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

• Published in: European journal of endocrinology Vol. 166; no. 4; pp. 613 - 618
• Main Authors: Deutschbein, Timo, Broecker-Preuss, Martina, Flitsch, Jörg, Jaeger, Andrea, Althoff, Ricarda, Walz, Martin K, Mann, Klaus, Petersenn, Stephan
• Format: Journal Article
• Language: English
• Published: Bristol BioScientifica 01.04.2012
• Subjects: Adrenal Insufficiency - diagnosis; Adrenal Insufficiency - metabolism; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Automation; Biological and medical sciences; Clinical Study; Cushing Syndrome - diagnosis; Cushing Syndrome - metabolism; Diagnostic Techniques, Endocrine - instrumentation; Diagnostic Techniques, Endocrine - standards; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; 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; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reference Values; ROC Curve; Saliva - chemistry; Saliva - metabolism; Sensitivity and Specificity; Vertebrates: endocrinology; Endocrinopathy; Corticosteroid; Adrenal cortex diseases; Steroid hormone; Antiinflammatory agent; Cushing syndrome; Hyperadrenocorticism; Cortisol; Medical screening; Hydrocortisone; Glucocorticoid; Immunological method; Adrenal insufficiency; Adrenal hormone; Adrenal gland diseases; Diagnosis; Saliva; Endocrinology; Tool
• DOI: 10.1530/EJE-11-0945
• ISSN: 0804-4643; 1479-683X

BackgroundSalivary 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).MethodsUnstimulated 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.ResultsWhen 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.ConclusionsThe 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.