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

Explanation

## Most Common Cause of Cushing Syndrome ### Epidemiology of Cushing Syndrome Causes **Key Point:** Pituitary corticotroph adenoma (Cushing disease) accounts for approximately 70–80% of all cases of endogenous Cushing syndrome, making it by far the most common cause. ### Classification by Frequency | Cause | Frequency | ACTH Status | Plasma ACTH Level | |-------|-----------|-------------|-------------------| | **Pituitary adenoma (Cushing disease)** | **70–80%** | **Elevated** | **20–200 pg/mL** | | Adrenocortical adenoma | 10–15% | Suppressed | <5 pg/mL | | Ectopic ACTH secretion | 5–10% | Elevated | Often >200 pg/mL | | Adrenocortical carcinoma | 5–10% | Variable | Variable | | Primary pigmented nodular adrenocortical disease (PPNAD) | <1% | Suppressed | <5 pg/mL | ### Why Pituitary Adenoma Is Most Common **High-Yield:** Pituitary corticotroph adenomas are typically small (<10 mm), slow-growing benign tumors that arise from the anterior pituitary. They account for the vast majority of ACTH-dependent Cushing syndrome (Cushing disease). **Clinical Pearl:** Cushing disease (pituitary source) is distinct from Cushing syndrome (the clinical syndrome of cortisol excess). Cushing disease is the most common cause of Cushing syndrome. ### Diagnostic Approach ```mermaid flowchart TD A[Confirmed Cushing Syndrome]:::outcome --> B{Plasma ACTH level?}:::decision B -->|Suppressed <5 pg/mL| C[ACTH-independent]:::outcome B -->|Elevated >20 pg/mL| D[ACTH-dependent]:::outcome C --> E{High-dose dexamethasone suppression?}:::decision D --> F{High-dose dexamethasone suppression?}:::decision E -->|Suppression| G[Pituitary adenoma]:::action E -->|No suppression| H[Adrenocortical carcinoma]:::action F -->|Suppression| I[Pituitary adenoma - Cushing disease]:::action F -->|No suppression| J[Ectopic ACTH or adrenal source]:::action ``` **Key Point:** The high-dose dexamethasone suppression test (8 mg overnight or 2 mg/6 hours × 2 days) differentiates pituitary adenoma (suppression occurs) from ectopic ACTH or adrenal causes (no suppression). ### Mnemonic for Cushing Syndrome Causes **Mnemonic:** **ACTH** — **A**denoma (pituitary), **C**arcinoma (adrenal), **T**umor (ectopic), **H**yperplasia (rare) [cite:Harrison 21e Ch 375]