The role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism (SH) in patients with adrenal incidentaloma

Background: Several criteria (i.e., cortisol supprimibility after 1 mg overnight dexamethasone suppression test -F-dex-, low ACTH levels, high 24 h urinary free cortisol levels -UFC-, high midnight serum cortisol levels) have been used for defining SH. Nevertheless, a real gold standard combination of tests is lacking. Recently midnight salivary cortisol (MSC) has been described as a sensitive marker for the diagnosis of overt hypercortisolism, while the role of MSC in the diagnosis of SH is not known. We evaluated the role of midnight salivary cortisol levels in diagnosing SH in AI subjects. Subjects and methods: In 62 (F/M 38/24) patients with AI and in 45 (F/M 26/19) healthy controls matched for age, MSC levels were evaluated. In AI patients the evaluation of F-dex, UFC and ACTH plasma levels was also performed. We defined as affected with SH patients showing 2 out of the following: F-dex >83.0 nmol/l, ACTH <2.2 pmol/l, UFC >284 nmol/l. On the basis of these criteria, 12 patients showed SH (SH+) and 50 did not (SH−). The normal values of MSC are 0.7—5.7 nmol/l. The upper limit corresponds to the 95th percentile value of 45 controls. Data are expressed as mean±S.D. Results: Age, BMI and percentage of males and females were comparable between SH+ and SH− patients. MSC levels were higher in patients with SH (4.6±2.3 nmol/l) than in patients without SH (2.2±3.1 nmol/l, P=0.006) and controls (1.7±1.8 nmol/l, P=0.001). The MSC levels showed a significant correlation with F-dex (r=0.28, P<0.05). Using the cut-off of 5.7 nmol/l the sensitivity and the specificity of MSC levels for diagnosing SH is 33% and 90% respectively. In patients with AI normal levels of MSC do not exclude hypercortisolism whereas high levels can confirm the presence of SH suggested by conventional endocrine tests.