ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)
Chronotherapy with once-daily osilodrostat is safe and effective in Cushing’s syndrome and restores circadian profile improving quality of life and sleep
Davide Ferrari 1 , Ilaria Bonaventura 1 , Chiara Simeoli 2 , Alessandra Tomaselli 1 , Ludovica Vincenzi 1 , Dario De Alcubierre 1 , Francesca Sciarra 1 , Flavio Rizzo 1 , Lorenzo Cerroni 1 , Nicola Di Paola 2 , Marianna Minnetti 1 , Emilia Sbardella 1 , Mary Anna Venneri 1 , Riccardo Pofi 3 , Rosario Pivonello 2 , Daniele Gianfrilli 1 , Valeria Hasenmajer 1 & Andrea M Isidori 1,4
1Sapienza University of Rome, Department of Experimental Medicine, Rome, Italy; 2Università Federico II di Napoli, Naples, Italy, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Diabetologia, Andrologia e Nutrizione, Naples, Italy; 3NIHR Oxford Biomedical Research Centre, University of Oxford, Churchill Hospital, Oxford, UK, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK; 4Centre for Rare Diseases (Endo-ERN Accredited), Policlinico Umberto I, Rome, Italy
JOINT1699
Introduction: Medical treatment for Cushing’s syndrome (CS) primarily aims to lower daily cortisol levels, while often overlooking the restoration of circadian rhythm. Indeed, no approved treatment regimens are specifically designed to achieve this goal. We aimed to assess the efficacy and safety of a timed, once-daily Osilodrostat regimen in optimizing circadian cortisol profile in patients with CS.
Methods: We conducted a prospective, multicenter study evaluating patients with well-controlled CS who were on a stable twice-daily Osilodrostat regimen before and 60–90 days after transitioning to an equivalent once-daily dose administered at 19:00±1 hour. Circadian steroid profiles were analyzed in saliva, serum, and urine using UHPLC-MS/MS. A cosinor-based analysis on salivary cortisol and cortisone measurements was performed to capture changes in their daily profiles. Additional evaluations encompassed cardio-metabolic markers, quality of life, sleep function, and safety outcomes.
Results: Sixteen patients (4 males; 7 pituitary, mean age 53.3±11.8 years) were enrolled. At baseline, CS was well-controlled with a mean Osilodrostat dose of 4.2 mg (range 2–22). After the chronotherapy intervention, transitioning to once-daily dosing at 19:00±1 hour, salivary cortisol exposure decreased significantly during the afternoon-to-early morning period [AUC16:00–08:00: −6.1 (−0.15 to −12.1) ng/mL/h, P=.029; AUC16:00–04:00: −4.6 (−1.2 to −8.1) ng/mL/h, P=.009]. Quality of life and sleep improved [CushingQoL: +4.2 (−0.1 to -8.6), P=.029; PSQI: −1.7 (−3.7 to 0.4), P=.049]. Serum steroid precursors, including 11-deoxycorticosterone (AUC08:00–20:00: −3.1 ng/mL/h, P=.008) and 11-deoxycortisol (AUC08:00–20:00: -17.8 ng/mL/h, P=.005), as well as total testosterone in women (AUC0800–2000:=−0.8 ng/mL/h, P=.039), showed a decrease in the global day exposure. A subsequent salivary analysis involved 8 patients that advanced dosing to 16:00±1 hour (TOD2), showing comparable reductions (cortisol AUC16:00–08:00: −5.5 ng/mL/h, P=.036). Once-daily OS was generally well tolerated and preferred by 93.4% of patients to the twice daily regimen in terms of overall appeal, ease of use in daily routine and future choice. No patients developed adrenal insufficiency, liver toxicity, ECG abnormalities, or loss of disease control.
Conclusions: This is the first evidence that chronotherapy with once-daily Osilodrostat effectively and safely treats CS, leading to improvements in circadian cortisol rhythms, quality of life, and sleep. These results warrant further exploration of chronotherapy-based approaches in CS management.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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