Practical Use of Mifepristone and the Need for Endocrinology–Primary Care Collaboration

In this segment, Ralph DeFronzo, MD, elaborates on the practical magnitude of benefit observed with mifepristone in hypercortisolism, particularly in patients enrolled in trials like CATALYST. He reiterates that beyond the approximately 1.5–percentage point drop in hemoglobin A1c, patients experienced average weight loss of roughly 5 kg and a 5.1-cm reduction in waist circumference—changes that translate to meaningful alterations in body habitus. From a diabetes-management perspective, such improvements, combined with marked reductions in insulin dose, signal a fundamental shift in the underlying pathophysiology rather than incremental pharmacologic fine-tuning.

However, Dr DeFronzo and Richard Auchus, MD, candidly describe real-world barriers to safe and confident use of mifepristone, particularly in primary care. DeFronzo recounts an early CATALYST patient who developed glucocorticoid withdrawal symptoms, sought care from a primary physician unfamiliar with the trial, and was advised to stop the medication over concerns about adrenal crisis. This anecdote highlights how lack of familiarity with withdrawal phenomena and the expected rise in serum cortisol can lead to premature discontinuation or misinterpretation of adverse effects. Managing hypokalemia via spironolactone and other supportive strategies requires an understanding of the drug’s mechanistic profile and a proactive approach to monitoring.

To address these challenges, the faculty advocate for close collaboration between primary care and endocrinology. Primary care clinicians are best positioned to recognize high-risk patients—those with refractory diabetes and hypertension on multiple agents—whereas endocrinologists bring experience in interpreting hormone tests, managing cortisol-directed therapies, and counseling patients through withdrawal symptoms. Dr DeFronzo notes that manufacturers of mifepristone sponsor support programs that can help guide dosing, monitoring, and side-effect management for clinicians new to the therapy. Collectively, the speakers argue that a team-based model, with clear referral pathways and shared care, is essential to realizing the full potential of mifepristone in broader hypercortisolism management.