Neoplastic hypercortisolism: Cut-off values for late-night salivary cortisol & cortisone

One of the recommended initial tests for diagnosing neoplastic hypercortisolism is the measurement of late-night salivary cortisol (Cortisol_LNSa). Published cut-off values for Cortisol_LNSa and late-night salivary cortisone (Cortisone_LNSa) vary widely between studies. This study aims to establish cut-off values for Cortisol_LNSa and Cortisone_LNSa using liquid chromatography-tandem mass spectrometry and to determine which salivary hormone performs better in distinguishing between people with and without neoplastic hypercortisolism.

A retrospective study was conducted on subjects screened for endogenous hypercortisolism at Amsterdam UMC between December 2015 and February 2022. 25 subjects with and 430 subjects without neoplastic hypercortisolism were included. The diagnosis neoplastic hypercortisolism was confirmed by histology and postoperative clinical features, not on biochemical tests, and excluded based on a follow-up of at least 12 months without progressive clinical signs of neoplastic hypercortisolism. Salivary samples were collected between 22:00-23:59 h and Cortisol_LNSa and Cortisone_LNSa concentrations were measured using liquid chromatography-tandem mass spectrometry.

The median Cortisol_LNSa was 7.8 nmol/L for subjects with and 0.8 nmol/L for subjects without neoplastic hypercortisolism (p < 0.001). The median Cortisone_LNSa was 35.5 nmol/L and 5.3 nmol/L, respectively (p < 0.001). Optimal diagnostic accuracy was established at 2.25 nmol/L for Cortisol_LNSa (sensitivity 92 %, specificity 89 %, positive predictive value 32.9 %, negative predictive value 99.5 %) and 15.5 nmol/L for Cortisone_LNSa (sensitivity 93.8 %, specificity 94.5 %, positive predictive value 46.9 %, negative predictive value 99.7 %).

We established cut-off values for Cortisol_LNSa and Cortisone_LNSa for the diagnosis of neoplastic hypercortisolism. Cortisone_LNSa provided the highest diagnostic accuracy and we therefore recommend it as the preferred salivary measurement.