Persistent remission after steroidogenesis inhibitor discontinuation in Cushing disease: a case series

Background Steroidogenesis inhibitors are widely used in the treatment of persistent or recurrent Cushing disease (CD). A few patients who unexpectedly developed adrenal insufficiency (AI) after discontinuation of prolonged osilodrostat therapy were recently described for the first time. Case presentation We report three additional patients with CD who experienced unplanned discontinuation of steroidogenesis inhibitors due to symptoms of AI. All three patients developed symptomatic AI shortly after initiating medical therapy and therefore stopped treatment. Despite drug withdrawal, patients subsequently achieved and maintained biochemical remission, ongoing and observed at the last follow-up visit up to 38 months after drug interruption. Conclusion Long-term remission after interruption of steroidogenesis inhibitors may occur in selected patients with CD. Our cases contribute to the growing literature on potential long-lasting adrenal effects of therapy by providing longer-term follow-up and including metyrapone among the agents involved. These observations support hypotheses of sustained adrenal effects beyond transient enzyme inhibition and underscore the need for prospective studies to identify predictors and mechanisms underlying this unexpected outcome.