Saliva versus serum cortisol to identify subclinical hypercortisolism in adrenal incidentalomas: simplicity versus accuracy

Abstract

Subclinical hypercortisolism (SCH) leads to metabolic derangements and increased cardiovascular risk. Cortisol autonomy is defined by the overnight 1mg dexamethasone suppression test (DST). Saliva cortisol is an easier, stress-free, and cost-effective alternative to serum cortisol. We compared 23h and post-1mg DST saliva with serum cortisol to identify SCH in adrenal incidentalomas (AI). We analyzed 359 DST obtained retrospectively from 226 AI subjects (173F/53M; 19-83years) for saliva and serum cortisol. We used three post-DST serum cortisol cutoffs to uncover SCH: 1.8, 2.5, and 5.0μg/dL. We determined post-DST and 23h saliva cortisol cutoffs by ROC curve analysis and calculated their sensitivities (S) and specificities (E). The sensitive 1.8μg/dL cutoff defined 137 SCH and 180 non-functioning adenomas (NFA): post-DST and 23h saliva cortisol S/E were: 75.2%/74.4% and 59.5%/65.9%, respectively. Using the specific 5.0μg/dL cortisol cutoff (22 SCH/295 NFA), post-DST and 23h saliva cortisol S/E were 86.4%/83.4% and 66.7%/80.4%, respectively. Using the intermediate 2.5μg/dL cutoff (89 SCH/228 NFA), post-DST and 23h saliva cortisol S/E were 80.9%/68.9% and 65.5%/62.8%, respectively. Saliva cortisol showed acceptable performance only with the 5.0μg/dL cortisol cutoff, as in overt Cushing's syndrome. Lower cutoffs (1.8 and 2.5μg/dL) that identify larger samples of patients with poor metabolic outcomes are less accurate for screening. These results may be attributed to pre-analytical factors and inherent patient conditions. Thus, saliva cortisol cannot replace serum cortisol to identify SCH among patients with AI for screening DST.