Endocrine Abstracts

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 recommend, 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 (final CS=47, non-CS=117). In case of increased LNSC, high clinical suspicion of CS or adrenal incidentaloma, patients were hospitalized in order to exclude/confirm CS.

Results: We found a large number of false positive results: 35 out of 81 subjects with increased LNSC were non-CS (15 diabetic and 20 obese patients). 2 out of 29 patients with adrenal incidentaloma presented an impaired serum cortisol rhythm. Considering 16 nmol/L as threshold for CS diagnosis, overall LNSC revealed sensitivity (SE) of 97% (95% CI 0.817–0.993) and specificity (SP) of 84% (95% CI 0.772–0.871) in the whole group of subjects considered. If we considered the group of non-CS (those patients with increased likelihood to have a CS), the number of false positive results increased, and therefore the SP decreased to 70% (95% CI 59.8–76.3). SP dropped to 60% (95% CI 49–68.3) if we discharged patients with adrenal incidentaloma. Therefore, we re-computed the threshold of LNSC only in the group of CS compared to non-CS: increasing the cut-off (21.9 nmol/l) we gained in SP (77%) and lost in SE (92%). We measured cortisol with MS in those patients with increased LNSC results in chemiluminescence or high clinical suspicion of CS. MS confirmed the false negative LNSC result of the one patient with confirmed CS and normal cortisol rhythm with chemiluminescence (respectively 1 and 0.6 nmol/l). Considering the 35 non-CS subjects with false positive increased LNSC in chemiluminescence, in half cases MS analyses revealed a normal LNSC.

Conclusions: 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.