Mifepristone Therapy for Cushing's Syndrome

Efficacy and Safety

The American College of Endocrinology recommends mifepristone for controlling hyperglycemia in Cushing's syndrome patients who have failed surgery or are not surgical candidates, with 38% of patients showing significant improvement in glucose control, and improvements in insulin resistance, weight, waist circumference, and quality of life 1
Mifepristone treatment results in elevated cortisol levels due to its mechanism of blocking the glucocorticoid receptor, requiring expert management and close monitoring for hypokalemia, hypertension, and adrenal insufficiency 1, 2, 3

The Endocrine Society guideline highlights the inability to monitor cortisol levels biochemically during mifepristone treatment, making it fundamentally different from other medical therapies, and requiring clinical features to guide management 1, 2, 3
Mifepristone is associated with serious adverse events, including hypokalemia and hypertension, which occurred in 12 patients in the pivotal study, and adrenal insufficiency, which required dexamethasone treatment in 7 patients 1, 2

The Endocrine Society recommends that adrenal steroidogenesis inhibitors are usually used first for Cushing's disease, given their reliable effectiveness and ability to monitor cortisol levels, while mifepristone may be preferred in specific scenarios, such as patients with severe hyperglycemia or men who need to avoid hypogonadism 1, 2
Mifepristone should not be used as first-line medical therapy for Cushing's disease, but may be considered as bridge therapy or when other medical therapies have failed or are not tolerated 1, 2, 4

Mifepristone is not currently approved for pediatric use, and effects and safety are being evaluated in a phase II trial in children, with medical therapy in children and adolescents confined to normalizing cortisol levels in preparation for surgery or while awaiting response to radiotherapy 5

Mifepristone should only be prescribed by clinicians with extensive experience in Cushing's disease management, due to the inability to use biochemical markers for monitoring and the increased risk of unrecognized adrenal insufficiency 2, 3