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Neuroendocrinology and Pituitary

SUN-014 - Short-Term Pharmacodynamic Effects of Osilodrostat Assessed by Serial Salivary Cortisol Monitoring

Sunday, June 14, 2026
9:00 AM - 4:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Masaki Kobatake, MD: No financial relationships to disclose
Masaki Suzuki, M.D., Ph.D.: No financial relationships to disclose


Background:
Osilodrostat is increasingly used for Cushing’s syndrome; however, short-term pharmacodynamics (PD) during early dose titration remain incompletely characterized. Conventional serum or urinary cortisol measurements provide limited information on within-day cortisol dynamics. Serial salivary cortisol sampling may help visualize these PD features and estimate daily cortisol exposure.

Objective:
To characterize short-term PD during osilodrostat titration in patients with Cushing’s syndrome using serial salivary cortisol measurements.

Methods:
This prospective observational study enrolled patients with Cushing’s disease or adrenal Cushing’s syndrome initiating osilodrostat. Osilodrostat was administered twice daily after breakfast and dinner (approximately 08:30–09:00 and 18:30–19:00). Salivary cortisol was sampled at six time points (08:00, 10:00, 12:00, 16:00, 18:00, and 22:00), and 24-hour area under the curve (AUC) was calculated as an index of daily cortisol exposure. Within-day cortisol dynamics were also evaluated using these profiles. This six-point sampling was performed on the initiation or dose-escalation day, again 2–3 days later, and at 1 week. Treatment response was defined as a ≥40% reduction from baseline salivary cortisol AUC. Dose titration was guided by serum/urinary cortisol and clinical status.

Results:
Six patients were included (mean age 50.3 years; all female; Cushing’s disease/adrenal Cushing’s syndrome 4/2). Salivary cortisol AUC showed a strong correlation with same-day urinary free cortisol (UFC) across paired measurements obtained during follow-up (r=0.951, p< 0.001). Five cases (Cases 1–4 and 6) underwent stepwise titration starting at 2 mg/day, while one case (Case 5) with cyclic Cushing’s disease initiated 10 mg/day under a block-and-replace regimen. Among the titrated cases, response was achieved at 2 mg/day in Case 1, 4 mg/day in Case 2, 6 mg/day in Cases 4 and 6, and 8 mg/day in Case 3. In Cases 4 and 6, response was not observed on the day of dose escalation but occurred 4–8 days later, indicating delayed PD effects. In several cases, AUC continued to decline while the same dose was maintained. In Case 5, response was observed 8 days after initiation, with an 85% reduction at Day 14 on the same dose. Case 2 showed continued AUC decline exceeding 80% of baseline at two months, leading to adrenal insufficiency and dose reduction. No abrupt cortisol decline was observed at 1 or 4 hours post-dose.

Conclusion:
Serial salivary cortisol profiling and AUC revealed sustained and gradual PD effects of osilodrostat during early treatment, with continued reduction in daily cortisol exposure even without dose changes. These findings support weekly rather than daily assessment for dose adjustment and may inform future strategies for early titration.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*