A 38-year-old woman presents to the endocrinology clinic with a 6-month history of progressive weight gain (predominantly truncal and supraclavicular), easy bruising, and proximal muscle weakness. She reports amenorrhea for 3 months and recurrent infections. On examination, she has central obesity, purple striae, hirsutism, and acne. Blood pressure is 158/96 mmHg. Laboratory investigations reveal: 24-hour urinary free cortisol 285 µg/day (normal <50), morning plasma cortisol 32 µg/dL (normal 5–25), ACTH 8 pg/mL (normal 10–50), and low-dose dexamethasone suppression test (1 mg overnight) shows cortisol of 28 µg/dL. What is the most likely diagnosis?

Explanation

## Diagnosis: Adrenal Adenoma (ACTH-Independent Cushing Syndrome) ### Clinical Presentation Analysis **Key Point:** The combination of classic Cushing features (truncal obesity, purple striae, proximal weakness, hirsutism, hypertension, amenorrhea) with **suppressed ACTH (8 pg/mL)** is pathognomonic for ACTH-independent Cushing syndrome. ### Diagnostic Algorithm ```mermaid flowchart TD A[Cushing Syndrome Suspected]:::outcome --> B[24-hr UFC elevated + Low LDDS cortisol]:::outcome B --> C{ACTH level?}:::decision C -->|Low/Suppressed| D[ACTH-Independent CS]:::outcome C -->|Normal/High| E[ACTH-Dependent CS]:::outcome D --> F{Imaging: CT adrenal}:::decision F -->|Unilateral adenoma| G[Adrenal Adenoma]:::action F -->|Bilateral hyperplasia| H[Primary Adrenal Hyperplasia]:::action E --> I{Pituitary MRI}:::decision I -->|Adenoma| J[Cushing Disease]:::action I -->|Normal| K[Ectopic ACTH]:::action ``` ### Why This is Adrenal Adenoma | Feature | Finding | Interpretation | |---------|---------|----------------| | **ACTH** | 8 pg/mL (suppressed) | Rules out pituitary/ectopic ACTH source | | **24-hr UFC** | 285 µg/day (elevated) | Confirms autonomous cortisol excess | | **LDDS suppression** | No suppression (28 µg/dL) | Cortisol production is autonomous, not pituitary-driven | | **Clinical phenotype** | Hirsutism, acne, amenorrhea | Suggests adrenal androgen co-secretion (typical of adenoma) | **High-Yield:** In ACTH-independent Cushing syndrome, the suppressed ACTH indicates the pituitary is responding normally to elevated cortisol by shutting off ACTH release — the problem is the adrenal gland itself. ### Confirmatory Step **Clinical Pearl:** High-dose dexamethasone suppression test (8 mg overnight) would show **no suppression** (cortisol remains >50% of baseline), confirming adrenal autonomy rather than pituitary-dependent disease. **Key Point:** CT or MRI of the adrenal glands would demonstrate a unilateral adenoma, confirming the diagnosis. Adenomas are typically <4 cm, lipid-rich (negative Hounsfield units on CT), and show rapid washout on contrast-enhanced imaging. ### Differential Considerations - **Pseudo-Cushing:** Ruled out by suppressed ACTH and elevated UFC; pseudo-Cushing typically shows normal UFC and normal ACTH. - **Ectopic ACTH:** Would present with elevated ACTH (usually >100 pg/mL), not suppressed. - **Pituitary adenoma:** Would show normal or elevated ACTH, not suppressed.