Daily salivary cortisol and cortisone rhythm in patients with adrenal incidentaloma

Impaired cortisol rhythm is a characteristic feature of Cushing's Syndrome, nevertheless late night salivary cortisol (LNSC) is not suitable to detect subclinical hypercortisolism in patients with adrenal incidentaloma (AI). We studied daily salivary cortisol (F) and cortisone (E) rhythm in patients with AI. Six saliva samples were collected from awakening to night in 106 patients with AI and 40 controls. F and E were measured with LC-MS/MS and daily F exposure was calculated with the area under the curve (AUC). Patients with serum cortisol after dexamethasone suppression test (DST) > 50 nmol/L showed higher morning F (15.5 +/- 14.5 vs. 8.6 +/- 5.5 nmol/L, p = 0.001), suppressed corticotropin levels (76 vs. 35%, p < 0.001) and increased daily F exposure (3795 +/- 1716 vs. 2898 +/- 1478, p = 0.012), especially in the morning (2035 +/- 1267 vs. 1365 +/- 777, p = 0.003), otherwise LNSC levels were similar. Salivary E and AUC levels were higher in patients with DST > 50 nmol/L. AUC was not correlated with urinary cortisol levels or adenoma size. F and E levels were similar among patients with unilateral or bilateral adenoma, or considering the presence of hypertension, dyslipidemia, diabetes, or cardiovascular events. Daily cortisol exposure, evaluated with AUC from multiple saliva collections, is increased in AI patients with serum cortisol > 50 nmol/L after DST, especially in the morning, leading to reduced corticotropin levels. Cortisol rhythm is preserved in patients with AI, remarking that LNSC is not a screening test for subclinical hypercortisolism.