Endocrine Abstracts

Adrenal insufficiency (AI) is associated with morbidity and premature mortality. The short Synacthen test (SST) is the reference diagnostic test for AI but requires repeated intravenous clinic-based sampling. Recently, waking salivary cortisone has been proposed as a convenient non-invasive alternative for initial screening. We sought to validate this approach and further define clinically useful cut-off values for morning salivary cortisone. We retrospectively analysed a real-world cohort of 543 patients who underwent an SST for suspected AI, with paired serum cortisol (SerF), salivary cortisol (SalF) and salivary cortisone (SalE) measurements. All patients attended our centre, a tertiary endocrine referral centre in Manchester. SerF was measured using immunoassay and salivary glucocorticoids using liquid-chromatography tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to determine sensitivity and specificity. Thresholds to exclude adrenal insufficiency were derived at ~97% and 100% sensitivity for baseline serF, salF and salE. Decision curve analysis (DCA) was then used to assess net clinical benefit at these thresholds. At baseline measurement, salivary cortisone achieved an area under the curve (AUC) of 0.93 (95% CI 0.91-0.95). This was comparable with baseline/morning serum cortisol (AUC 0.93, 95% CI 0.90-0.95) and significantly superior to baseline/morning salivary cortisol (AUC 0.87, 95% CI 0.83-0.91) for predicting SST outcome (DeLong: Z=3.419; P = 0.00063). A salivary cortisone threshold of 19.9 nmol/l excluded adrenal insufficiency with 97% sensitivity and 59% specificity (LR- 0.05), while 21.2 nmol/l achieved 100% sensitivity and 52% specificity (LR- 0.00). DCA showed that a baseline/morning salivary cortisone threshold of 19.9 nmol/l provided the greatest net clinical benefit across relevant probability thresholds and was comparable to the NICE guideline morning cortisol cut-off of >300 nmol/l. Our threshold value is consistent with previous studies, lending support to adopting salivary cortisone as a first-line screening test for adrenal insufficiency.