The Journal of clinical endocrinology and metabolism · 2026
Osilodrostat-associated Adrenal Gland Shrinkage: A Case Series of Patients With ACTH-dependent Cushing's Syndrome.
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Varlamov Elena V, Park Brian J, Fleseriu Maria
Аннотация
CONTEXT: Medical therapy for Cushing's syndrome (CS) is increasingly used. A potent adrenal steroidogenesis inhibitor, osilodrostat, has been rarely linked to prolonged adrenal insufficiency (AI).
OBJECTIVE: We hypothesized that osilodrostat-induced AI could be associated with adrenal gland shrinkage.
DESIGN: Noninterventional, retrospective, longitudinal, institutional review board-approved study of patients with CS treated at Oregon Health and Science University between January 1, 2000, and July 1, 2025.
SETTING: Ambulatory and inpatient, academic, quaternary medical center.
PATIENTS OR OTHER PARTICIPANTS: Patients with ACTH-dependent CS, treated with osilodrostat for >3 months, and computed tomography (CT) imaging before and after osilodrostat available for adrenal volume (AV) measurement.
INTERVENTION(S): Age, sex, osilodrostat doses and duration, laboratory data, and AI were recorded. AV was calculated using manual segmentation on CT images by a board-certified radiologist.
MAIN OUTCOME MEASURE(S): AV before and after initiation of osilodrostat was expressed as percent reduction.
RESULTS: Ten patients (5 ectopic CS, 4 unknown ACTH source, 1 Cushing's disease) were included. Osilodrostat mean starting, maximum, and final doses: 7.7, 13.8, and 5.9 mg/day, respectively, over 23 months. Four patients received block-and-replace regimen, AI developed in 5. Adrenal gland volume decreased by 46.7 ± 22.2% from 25.5 ± 9.9 mL to 12.7 ± 6.4 mL, P < .001 over a median of 19 months. AV reduction positively correlated with maximum osilodrostat dose, r = 0.626, P = .027.
CONCLUSION: We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients.
OBJECTIVE: We hypothesized that osilodrostat-induced AI could be associated with adrenal gland shrinkage.
DESIGN: Noninterventional, retrospective, longitudinal, institutional review board-approved study of patients with CS treated at Oregon Health and Science University between January 1, 2000, and July 1, 2025.
SETTING: Ambulatory and inpatient, academic, quaternary medical center.
PATIENTS OR OTHER PARTICIPANTS: Patients with ACTH-dependent CS, treated with osilodrostat for >3 months, and computed tomography (CT) imaging before and after osilodrostat available for adrenal volume (AV) measurement.
INTERVENTION(S): Age, sex, osilodrostat doses and duration, laboratory data, and AI were recorded. AV was calculated using manual segmentation on CT images by a board-certified radiologist.
MAIN OUTCOME MEASURE(S): AV before and after initiation of osilodrostat was expressed as percent reduction.
RESULTS: Ten patients (5 ectopic CS, 4 unknown ACTH source, 1 Cushing's disease) were included. Osilodrostat mean starting, maximum, and final doses: 7.7, 13.8, and 5.9 mg/day, respectively, over 23 months. Four patients received block-and-replace regimen, AI developed in 5. Adrenal gland volume decreased by 46.7 ± 22.2% from 25.5 ± 9.9 mL to 12.7 ± 6.4 mL, P < .001 over a median of 19 months. AV reduction positively correlated with maximum osilodrostat dose, r = 0.626, P = .027.
CONCLUSION: We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients.