A dose-response study of salivary cortisol after dexamethasone suppression test in Cushing's disease and its potential use in the differential diagnosis of Cushing's syndrome

OBJECTIVE A dose-response study with different doses of dexamethasone (dex) to assess the corticotrophic resistance in Cushing's disease (CD) using salivary cortisol as an end point has not yet been evaluated. We also reported our experience with salivary cortisol compared to plasma cortisol determination during dex suppression test (DST) and after ovine corticotrophin release hormone (oCRH) test in the differential diagnosis of Cushing's syndrome (CS). DESIGN We studied 46 patients with CS, including 28 patients with CD, 16 with adrenal disease and two with occult ectopic adrenocorticotropic hormone (ACTH) tumours. Salivary cortisol was compared to plasma cortisol and ACTH during a DST 2 mg for 2 days, 8 mg for 2 days and 24 mg for 1 day, and after oCRH test. RESULTS We observed a dose-dependent suppression of salivary cortisol, plasma cortisol and ACTH in CD patients. Salivary cortisol presented a higher percentage of suppression than plasma cortisol: 42%vs. 15% (P < 0.002), 82%vs. 67% (P < 0.002) and 90%vs. 83% (P < 0.03) after 2, 8 and 24 mg/day dex, respectively. The lowest percentage of suppression was observed for plasma ACTH. The parallelism of these lines identified that the criterion of 65% suppression of salivary cortisol corresponding to 50% suppression of plasma cortisol after 8 mg/day for 2 days is consistent with CD. The sensitivity and specificity using 50% suppression for plasma cortisol were 81% and 83%, respectively, for 8 mg DST. Using the criterion of 65% suppression of salivary cortisol, the sensitivity and specificity were 86% and 100%, respectively, for 8 mg DST. After oCRH test the sensitivity and specificity were 86% and 91%, respectively, for ACTH, 100% and 64%, respectively, for plasma cortisol and 93% and 91%, respectively, (20% of increment) or 86% and 100%, respectively, (35% increment) for salivary cortisol. CONCLUSION In conclusion, salivary cortisol presents more profound suppression than plasma cortisol or ACTH in a dose-response pattern after different doses of dex in patients with CD. In addition, our data suggest that measurement of salivary cortisol might improve the DST as compared to plasma cortisol in the differential diagnosis of CS.