Salivary Cortisol and Cortisone After Low-Dose Corticotropin Stimulation in the Diagnosis of Adrenal Insufficiency

CONTEXT: Basal and poststimulation salivary cortisol and cortisone levels can be useful in the diagnosis of adrenal insufficiency. However, little is known about the optimal cutoffs and performance characteristics of these tests. OBJECTIVE: To derive the cutoff values and study the performance characteristics of salivary cortisol and salivary cortisone in the diagnosis of adrenal insufficiency. DESIGN AND SETTING: Prospective study in a regional hospital in Hong Kong from January 2014 to September 2015. PARTICIPANTS: Fifty-six Chinese healthy volunteers and 171 patients suspected of having adrenal insufficiency. MAIN OUTCOME MEASURES: All participants underwent low-dose short Synacthen test (LDSST) with intravenous injection of 1 μg of tetracosactide (Synacthen 1–24). Serum cortisol, salivary cortisol and cortisone levels were measured at baseline and 30 and 60 minutes afterward. RESULTS: Using the reference cutoff (mean − 2 standard deviations of post-LDSST peak serum cortisol) derived from healthy volunteers as the gold standard, receiver operating characteristic analysis of patients’ data revealed that both post-LDSST peak salivary cortisol and cortisone performed better than basal tests. The most optimal cutoff values for serum cortisol as measured by immunoassay and for salivary cortisol and salivary cortisone as measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) were 376, 8.6, and 33.5 nmol/L, respectively, for post-LDSST peak values, and 170, 1.7, and 12.5 nmol/L, respectively, for basal values. CONCLUSIONS: We established method-specific reference cutoffs for serum cortisol, salivary cortisol, and salivary cortisone during LDSST. Both post-LDSST peak salivary cortisol and cortisone performed well as diagnostic tests for adrenal insufficiency. Their measurements by LC-MS/MS can alleviate problems associated with serum cortisol immunoassays.