A 38-year-old woman presents with a 6-month history of progressive weight gain (predominantly truncal and facial), easy bruising, and amenorrhea. On examination, she has a moon facies, central obesity with supraclavicular fat pads, and purple striae on her abdomen. Blood pressure is 158/98 mmHg. Laboratory investigations show: 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). A low-dose dexamethasone suppression test (1 mg overnight) shows cortisol of 28 µg/dL. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: ACTH-Independent Cushing Syndrome (Adrenal Adenoma) ### Key Clinical Features **Key Point:** The combination of elevated 24-hour urinary free cortisol, elevated morning cortisol, and **suppressed ACTH (8 pg/mL, well below normal range)** with failure to suppress on low-dose dexamethasone (LDDST) indicates an **autonomous cortisol-producing adrenal lesion**. ### Diagnostic Algorithm ```mermaid flowchart TD A[Clinical features of Cushing syndrome]:::outcome --> B[24-hr UFC elevated + Morning cortisol elevated]:::outcome B --> C{ACTH level?}:::decision C -->|Low/Suppressed| D[ACTH-Independent Cushing]:::outcome C -->|Normal/High| E[ACTH-Dependent Cushing]:::outcome D --> F{LDDST suppression?}:::decision F -->|No suppression| G[Adrenal adenoma or carcinoma]:::action E --> H[Pituitary vs Ectopic ACTH]:::action ``` ### Why This Is Adrenal Adenoma 1. **Suppressed ACTH (8 pg/mL):** The low ACTH indicates the pituitary is being suppressed by autonomous cortisol production from the adrenal gland. The adrenal tumor produces cortisol independent of ACTH stimulation. 2. **No suppression on LDDST:** The adenoma continues to produce cortisol despite high-dose dexamethasone exposure, confirming autonomous function. 3. **Classic clinical presentation:** Moon facies, truncal obesity, purple striae, hypertension, and amenorrhea are typical of chronic hypercortisolism. **High-Yield:** ACTH-independent Cushing syndrome accounts for ~15–20% of all Cushing cases. The **suppressed ACTH is the key discriminator** — it rules out pituitary and ectopic ACTH sources. ### Differential Diagnosis Table | Feature | Pituitary ACTH | Ectopic ACTH | Adrenal Adenoma | | --- | --- | --- | --- | | **ACTH level** | Elevated (20–100) | Very elevated (>200) | **Suppressed (<5)** | | **24-hr UFC** | Elevated | Very elevated | Elevated | | **LDDST suppression** | Yes (>50% drop) | No suppression | No suppression | | **HDDST suppression** | Yes (>50% drop) | No suppression | No suppression | | **Imaging** | Pituitary adenoma | Lung/chest mass | Adrenal nodule | **Clinical Pearl:** In adrenal adenomas, the suppressed ACTH reflects negative feedback from the elevated cortisol on the normal pituitary-hypothalamic axis. The adenoma is **ACTH-independent** — it does not require ACTH to produce cortisol. ### Next Steps - **CT/MRI adrenal:** To visualize the adenoma and exclude adrenal carcinoma (size >4 cm, heterogeneous enhancement, invasion suggest carcinoma). - **Adrenal vein sampling:** Not needed if imaging is diagnostic; reserved for bilateral nodules or equivocal imaging. - **Treatment:** Unilateral adrenalectomy is curative for adenomas. [cite:Harrison 21e Ch 375]