A 42-year-old woman from Delhi presents with progressive central obesity, proximal muscle weakness, and easy bruising for 8 months. On examination, she has a moon facies, supraclavicular fat pads, and purple striae on the abdomen. Blood pressure is 156/98 mmHg. Laboratory investigations show: 24-hour urinary free cortisol 285 µg/day (normal <50), morning plasma cortisol 28 µg/dL, and ACTH 8 pg/mL (normal 10–46). A low-dose dexamethasone suppression test (LDDST) shows cortisol of 18 µg/dL after 1 mg dexamethasone. What is the most likely diagnosis?

Explanation

## Diagnostic Approach to Cushing Syndrome **Key Point:** The suppressed ACTH level (8 pg/mL, well below the normal range) in the presence of elevated cortisol and elevated 24-hour urinary free cortisol is the critical finding that distinguishes ACTH-independent from ACTH-dependent Cushing syndrome. ### Step-by-Step Analysis 1. **Confirm hypercortisolism:** - 24-hour urinary free cortisol 285 µg/day (markedly elevated; normal <50) - Morning plasma cortisol 28 µg/dL (elevated; normal 5–25) - LDDST cortisol 18 µg/dL (fails to suppress; normal <1.8 after 1 mg dexamethasone) - **Diagnosis of Cushing syndrome is confirmed.** 2. **Determine ACTH dependence:** - ACTH is **suppressed** at 8 pg/mL (normal range 10–46) - This indicates **ACTH-independent** (primary adrenal) Cushing syndrome - In ACTH-dependent disease (pituitary or ectopic), ACTH would be elevated or inappropriately normal 3. **Differential of ACTH-independent Cushing:** - **Adrenal adenoma** (most common cause of ACTH-independent Cushing; ~40% of all Cushing syndrome) - Adrenal carcinoma (usually with very high cortisol and virilization) - Primary bilateral adrenal hyperplasia (rare; usually ACTH-dependent) **Clinical Pearl:** In adrenal adenoma, the suppressed ACTH reflects negative feedback from excess cortisol on the normal pituitary. The contralateral adrenal gland is suppressed and atrophic. **High-Yield:** The LDDST result (18 µg/dL) shows failure of suppression, which is expected in primary adrenal disease—the adenoma produces cortisol autonomously regardless of dexamethasone. ### Why Adrenal Adenoma is Most Likely - **Classic presentation:** Central obesity, proximal weakness, hypertension, easy bruising, moon facies, supraclavicular fat pads, purple striae - **Suppressed ACTH:** Pathognomonic for adrenal (not pituitary or ectopic) source - **Imaging confirmation:** CT/MRI adrenal would show a unilateral mass (typically <4 cm, benign-appearing) - **Biochemistry:** High cortisol + low ACTH = adrenal adenoma until proven otherwise ### Mnemonic: ACTH-Independent Cushing Causes **ADRENAL** — Adenoma, Carcinoma, (rarely) Bilateral hyperplasia **Warning:** Do not confuse suppressed ACTH with pituitary disease. In Cushing disease (pituitary adenoma), ACTH is elevated or inappropriately normal-range; it does NOT suppress below 5 pg/mL.