A 42-year-old man is found to have a unilateral adrenal mass on imaging with biochemical evidence of cortisol excess and suppressed ACTH. Which is the most common cause of ACTH-independent Cushing's syndrome?

Explanation

## Most Common Cause of ACTH-Independent Cushing's Syndrome **Key Point:** Adrenal adenoma is the most common cause of ACTH-independent (primary) Cushing's syndrome, accounting for 40–50% of all Cushing's syndrome cases and ~80% of ACTH-independent cases. **High-Yield:** ACTH-independent Cushing's syndrome occurs when the adrenal gland autonomously produces cortisol without pituitary ACTH drive, resulting in suppressed ACTH levels (typically <5 pg/mL). ### Pathophysiology of ACTH-Independent Cushing's Syndrome **Key Point:** In ACTH-independent disease: 1. Adrenal tumor produces excess cortisol autonomously 2. High cortisol suppresses CRH and ACTH via negative feedback 3. ACTH becomes inappropriately low (<5 pg/mL) despite elevated cortisol 4. The contralateral adrenal gland atrophies from chronic ACTH suppression ### Comparison of ACTH-Independent Causes | Cause | Frequency | Imaging | ACTH Level | Key Feature | |-------|-----------|---------|------------|-------------| | **Adrenal adenoma** | **40–50%** | **Unilateral mass** | **<5 pg/mL** | **Non-functioning contralateral gland, benign** | | Adrenocortical carcinoma | 5–10% | Large, heterogeneous mass | <5 pg/mL | Aggressive, poor prognosis, often >4 cm | | Bilateral macronodular hyperplasia | 5–10% | Bilateral nodules | <5 pg/mL | Both adrenals enlarged, multiple nodules | | PPNAD | <1% | Small, pigmented nodules | <5 pg/mL | Familial (Carney complex), young age, bilateral | **Clinical Pearl:** Adrenal adenomas causing Cushing's syndrome are typically: - **Size:** Usually 2–4 cm (benign threshold often <4 cm) - **Imaging:** Homogeneous, low-density on CT, high lipid content - **Prognosis:** Excellent after surgical resection - **Contralateral gland:** Atrophic due to chronic ACTH suppression **Mnemonic — ACTH-Independent Cushing's Causes (ABPP):** - **A**drenal adenoma (most common) - **B**ilateral macronodular hyperplasia - **P**rimary pigmented nodular adrenocortical disease (PPNAD) - **P**roducing carcinoma (adrenocortical carcinoma) **Warning:** Do not confuse adenoma with carcinoma: - **Adenoma:** Benign, <4 cm, homogeneous, excellent prognosis - **Carcinoma:** Malignant, often >4 cm, heterogeneous, poor prognosis, elevated 17-ketosteroids