A 38-year-old woman presents with progressive central obesity, proximal muscle weakness, and purple striae. Laboratory investigations reveal elevated 24-hour urinary free cortisol and loss of normal diurnal cortisol rhythm. Which is the most common cause of Cushing syndrome in this patient?

Explanation

## Most Common Cause of Cushing Syndrome **Key Point:** Pituitary adenoma (specifically corticotroph adenoma) accounts for approximately 70% of all cases of endogenous Cushing syndrome, making it the most common cause by far. ## Epidemiology of Cushing Syndrome Causes | Cause | Frequency | ACTH Level | Dexamethasone Suppression | |-------|-----------|-----------|-------------------------| | **Pituitary adenoma** | **~70%** | **Elevated** | **Suppressed at high dose** | | Adrenocortical carcinoma | ~10% | Low/absent | Not suppressed | | Ectopic ACTH (lung, thymus) | ~15% | Very elevated | Not suppressed | | Primary adrenal hyperplasia | ~5% | Low/absent | Not suppressed | ## Clinical Context in This Case **High-Yield:** The patient presents with classic Cushing syndrome features (central obesity, proximal weakness, striae) and has elevated UFC with loss of diurnal rhythm—all consistent with ACTH-dependent disease. The next diagnostic step would be: 1. Measure plasma ACTH (will be elevated in pituitary adenoma) 2. Perform low-dose dexamethasone suppression test (LDST) 3. If ACTH elevated and LDST shows suppression → pituitary source 4. Confirm with high-dose dexamethasone suppression test (HDST) or MRI pituitary **Clinical Pearl:** Pituitary adenomas causing Cushing syndrome are usually **microadenomas** (<10 mm) and may not be visible on standard MRI, requiring dynamic pituitary MRI or inferior petrosal sinus sampling (IPSS) for localization. **Mnemonic:** **PACE** — Pituitary (70%), Adrenal (10%), Carcinoma ectopic (15%), Everything else (5%). ## Why Pituitary Adenoma is Most Common - Corticotroph adenomas are the most frequent functional pituitary tumor - Usually benign microadenomas with slow growth - Female predominance (3:1), typically age 30–50 years - Responsive to both low-dose and high-dose dexamethasone suppression (distinguishes from ectopic ACTH) [cite:Harrison 21e Ch 375]