RIA) for MSC measurement.

Methods: The study involved 126 consecutive patients referred for evaluation because of symptoms of Cushing's syndrome, obesity, or the presence of incidentally discovered adrenal adenoma. Using detailed clinical, hormonal and radiological evaluation overt endogenous hypercortisolism was confirmed in 9 patients and was excluded in 117 patients.

Results: ROC analysis indicated that the best performance of MSC was obtained at cutoff value of 0.35 microg/dl using ECLIA (sensitivity, 100%; specificity, 88%) and 0.29 microg/dl (sensitivity, 100%; specificity, 71%) using RIA. When the findings were compared to those obtained from low dose dexamethasone test, both ECLIA and RIA of MSC showed a better diagnostic performance.

Conclusion: MSC measurement is useful for the diagnosis of overt hypercortisolism but the cutoff value is highly dependent on the method used. We recommend the use of automated ECLIA for MSC assay, and we propose further studies on other automated immunoassay analyzers potentially suitable for MSC measurements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / diagnosis*
  • Adrenocortical Adenoma / diagnosis*
  • Adult
  • Biomarkers / blood
  • Cushing Syndrome / diagnosis*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Male
  • Obesity / diagnosis*
  • ROC Curve
  • Radioimmunoassay
  • Reproducibility of Results
  • Saliva / chemistry*
  • Sensitivity and Specificity


  • Biomarkers
  • Hydrocortisone