Steroids 76 (2011) 38–42 Contents lists available at ScienceDirect Steroids journal homepage: www.elsevier.com/locate/steroids Diagnostic performance of salivary cortisol and serum osteocalcin measurements in patients with overt and subclinical Cushing’s syndrome Márta Sereg a , Judit T ˝ oke a , Attila Patócs a,b , Ibolya Varga b , Péter Igaz a , Nikolette Szücs a , János Horányi c , Péter Pusztai a , Sándor Czirják d , Edit Gláz a , Károly Rácz a , Miklós Tóth a,∗ a 2nd Department of Medicine, Semmelweis University, Szentkirályi u. 46, Budapest H-1088, Hungary b Molecular Medicine Research Group, Hungarian Academy of Sciences and 2nd Department of Medicine, Semmelweis University, Szentkirályi u. 46, Budapest H-1088, Hungary c 1st Department of Surgery, Semmelweis University, Üll ˝ oi út 78, Budapest H-1082, Hungary d National Institute of Neurosurgery, Amerikai út 57, Budapest H-1145, Hungary article info Article history: Received 19 June 2010 Received in revised form 18 August 2010 Accepted 19 August 2010 Keywords: Salivary cortisol Serum osteocalcin Bone markers Cushing’s disease Subclinical Cushing’s syndrome abstract Objective: The cut-off value for salivary cortisol measurement for the diagnosis of Cushing’s syndrome (CS) may depend both on the severity of the disease and the composition of control group. Therefore, we examined the utility of midnight salivary cortisol measurements in patients who were evaluated for signs and symptoms of CS or because they had adrenal incidentalomas. Because serum osteocalcin (OC) is considered as a sensitive marker of hypercortisolism, we also investigated whether OC could have a role in the diagnosis of CS. Patients and methods: Each of the 151 patients was included into one of the following groups: (A) overt CS (n = 23), (B) subclinical CS (n = 18), (C) inactive adrenal adenomas (n = 40), (D) patients without HPA disturbances (n = 70). Patients (C + D) were used as controls. Serum, salivary and urinary cortisol, and OC were measured by electrochemiluminescence immunoassay. Results: Group A had suppressed OC as compared to both group B and group (C + D). Serum and salivary cortisol concentrations showed strong negative correlations with OC in patients with overt CS. The areas under the curves of salivary and serum cortisol at 24:00 h (0.9790 and 0.9940, respectively) serum cor- tisol after low dose dexamethasone test (0.9930) and OC (0.9220) obtained from ROC aanalysis for the diagnosis of overt CS were not statistically different. Conclusion: This study confirms the usefulness of midnight salivary cortisol measurements in the diag- nosis of overt CS in the everyday endocrinological praxis. Our results suggest that OC may have a role in the diagnosis of overt CS. © 2010 Elsevier Inc. All rights reserved. 1. Introduction Many years after the initial reports of salivary cortisol deter- mination [1] midnight salivary cortisol, along with low dose dexamethasone test (LDDST) and urinary free cortisol (UFC) mea- surement [2], has become a first-line laboratory method in the diagnosis of Cushing’s syndrome (CS). However, there are marked differences between different studies in the sensitivity and speci- ficity of salivary cortisol assays [3–7], which may be due to not only differences in clinical settings and the composition of con- trol groups, but they may be also related to differences in the diagnostic performance of various laboratory methods [8] and vari- ations in sample collection techniques [4,11]. Until nowadays, only a few studies reported the diagnostic applicability of an automated ∗ Corresponding author. Tel.: +36 1 4591500; fax: +36 1 2674927. E-mail addresses: totmik@bel2.sote.hu, totmik@gmail.com (M. Tóth). electrochemiluminescence immunoassay for the measurement of salivary cortisol [8,9]. Midnight salivary cortisol may be used with the same thresh- old both in inpatient and outpatient setting [10]. Although several studies have established salivary cortisol reference data in healthy non-obese volunteers [11–13], the use of a control group more closely reflecting the everyday clinical practice (high number of patients with moderate and severe obesity, diabetes mellitus, inci- dentally discovered adrenal masses, etc.) may probably deteriorate the diagnostic performance of salivary cortisol measurements. However, the impact of these disturbing clinical circumstances has not been accurately explored. For example, there is a paucity of reports on the diagnostic utility of salivary cortisol measurements in patients with mild [12] or subclinical CS [14] and in patients with hormonally inactive adrenal tumors [14,15]. Therefore, in the present study we examined midnight salivary cortisol and com- pared its diagnostic utility to other tests including morning salivary cortisol, morning and midnight serum cortisol, LDDST and UFC in a 0039-128X/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.steroids.2010.08.007