Salivary cortisol as a diagnostic tool for Cushing's syndrome and adrenal insufficiency: improved screening by an automatic immunoassay

Eur J Endocrinol. 2012 Apr;166(4):613-8. doi: 10.1530/EJE-11-0945. Epub 2012 Jan 3.

Abstract

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.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Adrenal Insufficiency / diagnosis*
  • Adrenal Insufficiency / metabolism
  • Adult
  • Automation
  • Cushing Syndrome / diagnosis*
  • Cushing Syndrome / metabolism
  • Diagnostic Techniques, Endocrine* / instrumentation
  • Diagnostic Techniques, Endocrine* / standards
  • Female
  • High-Throughput Screening Assays / instrumentation
  • High-Throughput Screening Assays / methods*
  • High-Throughput Screening Assays / standards
  • Humans
  • Hydrocortisone / analysis*
  • Hydrocortisone / metabolism
  • Immunoassay / instrumentation
  • Immunoassay / methods
  • Immunoassay / standards
  • Male
  • Middle Aged
  • ROC Curve
  • Reference Values
  • Saliva / chemistry*
  • Saliva / metabolism
  • Sensitivity and Specificity

Substances

  • Hydrocortisone