Mifepristone (RU-486) is a competitive antagonist at the progesterone receptor used for medical termination of pregnancy. It also has glucocorticoid receptor (GR) antagonism, making it useful in which condition?

• A Addison's disease to replace cortisol when mineralocorticoid deficiency does not accompany glucocorticoid deficiency
• B Congenital adrenal hyperplasia to suppress ACTH-driven androgen excess through feedback suppression
• C Asthma exacerbation where inhaled corticosteroids have failed, to counteract chronic GR downregulation
• D Cushing's syndrome — specifically for the hyperglycaemia of hypercortisolism (Korlym indication) — blocking peripheral glucocorticoid receptor effects on glucose metabolism without lowering cortisol levels ✓

Explanation

Mifepristone's GR antagonism is exploited clinically in endogenous Cushing's syndrome to control hypercortisolism-induced hyperglycaemia/diabetes when surgery is not immediately feasible or has failed. Since it blocks glucocorticoid action at peripheral receptors rather than reducing cortisol levels, serum cortisol and ACTH rise (feedback is also blocked), but the peripheral metabolic consequences (hyperglycaemia, protein catabolism) are reduced. This distinguishes its mechanism from steroidogenesis inhibitors like ketoconazole, metyrapone, or osilodrostat which lower cortisol production. Mifepristone's GR antagonism also explains why monitoring cannot use serum cortisol levels.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.