EYES2023 ESE Young Endocrinologists and Scientists (EYES) 2023 Oral communication 2: Neuroendocrinology (6 abstracts)
Comparison of metyrapone, osilodrostat and ketoconazole in the short-term therapy of endogenous Cushing’s syndrome: Preliminary results of the Mosketeer study
Mario Detomas 1 , Chiara Simeoli 2 , Nicola Di Paola 2 , Alessandro Mazzarella 2 , Rosario Pivonello 2 , Filippo Ceccato 3 , Giacomo Voltan 3 , Carla Scaroni 3 , Anna Aulinas , Alicia Santos 4 , Susan Webb 4 , German Rubinstein 5 , Leah Braun 5 , Martin Reincke 5 , Pasquale Dolce 6 , Simone Antonini 7 , Andrea Lania 7 , Maria Stelmachowska-Banaś 7 , Karolina Cylke-Falkowska 8 , Marianna Minnetti 9 , Andrea M. Isidori 9 , Andrea Corsello 10 , Aleksandra Gilis-Januszewska 11 , Mari Minasyjan 11 , Lana Sambula 12 , Darko Kastelan 12 , Timo Deutschbein 13 , Linus Haberbosch 14 , Ulrich Dischinger 15 , Martin Fassnacht 15 & Barbara Altieri 15
1University Hospital Würzburg; Medizinische Klinik I; Division of Endocrinology and Diabetes, Würzburg, Germany, Department of Internal Medicine I, Division of Endocrinology and Diabetes, Würzburg, Germany; 2Dipartimento DI Medicina Clinica e Chirurgia, Sezione DI Endocrinologia, Università Federico II DI Napoli, Naples, Italy; 3Endocrine Disease Unit, University-Hospital of Padova, Padova, Italy; 4Department of Endocrinology, Hospital S Pau, Barcelona; Iib-Sant Pau, Research Center for Pituitary Diseases, Barcelona; Ciberer Unit 747, Isciii and Department of Medicine, Univ Autonoma Barcelona, Spain; 5Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich 80336, Germany; 6Department of Public Health, University of Naples Federico II, Naples, Italy.; 7Endocrinology, Diabetology and Medical Andrology Unit, Irccs Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy; 8Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland; 9Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy; 10Department of Translational Medicine and Surgery, Unit of Endocrinology, Università Cattolica del Sacro Cuore-Fondazione Policlinico Universitario A. Gemelli Irccs, Largo Gemelli 8, I-00168 Rome, Italy; 11Jagiellonian University Medical College, Department of Endocrinology, Krakow, Poland; 12University Hospital of Zagreb, Department of Endocrinology, Croatia; 13Medicover Oldenburg Mvz, Oldenburg, Germany; 14University Hospital of Berlin (Charite); 15Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Würzburg, Germany.
Background: Steroid synthesis inhibitors, like metyrapone, osilodrostat, and ketoconazole are used as second-line treatment in all types of endogenous Cushing’s syndrome (CS). However, a direct comparison of these three drugs is missing. This study aimed to compare these drugs in the short-term therapy of CS.
Design: Retrospective multicenter study involving 16 centers worldwide.
Methods: Patients with CS treated with metyrapone, osilodrostat or ketoconazole as monotherapy for at least 2 weeks were considered eligible. Main outcomes were changes in 24h urinary free cortisol (24h-UFC) after 2(T1), 4(T2), and 12 weeks(T3) of therapy compared to baseline (T0), evaluated as delta (change) percentage from T0.
Results: Data of 328 patients from 13/16 centers were available. 128(39%) patients were treated with metyrapone, 91(28%) with osilodrostat and 109(33%) with ketoconazole. No difference in terms of CS subtypes (P=0.6) and baseline 24h-UFC (median 307μg/24 h, 253 μg/24 h and 294 μg/24 h for metyrapone, osilodrostat and ketoconazole, respectively, P=0.5) was identified. Median daily starting doses were 750 (range 250–1000) mg, 4 (1–10) mg and 400 (200–800) mg for metyrapone, osilodrostat and ketoconazole, which increased at T3 for all drugs. Considering the patients with a lower dose (according to the median of each drug), 24 h-UFC decreased at T1 in all treatments (−25% metyrapone, −19% osilodrostat, −22% ketoconazole, P=0.21). If patients with higher doses were considered, a more pronounced decrease in 24h-UFC in osilodrostat compared to metyrapone was observed at T1 (−46% vs −22%, P<0.05). At T3 20(16%) patients under metyrapone, 8(9%) under osilodrostat and 4 under ketoconazole (4%) were supplemented with potassium(P<0.0001). At T1, a decrease in number of antihypertensives was identified in 7%of patients under metyrapone, 17%under osilodrostat and 7%under ketoconazole (P<0.001).
Conclusion: These preliminary results confirmed the efficacy of all the three drugs in decreasing hypercortisolism. Osilodrostat might act faster in decreasing blood pressure. However, these preliminary results need to be validated in the final cohort.
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Endocrine Abstracts
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