osilodrostat and Adrenal-Insufficiency

Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS).. This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS.. A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11).. In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P < .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P < .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P < .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients.. Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.

Topics: Adrenal Insufficiency; Adrenocorticotropic Hormone; Cushing Syndrome; Humans; Hydrocortisone; Prospective Studies; Retrospective Studies

Osilodrostat is the newest approved steroidogenic inhibitor drug for the treatment of hypercortisolism. In this article, we describe 3 patients who experienced a previously undescribed adverse event: a prolonged adrenocortical blockade following treatment cessation.. Patient records showing a history of successful hypercortisolism control with Osilodrostat followed by at least 4 weeks of treatment interruption were reviewed. Patient characteristics and hormonal dosage were analyzed.. Persistence of adrenocortical blockade was found in 3 patients and lasted from 6 weeks to 9 months depending on patients. This phenomenon manifested in patients regardless of lower or higher daily Osilodrostat doses (2-10 mg) and total treatment duration did not seem to predict the severity of the blockade.. The finding of this previously undescribed side effect highlights the importance of continuing adrenal function monitoring after Osilodrostat interruption to prevent adrenal crisis in patients at risk.

Topics: Adrenal Insufficiency; Cushing Syndrome; Humans; Imidazoles; Pyridines

Antisecretory data shows a highly effective and prolonged blockade of cortisol secretion with osilodrostat. The drawback is the occurrence of adrenal insufficiency (AI) in roughly a quarter of treated patients. In this short manuscript, we report three cases of atypical adrenal insufficiency with osilodrostat.

Topics: Adrenal Insufficiency; Humans; Hydrocortisone; Imidazoles; Pituitary ACTH Hypersecretion