A 45-year-old woman presents with progressive weight gain over 2 years, with fat redistribution to the face and upper back. On examination, she demonstrates the classic features marked **A** in the diagram: moon facies, buffalo hump, and broad violaceous abdominal striae. Laboratory investigation reveals elevated 24-hour urinary free cortisol (4.2× upper limit of normal) and failure to suppress cortisol below 1.8 μg/dL on overnight 1 mg dexamethasone suppression test. Subsequent ACTH measurement is 8 pg/mL. Which of the following is the most appropriate next diagnostic step?

Question

Accepted Answer

A. Adrenal CT/MRI to localize the source of cortisol excess. ## Why Adrenal CT/MRI is correct The clinical features marked **A** (moon facies, buffalo hump, violaceous striae) are the classic phenotype of Cushing syndrome caused by chronic glucocorticoid excess. The ACTH level of 8 pg/mL is suppressed (<5 pg/mL threshold for ACTH-independent disease), indicating the source of cortisol is the adrenal gland itself, not the pituitary or ectopic ACTH-secreting tissue. According to the Endocrine Society Cushing Syndrome Guidelines 2015, after confirming Cushing syndrome and measuring ACTH to distinguish ACTH-dependent from ACTH-independent disease, the next step for ACTH-independent Cushing is **adrenal imaging (CT or MRI)** to identify whether the lesion is an adenoma, carcinoma, or hyperplasia. ## Why each distractor is wrong - **Pituitary MRI and high-dose dexamethasone suppression test**: These are appropriate for ACTH-dependent Cushing syndrome (ACTH >15 pg/mL), not ACTH-independent disease. The low ACTH rules out pituitary adenoma (Cushing disease) as the source. - **Inferior petrosal sinus sampling with CRH stimulation**: IPSS is the gold standard to differentiate pituitary from ectopic ACTH sources in ACTH-dependent Cushing syndrome. It is not indicated when ACTH is suppressed, as the problem is adrenal, not pituitary or ectopic. - **Chest CT and screening for small-cell lung carcinoma**: Ectopic ACTH secretion (e.g., from small-cell lung carcinoma) would present with elevated ACTH (>15 pg/mL), not suppressed ACTH. This patient's low ACTH excludes ectopic ACTH syndrome. **High-Yield:** ACTH-independent Cushing (ACTH <5 pg/mL) → adrenal imaging; ACTH-dependent Cushing (ACTH >15 pg/mL) → pituitary MRI ± IPSS. [cite: Endocrine Society Cushing Syndrome Guidelines 2015]

Answer

B. Pituitary MRI and high-dose dexamethasone suppression test

Answer

C. Inferior petrosal sinus sampling with CRH stimulation

Answer

D. Chest CT and screening for small-cell lung carcinoma

Explanation

Why Adrenal CT/MRI is correct

Why each distractor is wrong

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