Updates in adrenal steroidogenesis inhibitors for Cushing's syndrome - A practical guide

Medical therapy is essential in the management of patients with Cushing's syndrome (CS) when curative surgery has failed, surgery is not feasible, when awaiting radiation effect, and in recurrent cases of CS. Steroidogenesis inhibitors have a rapid onset of action and are effective in reducing hypercortisolism, however, adverse effects, including adrenal insufficiency require very close patient monitoring. Osilodrostat is the only steroidogenesis inhibitor to have been assessed in prospective randomized controlled trials and approved for Cushing's disease (CD) by the US Food and Drug Administration and for CS by the European Medical Agency (EMA). Osilodrostat has been shown to be highly effective at maintaining normal urinary free cortisol in patients with CD. Drugs such as metyrapone, ketoconazole (both EMA approved), and etomidate lack prospective evaluation(s). There is, however, considerable clinical experience and retrospective data that show a very wide efficacy range in treating patients with CS. In the absence of head-to-head comparative clinical trials, therapy choice is determined by the specific clinical setting, risk of adverse events, cost, availability, and other factors. In this review practical points to help clinicians who are managing patients with CS being treated with steroidogenesis inhibitors are presented. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

Medical therapy with steroidogenesis inhibitors is crucial in managing patients with Cushing's syndrome when surgery is not an option, failed, or recurrence occurs. Among these inhibitors, osilodrostat has shown high efficacy and has been approved for treating Cushing's disease by the FDA and CS by the EMA. Other options like metyrapone, ketoconazole, and etomidate lack prospective evaluations but have shown varied efficacy in treating CS patients.