Chronotherapy With Once-Daily Osilodrostat Improves Cortisol Rhythm, Quality of Life, and Sleep in Cushing's Syndrome
Authors' conclusion
Once-daily osilodrostat effectively and safely treats patients with biochemically controlled CS, improving circadian cortisol profiles, quality of life, and sleep. Findings support further exploration of chronotherapy-based approaches in CS management.
Study context
- Population
- Patients with well-controlled Cushing syndrome (CS) on stable twice-daily osilodrostat; 4 males, 7 pituitary, mean age 53.3 ± 11.8 years
- Participants
- 16 patients
- Exposure
- Once-daily osilodrostat at 19:00 ± 1 hour vs prior twice-daily osilodrostat
- Outcome
- Salivary cortisol exposure, afternoon to early morning (AUC16:00-08:00), change after transitioning to once-daily dosing
- Follow-up
- 60 to 90 days after transitioning
Methodological detailsmulticenter
- Multicenter
Main finding
As reported in the abstract
Salivary cortisol AUC16:00-08:00 decreased significantly after transitioning (ng/mL/h; P = .029)
−6.1
−0.15 to −12.1
Observational data: associations, not effects.
Further findings
Quality of life (CushingQoL)
- CushingQoL improved after transitioning (P = .029)
- +4.2
Sleep (Pittsburgh Sleep Quality Index)
- Pittsburgh Sleep Quality Index improved after transitioning (P = .049)
- −1.7
Serum 11-deoxycorticosterone
- 11-deoxycorticosterone decreased after transitioning (ng/mL/h; P = .008)
- −3.1
Serum 11-deoxycortisol
- 11-deoxycortisol decreased after transitioning (ng/mL/h; P = .005)
- −17.8
Dosing advanced to 16:00 ± 1 hour (subgroup)
- Comparable reductions, with phase shifts in acrophase and nadir
- 8 patients
Safety
- Adrenal insufficiency, liver toxicity, ECG abnormalities or loss of disease control
- 0
Original publication
Chronotherapy With Once-Daily Osilodrostat Improves Cortisol Rhythm, Quality of Life, and Sleep in Cushing's Syndrome. J Clin Endocrinol Metab. Published 2 April 2025. doi:10.
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