Performance of salivary cortisol in the diagnosis of Cushing's syndrome, adrenal incidentaloma, and adrenal insufficiency

Abstract

Objective: Salivary cortisol has recently been suggested for studies on the hypothalamic-pituitaryadrenal (HPA) axis. The lack of circadian rhythm is a marker of Cushing's syndrome (CS), and some authors have reported that low salivary cortisol levels may be a marker of adrenal insufficiency. The aim of our study was to define the role of salivary cortisol in specific diagnostic settings of HPA axis disease. Subjects and methods: We analyzed morning salivary cortisol (MSC) and late-night salivary cortisol (LNSC) levels in 406 subjects: 52 patients with Cushing's disease (CD), 13 with ectopic CS, 17 with adrenal CS, 27 with CD in remission (a mean follow-up of 66G39 months), 45 with adrenal incidentaloma, 73 assessed as having CS and then ruled out for endogenous hypercortisolism, 75 with adrenal insufficiency, and 104 healthy subjects. Results: A LNSC value above 5.24 ng/ml differentiated CS patients from controls with high sensitivity (96.3%) and specificity (97.1%); we found higher LNSC levels in ectopic CS patients than in CD patients. We found no difference in MSC and LNSC levels between patients with CD in remission and healthy subjects. Both MSC and LNSC levels were higher in patients with adrenal incidentaloma than in healthy controls. A MSC value below 2.65 ng/ml distinguished patients with adrenal insufficiency from controls with high sensitivity (97.1%) and specificity (93.3%). Conclusions: Salivary cortisol is a useful tool to assess endogenous cortisol excess or adrenal insufficiency and to evaluate stable CD in remission.

The diagnostic performance of urinary free cortisol is better than the cortisol:cortisone ratio in detecting de novo Cushing's syndrome: the use of a LC–MS/MS method in routine clinical practice

“…Confirming previously described data regarding LNSC (10,18,19), higher UFF excretion was found in the de novo with respect to the recurrent CD patients, and a higher rate of mild hypercortisolism was found in the latter. We also found normal UFF excretion in two out of ten recurrent CD patients.…”

“…These included: i) Forty-three patients with CS (age at diagnosis 48G18 years). CS suspicion was based on the lack of cortisol suppression !50 nmol/l after 1 mg DST and LNSC levels O5.24 ng/ml (10) in at least two samples. All the subjects had final histological confirmation of CS: 26 had Cushing's disease (CD, 16 de novo and ten recurrences after a minimum of 12 months of remission), 11 with adrenal CS (six adenoma and one carcinoma), and six with ectopic CS (two pancreatic and four bronchial neuroendocrine tumors with positive adrenocorticotropic hormone (ACTH) immunostaining).…”

Age and the metabolic syndrome affect salivary cortisol rhythm: data from a community sample

“…In our volunteers, 4 out of 120 subjects (3%) had late-night salivary cortisol levels that were higher than our local upper cut-off: 11 they were all in the third tertile of age distribution, one was overweight, 2 were obese and 3 were hypertensive. We…”

“…[3][4][5]11,13 We asked unselected subjects living in the community to collect 7 saliva samples on an ordinary weekday in order to define the percentiles of physiological cortisol concentrations at any time-point of the day and the AUC F0àF14 , a mathematical method used to incorporate multiple time-points with an acceptable degree of approximation. 10 Our results confirmed the percentiles of salivary cortisol described elsewhere.…”

“…There were differences in the night salivary cortisol levels in the different age classes: median F 14 levels were higher in the participants in the third tertile of age than those in the second [2. We excluded endogenous Cushing's syndrome in the participants whose late-night salivary cortisol levels were higher than our cut-off (5.24 ng/ml), 11 because Figure 1. Median levels of late-night salivary cortisol (F 14 ) in the participants grouped into age brackets.…”