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

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 dexamethasonesuppressed 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.

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

“…As reported in some studies (2,5,6,7,10,11,12,14), we found that LNSC levels were higher in CS; a threshold value above 5.24 ng/ml provided a good accuracy to detect endogenous hypercortisolism, and in particular to discover CD, the most common form. LNSC was able to differentiate CS patients from the control population, which included not only healthy subjects but also patients with suspected CS, and our proposed threshold value is consistent with other data reported in the literature and obtained with RIAs (5, 11, 23).…”

“…Salivary cortisol is increasingly being used to assess hyper-or hypocortisolism (1,2). The measurement of late-night salivary cortisol (LNSC) levels in combination with the 1 mg dexamethasone suppression test (DST) and that of urinary free cortisol (UFC) levels have been proposed as the first-line laboratory tests in the diagnosis of Cushing's syndrome (CS) (3).…”

“…The lack of a circadian rhythm is a peculiar marker of CS (4), so the LNSC test seems to be the best choice to screen for CS because of its noninvasive, stress-free, easy collection in outpatients (1). There is a marked variation between studies in the performance of the LNSC test, reflecting differences in laboratory assays, sample collection, severity of CS, and control groups (2,5,6,7,8,9,10,11,12,13,14). It is also important to have reference data not only for healthy volunteers but also for a control group of obese, hypertensive, diabetic, and depressed subjects or other clinical features of CS that are common in the general population (3,15).…”

“…Healthy people show physiologically high levels of salivary cortisol when they wake up, and some authors have reported that low salivary cortisol levels may thus be a marker of adrenal insufficiency (2,6,19). None of these studies have looked for differences between primary and secondary adrenal insufficiency; in the latter, some residual HPA axis activity may be confounding.…”

Assessment of glucocorticoid therapy with salivary cortisol in secondary adrenal insufficiency

“…Salivary steroids are a non-invasive, easily repeated, stress-free way to measure circulating free hormone levels (12,13), recently recommended for assessing cortisol profiles in healthy people (14,15) and in patients with hypothalamic-pituitary-adrenal (HPA) axis disorders (16,17).…”