Hypokalemia associated with mifepristone use in the treatment of Cushing’s syndrome

SUMMARY: Mifepristone is a promising option for the management of hypercortisolism associated with hyperglycemia. However, its use may result in serious electrolyte imbalances, especially during dose escalation. In our patient with adrenocorticotropic hormone-independent macro-nodular adrenal hyperplasia, unilateral adrenalectomy resulted in biochemical and clinical improvement, but subclinical hypercortisolism persisted following adrenalectomy. She was started on mifepristone. Unfortunately, she missed her follow-up appointments following dosage escalation and required hospitalization at an intensive care level for severe refractory hypokalemia. LEARNING POINTS: 1. Mifepristone, a potent antagonist of glucocorticoid receptors, has a high risk of adrenal insufficiency, despite high cortisol levels. 2. Mifepristone is associated with hypokalemia due to spill-over effect of cortisol on unopposed mineralocorticoid receptors. 3. Given the lack of a biochemical parameter to assess improvement, the dosing of mifepristone is based on clinical progress. 4. Patients on mifepristone require anticipation of toxicity, especially when the dose is escalated. 5. The half-life of mifepristone is 85 h, requiring prolonged monitoring for toxicity, even after the medication is held.