How does ketoconazole achieve its therapeutic effect in a patient with Cushing's disease?

Ketoconazole achieves its therapeutic effect in a patient with Cushing's disease by inhibiting cortisol synthesis enzymes. In cases of Cushing's disease, there is an overproduction of cortisol, often due to an adrenal tumor or pituitary adenoma that produces excess adrenocorticotropic hormone (ACTH). Ketoconazole acts as an antifungal medication, but it also possesses anti-androgenic properties and inhibits the enzymes involved in the synthesis of steroids from cholesterol in the adrenal cortex.

By blocking the enzyme 17α-hydroxylase and other enzymes in the steroidogenesis pathway, ketoconazole effectively reduces the production of cortisol. This decrease in cortisol levels helps alleviate the symptoms associated with Cushing's disease, such as weight gain, hypertension, and skin changes.

Understanding the mechanism of how ketoconazole works is crucial for managing Cushing's disease, as the goal is to restore hormonal balance by reducing elevated cortisol levels while avoiding the addition of other hormones, such as aldosterone, which could exacerbate the condition.