In a patient with ACTH-dependent Cushing syndrome, a high-dose dexamethasone suppression test (8 mg overnight) shows suppression of cortisol. What is the most likely diagnosis?

Explanation

## High-Dose Dexamethasone Suppression Test (HDST) in ACTH-Dependent Cushing Syndrome **Key Point:** The high-dose dexamethasone suppression test (8 mg overnight or 2 mg every 6 hours for 48 hours) is used to differentiate pituitary ACTH-secreting adenoma from ectopic ACTH secretion. **Suppression of cortisol (>50% reduction from baseline) indicates pituitary adenoma; lack of suppression suggests ectopic ACTH.** ### Diagnostic Algorithm for ACTH-Dependent Cushing Syndrome ```mermaid flowchart TD A[Cushing Syndrome confirmed]:::outcome --> B[Measure plasma ACTH]:::action B --> C{ACTH level}:::decision C -->|Low/undetectable| D[ACTH-independent]:::outcome C -->|Elevated| E[ACTH-dependent]:::outcome E --> F[Low-dose DST suppression?]:::decision F -->|Yes| G[Likely pituitary or ectopic]:::outcome F -->|No| H[Ectopic likely]:::outcome G --> I[High-dose DST 8 mg]:::action I --> J{Cortisol suppression >50%?}:::decision J -->|Yes| K[Pituitary adenoma Cushing disease]:::action J -->|No| L[Ectopic ACTH secretion]:::action ``` ### Dexamethasone Suppression Test Interpretation | Test | Pituitary Adenoma | Ectopic ACTH | Adrenal Tumor | | --- | --- | --- | --- | | **Low-dose DST (1 mg)** | No suppression | No suppression | No suppression | | **High-dose DST (8 mg)** | **Suppression (>50%)** | **No suppression** | No suppression | | **Plasma ACTH** | Elevated (10–200 pg/mL) | Very elevated (>200 pg/mL) | Suppressed (<5 pg/mL) | | **CRH stimulation test** | **ACTH ↑ (paradoxical)** | **No response** | No response | **High-Yield:** The high-dose dexamethasone suppression test is the gold standard for distinguishing pituitary from ectopic ACTH secretion. Pituitary adenomas retain some feedback sensitivity to high-dose glucocorticoids, whereas ectopic ACTH-secreting tumours are autonomous and do not suppress. **Clinical Pearl:** In ectopic ACTH syndrome (especially small-cell lung cancer), cortisol levels are often very high (>50 μg/dL), and the clinical presentation may be atypical (rapid onset, hypokalemia, metabolic alkalosis) due to the severity of hypercortisolism. **Mnemonic:** **HDST Suppression = Pituitary** — High-Dose Suppression Test positive (cortisol suppresses) = pituitary adenoma; negative = ectopic.