Safety management in Cushing syndrome during osilodrostat treatment based on morning blood cortisol level

Osilodrostat dosage is adjusted based on 24-h urinary free cortisol (UFC) levels. However, approximately 1 week is required to obtain the results. In contrast, serum cortisol levels are available soon after sampling, allowing the determination of osilodrostat doses promptly. However, this issue remains poorly understood. Therefore, this study aimed to determine whether a simultaneous assay of serum cortisol and UFC concentrations is useful in patients with Cushing syndrome (CS) receiving osilodrostat. This was a retrospective cross-sectional study. A total of 71 paired samples in six patients with CS during osilodrostat treatment were analyzed in this study. The 24-h urine sample collection was started from the day before blood sampling, and UFC and morning serum cortisol levels were measured on the same day. Commercially available immunoassay kits were used for the hormone measurements. A significant positive correlation between morning cortisol levels and UFC levels was observed. Receiver operating characteristic analysis showed a cut-off of 21.5 μg/dL for serum cortisol as the best indicator to predict high UFC levels. The cut-off secured UFC samples >3× the upper limit of normal. However, the positive predictive value of serum cortisol levels in predicting low UFC was considerably low. A serum cortisol level <5.0 μg/dL, which is often used to suggest adrenal insufficiency, captured patients with hypocortisolism even when the serum cortisol and UFC results were discordant. Simultaneous measurements of single morning serum cortisol and UFC levels on the same day will promote safety in patients with CS who are being treated with osilodrostat.