Late-Night Salivary Cortisol for Diagnosis of Overt and Subclinical Cushing’s Syndrome in Hospitalized and Ambulatory Patients

Context: Neither precise evaluation of pertinent thresholds nor comparison of the diagnostic performance of late-night salivary cortisol (NSC) between inpatient and outpatient settings has been conducted. The usefulness of NSC for the screening of “subclinical” Cushing’s syndrome is still unknown. Objectives: The aim of the study was to compare the influence of inpatient and outpatient settings on the diagnostic performance of NSC and assess its usefulness as a screening test for subclinical Cushing’s syndrome. Design: Consecutive patients were investigated prospectively with two salivary collections, first as inpatients and then as outpatients. Participants: Forty-two obese subjects participated in the study, as well as nine patients cured of Cushing’s disease, 13 with overt Cushing’s syndrome, 14 showing mild recurrence of Cushing’s disease, and 48 with adrenal incidentalomas [23 subclinical cortisol-secreting adenomas (SCSA), 25 nonsecreting adenomas]. Main Outcome Measures: Reproducibility of NSC and diagnostic performance were measured using receiver operating characteristic analysis. Results: NSC in controls was similar between inpatient and outpatient settings. The diagnostic performance of NSC across the different patient groups was similar irrespective of the setting. A threshold of 12 nmol/liter yielded 100% sensitivity and specificity in overt Cushing’s syndrome. Optimal performance in subclinical Cushing’s syndrome required lower thresholds. NSC showed acceptable performance in diagnosing recurrence of Cushing’s disease (90% sensitivity, 91.8% specificity). On the contrary, NSC was similar between patients with SCSA and nonsecreting adenomas. Conclusions: Our data validate the outpatient bed sampling strategy for NSC with no need for specific outpatient threshold. NSC may be helpful to detect mild recurrence of Cushing’s disease after surgery but is of little value in identifying SCSA amongst adrenal incidentalomas. This study validates outpatient sampling strategy for night salivary cortisol. In subclinical Cushing’s syndrome, night salivary cortisol is helpful to detect recurrence of Cushing’s disease, but not for the evaluation of adrenal incidentalomas.