In a patient with elevated cortisol levels that decrease significantly with high-dose dexamethasone, what is the most likely underlying cause?

In a patient with elevated cortisol levels that significantly decrease with high-dose dexamethasone, the underlying cause is most likely a pituitary adenoma. This response is based on the feedback mechanism of the hypothalamic-pituitary-adrenal (HPA) axis.

In cases of Cushing's disease, which is caused by a pituitary adenoma, there is excessive ACTH production leading to increased cortisol secretion from the adrenal glands. When high doses of dexamethasone, a potent glucocorticoid, are administered, they suppress ACTH secretion from the pituitary. As a result, cortisol levels drop significantly due to this negative feedback mechanism. This differentiation is key because if the source of high cortisol levels were due to ectopic ACTH production or an adrenal adenoma, high doses of dexamethasone would not lead to a significant decrease in cortisol levels.

Ectopic ACTH production typically does not depend on feedback inhibition from dexamethasone, while adrenal adenomas function independently of ACTH regulation. Surreptitious use of steroids would not present with this specific pattern, as external corticosteroids could suppress endogenous production but would not mimic the elevated cortisol levels originating from an ACTH-dependent