Reading the cortisol and ACTH pattern
Cortisol production is controlled by the hypothalamic-pituitary-adrenal axis. The pituitary secretes adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to make cortisol, and cortisol in turn suppresses ACTH through negative feedback. A cortisol-secreting adrenal tumor produces cortisol on its own, independent of ACTH. The high cortisol then suppresses the pituitary, so ACTH falls. High cortisol with low ACTH shows that the adrenal mass, not the pituitary, is the source.
Contrasting the other sources
In Cushing disease, a pituitary adenoma secretes ACTH, so ACTH is high or inappropriately normal despite high cortisol; the tumor does not respond normally to feedback. In ectopic ACTH syndrome, a non-pituitary tumor such as a lung tumor secretes ACTH, often at very high levels, and the intense cortisol excess can cause low potassium through mineralocorticoid effects. In both cases, ACTH is not suppressed. Her 3-cm adrenal mass, the absence of corticosteroid use, and the expected low ACTH fit an adrenal source.
| Pattern | Likely source |
|---|
| High cortisol, low ACTH | Adrenal tumor (ACTH-independent) |
| High cortisol, normal ACTH | Pituitary (ACTH not suppressed) |
| High cortisol, high ACTH | Pituitary adenoma or ectopic source |
| High cortisol, very high ACTH, low potassium | Ectopic ACTH, such as a lung tumor |
Why the distractors are wrong
A normal ACTH may sound reassuring, but in the presence of high cortisol it is inappropriate; a healthy pituitary would be suppressed, so a normal value points to a pituitary source. High ACTH clearly points to a pituitary or ectopic source. The combination with low potassium suggests an ectopic tumor. Watch out! Always interpret ACTH in relation to cortisol; a value in the normal range is abnormal when cortisol is high.
Exam takeaway
Cushing syndrome can come from exogenous corticosteroids, a pituitary adenoma, an ectopic ACTH source, or an adrenal tumor. She has never taken corticosteroids, so an exogenous cause is excluded. Key point! ACTH-independent Cushing syndrome from an adrenal tumor shows high cortisol with suppressed (low) ACTH.