Response to Osilodrostat Therapy in Adrenal Cushing’s Syndrome

Abstract

Cushing’s disease (CD) is the most common cause of endogenous hypercortisolism. Osilodrostat was demonstrated to be efficient in treating CD, and the mean average dose required for CD control was <11 mg/day. Potential differences in osilodrostat treatment between cortisol-producing adenoma (CPA) and CD have not been reported. The aim of this study was to present two patients with CPA in whom significant differences in the response to therapy compared to CD were found. We demonstrated a case of inverse response of cortisol levels with adrenal tumor progression during the initial dose escalation (Case 1). Simultaneously, severe exaggeration of hypercortisolism symptoms and life-threatening hypokalemia occurred. A further rapid dose increase resulted in the first noticeable cortisol response at a dose of 20 mg/day, and a full response at a dose of 45 mg/day. We also present a case that was initially resistant to therapy (Case 2). The doses required to achieve the first response and the full response were the same as those for Case 1. Our study demonstrated that osilodrostat therapy in patients with CPA may require a different approach than that in CD, with higher doses, faster dose escalation, and a possible initial inverse response or lack of response.

Keywords:

• osilodrostat
• adrenal adenoma
• hypercortisolism
• ACTH-independent
• adverse events
• hypokalemia

Acknowledgments

The abstract included some parts of this paper was presented at the European Congress of Endocrinology ECE2023 as a rapid communication. The abstract was published in the Endocrine Abstracts Vol. 90 [https://www.endocrine-abstracts.org/ea/0090/].

Disclosure

Professor Przemysław Witek reports personal fees from Investigator in the clinical trials paid by Novartis and Recordati Rare Diseases, outside the submitted work; lectures fees from Recordati Rare Diseases, Strongbridge, IPSEN. The authors report no other conflicts of interest in this work.

Additional information

Funding

The publication of this report was financially supported by the statutory funds of the Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland.