A comparison of the use of urinary cortisol to creatinine ratios and nocturnal salivary cortisol in the evaluation of cyclicity in patients with Cushing's syndrome

J Clin Endocrinol Metab. 2013 Jan;98(1):E72-6. doi: 10.1210/jc.2012-2925. Epub 2012 Nov 12.


Context: Cyclical Cushing's syndrome is detected in our center by collecting sequential early morning urine (EMU) samples for cortisol to creatinine ratio over 28 d. The Endocrine Society suggests that nocturnal salivary cortisol (NSC) may be used to assess patients for cyclical Cushing's. However, there is only very limited evidence that it correlates with EMU testing or that it demonstrates cycling over 28 d.

Objective: We sought to correlate NSC with EMU results collected the following morning and to determine whether NSC could be used to detect cyclical Cushing's.

Design and setting: An observation study of 28-d collections for NSC and EMU was performed in a tertiary referral center over 1 yr.

Patients: A 28-d collection of NSC and EMU was performed in 10 patients with confirmed or suspected Cushing's syndrome.

Main outcome measure: The main outcome of the study was the correlation of salivary and urinary cortisol with graphical assessment of results for cycling.

Results: Eleven collections were performed. One patient with cyclical Cushing's completed the collection before and after cabergoline therapy. Two hundred seventy matched salivary and urinary results were correlated (r = 0.79; P < 0.001). In two patients with cyclical Cushing's, EMU and NSC followed a similar cyclical pattern. In one patient with recurrent cyclical Cushing's, cortisol was elevated in both saliva and urine but with more prominent cycles in saliva.

Conclusion: NSC correlated well with EMU. NSC detected all cases of cyclical Cushing's. Therefore, NSC may prove to be an additional option or replacement for EMU in detecting cyclical Cushing's syndrome.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Circadian Rhythm / physiology
  • Creatinine / urine*
  • Cushing Syndrome / diagnosis*
  • Cushing Syndrome / metabolism
  • Cushing Syndrome / urine
  • Disease Progression
  • Female
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / metabolism*
  • Hydrocortisone / urine*
  • Male
  • Middle Aged
  • Periodicity
  • Prognosis
  • Saliva / chemistry
  • Saliva / metabolism*
  • Young Adult


  • Creatinine
  • Hydrocortisone