Osilodrostat use in severe pediatric cushing

Alessandro Barbato; Medico Giulia Del; Gaia Varriale; Alessio Rossi; Laura Corbelli; Luca Manetti; Carlo Urbani; Giovanna Cristella; Mirko Scagnet; Nicolo Chiti; Stefano Stagi

doi:10.1530/endoabs.110.EP1089

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Endocrine Abstracts (2025) 110 EP1089 | DOI: 10.1530/endoabs.110.EP1089

ECEESPE2025 ePoster Presentations Pituitary, Neuroendocrinology and Puberty (220 abstracts)

Osilodrostat use in severe pediatric cushing’s syndrome: short term outcomes in a case of pituitary adenoma

Alessandro Barbato ^1,2 , Giulia Del Medico ^1,2 , Gaia Varriale ² , Alessio Rossi ^1,2 , Laura Corbelli ^1,2 , Luca Manetti ³ , Carlo Urbani ³ , Giovanna Cristella ⁴ , Mirko Scagnet ⁵ , Nicolò Chiti ² & Stefano Stagi ^1,2

Author affiliations

¹University of Florence, Department of Health Sciences, Florence, Italy; ²Meyer Children’s Hospital IRCCS, Auxo-endocrinology Unit, Florence, Italy; ³University of Pisa, Department of Clinical and Experimental Medicine, Section of Endocrinology, Pisa, Italy; ⁴IRCCS Don Carlo Gnocchi Foundation, Florence, Italy; ⁵Meyer Children’s Hospital IRCCS, Pediatric Neurosurgery, Florence, Italy

JOINT1724

Background: Osilodrostat is an inhibitor of steroidogenesis approved for treatment of Cushing’s disease in adults. It acts against 11β-hydroxylase (CYP11B1) which catalyzes the last step in cortisol synthesis. A trial in the pediatric population is ongoing to assess its pharmacodynamics, pharmacokinetics and tolerability (NCT03708900) but data about its efficacy in pediatric Cushing’s disease are lacking.

Case presentation: A 10-years-9months old boy was transferred to the Intensive care Unit (ICU) of our center for refractory hypokalemia and sinus bradycardia with U waves. Upon clinical examination he presented facies lunaris, acne, central obesity and striae rubrae. Laboratory tests showed ACTH 139.7ng/l, serum cortisol 118 μg/dl (2.4-15), urinary free cortisol (UFC) 45 585.2 nmol/24h (upper reference range, URR, 124) at the first 24 h urine collection and 21 877.5 on the second collection. Considering UFC, Brain MRI was performed and revealed a hypophyseal mass: diagnosis of Cushing’s disease was confirmed. Surgery to remove the hypophyseal adenoma was performed but it was complicated by meningitis requiring antibiotic therapy and a further period of recovery in ICU. Despite initial reduction, both ACTH and cortisol progressively increased up to 969 ng/lfor the former and 149 μg/dl for the latter, within three weeks after surgery. After 24 hours of treatment with Metyrapone, Osilodrostat was started at a dose of 1 mg twice daily. Due to swallowing issues, the tablets had to be shredded. After two weeks of treatment with Osilodrostat, UFC was within the URR with serum cortisol 53.8 μg/dl and ACTH 134.7 ng/L. One month later, with a dose of 1 mg + 1.5 mg, serum cortisol remained at 53 µg/dl. After three months, UFC was 179.1 µg/24h, slightly above the URR (176). PET scan using gallium-DOTATATE confirmed a residual pituitary adenoma, suspected due to lack of laboratory tests after surgery. No adverse events from Osilodrostat were observed.

Discussion: We described a case of pediatric Cushing’s disease with recurrence after surgery, which demonstrated a laboratory response to Osilodrostat. This outcome was achieved starting with the minimal dose approved for adults in Europe, then increased by 0.5 mg (2.5 mg/day). Treatment was effective despite the need of shredding the coated tablets. Further studies are required to confirm the efficacy of Osilodrostat in pediatric patients to widen the therapeutic spectrum of Cushing’s disease in this age group.