Salivary cortisol as a diagnostic tool for Cushing's syndrome and adrenal insufficiency: improved screening by an automatic immunoassay.
BACKGROUND
Salivary cortisol is increasingly used to assess patients with suspected hypo- and hypercortisolism. This study established disease-specific reference ranges for an automated electrochemiluminescence immunoassay (ECLIA).


METHODS
Unstimulated saliva from 62 patients with hypothalamic-pituitary disease was collected at 0800 h. A peak serum cortisol level below 500 nmol/l during the insulin tolerance test (ITT) was used to identify hypocortisolism. Receiver-operating characteristic (ROC) analysis allowed establishment of lower and upper cutoffs with at least 95% specificity for adrenal insufficiency and adrenal sufficiency. Saliva from 40 patients with confirmed hypercortisolism, 45 patients with various adrenal masses, and 115 healthy subjects was sampled at 2300 h and after low-dose dexamethasone suppression at 0800 h . ROC analysis was used to calculate thresholds with at least 95% sensitivity for hypercortisolism. Salivary cortisol was measured with an automated ECLIA.


RESULTS
When screening for secondary adrenal insufficiency, a lower cutoff of 3.2 nmol/l and an upper cutoff of 13.2 nmol/l for unstimulated salivary cortisol allowed a highly specific diagnosis (i.e. similar to the ITT result) in 26% of patients. For identification of hypercortisolism, cutoffs of 6.1 nmol/l (sensitivity 95%, specificity 91%, area under the curve (AUC) 0.97) and 2.0 nmol/l (sensitivity 97%, specificity 86%, AUC 0.97) were established for salivary cortisol at 2300 h and for dexamethasone-suppressed salivary cortisol at 0800 h.


CONCLUSIONS
The newly established thresholds facilitated initial screening for secondary adrenal insufficiency and allowed excellent identification of hypercortisolism. Measurement by an automated immunoassay will allow broader use of salivary cortisol as a diagnostic tool.
Department of Endocrinology and Division of Laboratory Research, Medical Center, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen, Germany.
Timo
T
Deutschbein
Martina
M
Broecker-Preuss
Jörg
J
Flitsch
Andrea
A
Jaeger
Ricarda
R
Althoff
Martin K
MK
Walz
Klaus
K
Mann
Stephan
S
Petersenn
D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D001331:Automation; D003480:Cushing Syndrome / Q000175:diagnosis* / Q000378:metabolism; D003940:Diagnostic Techniques, Endocrine / Q000295:instrumentation / Q000592:standards; D005260:Female; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis* / Q000378:metabolism; D007118:Immunoassay / Q000295:instrumentation / Q000379:methods / Q000592:standards; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012016:Reference Values; D012463:Saliva / Q000737:chemistry* / Q000378:metabolism; D012680:Sensitivity and Specificity
D006854:Hydrocortisone