A 38-year-old woman presents with a 6-month history of progressive central obesity, proximal muscle weakness, and easy bruising. She reports irregular menses and mood disturbances. On examination, she has a round 'moon facies', dorsocervical fat pad, and purple striae on her abdomen. Blood pressure is 158/96 mmHg. Laboratory investigations show: 24-hour urinary free cortisol 450 µg/day (normal <100), morning plasma cortisol 28 µg/dL (normal 5–25), and ACTH 8 pg/mL (normal 10–50). A low-dose dexamethasone suppression test (LDDST) shows cortisol of 22 µg/dL after 1 mg dexamethasone overnight. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: ACTH-Independent Cushing Syndrome (Adrenal Adenoma) ### Key Diagnostic Features **Key Point:** The combination of suppressed ACTH (8 pg/mL, well below normal range) with elevated cortisol and non-suppression on LDDST is pathognomonic for ACTH-independent Cushing syndrome, most commonly due to an adrenal adenoma. ### Pathophysiology In adrenal adenoma-induced Cushing syndrome: 1. Autonomous cortisol production by the adenoma suppresses pituitary ACTH via negative feedback 2. ACTH levels fall to very low levels (<5 pg/mL typical) 3. The tumor produces cortisol independent of ACTH stimulation 4. Dexamethasone cannot suppress the autonomous adenoma's cortisol production ### Diagnostic Algorithm ```mermaid flowchart TD A[Cushing Syndrome Confirmed<br/>High UFC, High Morning Cortisol<br/>No LDDST Suppression]:::outcome --> B{ACTH Level?}:::decision B -->|Low/Suppressed<br/>< 5 pg/mL| C[ACTH-Independent<br/>Cushing]:::outcome B -->|Normal-High<br/>> 20 pg/mL| D[ACTH-Dependent<br/>Cushing]:::outcome C --> E{Imaging: CT/MRI<br/>Adrenal}:::decision E -->|Unilateral mass| F[Adrenal Adenoma]:::action E -->|Bilateral masses| G[Adrenal Carcinoma or<br/>Bilateral Hyperplasia]:::action D --> H[Pituitary MRI]:::action H -->|Adenoma seen| I[Cushing Disease<br/>Pituitary Adenoma]:::outcome H -->|No adenoma| J[Ectopic ACTH]:::outcome ``` ### Why This Patient Has Adrenal Adenoma | Feature | Finding | Interpretation | |---------|---------|----------------| | **ACTH** | 8 pg/mL (suppressed) | Rules out pituitary and ectopic ACTH sources | | **24-h UFC** | 450 µg/day (elevated) | Confirms cortisol excess | | **Morning cortisol** | 28 µg/dL (high-normal to elevated) | Autonomous production | | **LDDST response** | No suppression (22 µg/dL) | Adenoma is autonomous, not ACTH-driven | | **Clinical features** | Classic Cushing phenotype | Consistent with any form of Cushing | **High-Yield:** Low ACTH + high cortisol + no LDDST suppression = **adrenal adenoma** (most common ACTH-independent cause). Next step: **CT abdomen to visualize the adenoma**. ### Clinical Pearl Adrenal adenomas account for ~15–20% of all Cushing syndrome cases. They are typically unilateral, benign, and <4 cm. Treatment is **unilateral adrenalectomy**. Unlike pituitary adenomas, there is no role for pituitary surgery or radiation. [cite:Harrison 21e Ch 375]