Evaluating Clinical and Real-World Evidence in Hypercortisolism

This episode, titled ‘Evaluating Clinical and Real-World Evidence in Hypercortisolism,’ features panelists discussing key clinical trial findings, real-world treatment experiences, and emerging research that continue to shape the management of hypercortisolism. The expert faculty review efficacy, safety, and practical considerations associated with several established therapies while also exploring new insights into the relationship between cortisol excess and metabolic dysfunction.

The panel of experts begins by examining data from the SONICS trial evaluating levoketoconazole. They discuss treatment response rates, durability of cortisol control, and important safety considerations, including liver-related adverse events, QT interval prolongation, hypokalemia, and musculoskeletal symptoms. Faculty members also consider patient characteristics that may influence treatment selection, including the presence of hyperglycemia, liver disease, and hyperandrogenism.

The conversation then turns to mifepristone, a glucocorticoid receptor antagonist that has been used for more than a decade in patients with hypercortisolism and hyperglycemia. Panelists review both clinical trial and real-world evidence demonstrating improvements in glycemic control, body weight, and metabolic outcomes. They also discuss practical challenges associated with therapy, including the absence of biochemical markers to monitor treatment response and the importance of managing adverse effects such as hypokalemia, glucocorticoid withdrawal symptoms, and gynecologic complications.

The discussion concludes with an exploration of findings from the CATALYST and MOMENTUM studies, which have expanded understanding of how cortisol excess affects endogenous incretin pathways. The faculty examine emerging evidence linking hypercortisolism to impaired GLP-1 and GIP activity and discuss how modulation of cortisol signaling may influence responses to incretin-based therapies. Together, these insights highlight the evolving evidence base guiding treatment decisions and metabolic management in hypercortisolism.

In the next episode, ‘Long-Term Treatment Adherence and Persistence in Hypercortisolism’, panelists will discuss the factors that influence long-term treatment success, including patient education, medication tolerability, monitoring requirements, and healthcare access. The expert faculty will also explore practical strategies for improving adherence, managing adverse effects, and supporting sustained disease control over time.