Which medication blocks cortisol receptors and is used in Cushing syndrome when surgical options are limited?

• A. Ketoconazole
• B. Metyrapone
• C. Mifepristone
• D. Mitotane

Answer: (C)

The main idea is blocking the action of cortisol at its receptor rather than stopping its production. Mifepristone fits this, because it is a glucocorticoid receptor antagonist. By binding to the glucocorticoid receptor, it prevents cortisol from exerting its effects in tissues, so the symptoms of hypercortisolism improve even though cortisol levels may stay high or rise due to loss of feedback signaling.

This mechanism is particularly useful when surgical options are limited or not possible, because you can rapidly blunt cortisol’s actions without needing to reduce its production first. It’s different from drugs that lower cortisol production, like those that inhibit steroid synthesis or damage adrenal tissue; those reduce the amount of cortisol created rather than blocking its receptor.

Keep in mind that blocking glucocorticoid receptors also blocks some progesterone receptors, so pregnancy is contraindicated and there can be effects related to that action. Clinically, because cortisol can’t signal, ACTH and cortisol levels may rise, which means monitoring symptoms and clinical status is more informative than relying on lab cortisol alone.