The diagnostic accuracy of increased late night salivary cortisol for Cushing’s syndrome: a real-life prospective study

  • F. CeccatoEmail author
  • G. Marcelli
  • M. Martino
  • C. Concettoni
  • M. Brugia
  • L. Trementino
  • G. Michetti
  • G. Arnaldi
Original Article


Introduction and aim

A prompt diagnosis of Cushing’s Syndrome (CS) in high-risk populations is mandatory: 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), and urinary-free cortisol (UFC) are recommended, despite thresholds calculated in retrospective studies. Our aim was to study the diagnostic accuracy of LNSC measured with chemiluminescence assay in a prospective study, confirming discrepancies with mass spectrometry (MS).

Materials and methods

We enrolled 117 controls and 164 suspected CS (CS = 47, non-CS = 117). In case of increased LNSC, high clinical suspicion of CS or adrenal incidentaloma, patients were hospitalized to exclude/confirm CS.


LNSC levels were higher in patients with suspected CS, CS, and non-CS than controls. Considering 16 nmol/L as threshold for CS, overall LNSC revealed SE 97% and SP 84% in the whole group of subjects considered, achieving positive/negative likelihood ratio of 5.56/0.045, respectively. 35 out of 81 subjects with increased LNSC were non-CS (15 diabetic and 20 obese): considering only those patients with increased likelihood to have a CS (the non-CS patients) SP decreased to 70%, and further reduced to 60% if we discharged subjects with adrenal incidentaloma. MS analyses reduced partially the number of false-positive LNSC.


LNSC measured in automated chemiluminescence is reliable in clinical practice: it present a high diagnostic accuracy to exclude hypercortisolism in patients with normal cortisol levels. MS could be used to reduce the number of false-positive results; nevertheless, some non-CS subjects with functional hypercortisolism could have a mild impairment of cortisol rhythm.


Cushing’s syndrome Late night salivary cortisol Diagnosis Liquid chromatography–tandem mass spectrometry 



Authors are grateful to prof. Carla Scaroni for the critical review of the manuscript.


This study did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflicts of interest that might be perceived as influencing the impartiality of the reported research.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Italian Society of Endocrinology (SIE) 2018

Authors and Affiliations

  1. 1.Endocrinology Unit, Department of Medicine DIMEDUniversity-Hospital of PadovaPaduaItaly
  2. 2.Division of Endocrinology, Department of Clinical and Molecular Sciences (DISCLIMO), Umberto I HospitalPolytechnic University of MarcheTorretteItaly

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