Which paraneoplastic endocrine syndrome results from ectopic production of adrenocorticotropic hormone (ACTH) and is most commonly associated with small cell lung cancer?

Explanation

## Ectopic ACTH Syndrome (Cushing Syndrome) as a Paraneoplastic Syndrome **Key Point:** Ectopic ACTH syndrome is a paraneoplastic endocrine syndrome caused by tumor production of ACTH, leading to secondary adrenocorticotropic stimulation and cortisol excess (Cushing syndrome). **High-Yield:** Small cell lung cancer (SCLC) accounts for 50–60% of all ectopic ACTH cases. Other common sources include carcinoid tumors (thymic, bronchial, gastroenteropancreatic) and medullary thyroid carcinoma. ### Pathophysiology ```mermaid flowchart TD A[Tumor produces ACTH] --> B[Stimulates adrenal cortex] B --> C[Increased cortisol production] C --> D[Cushing syndrome manifestations] D --> E[Hypokalemia, hyperglycemia, hypertension] D --> F[Proximal muscle weakness, mood changes] ``` ### Clinical Features of Ectopic ACTH Syndrome | Feature | Characteristic | | --- | --- | | **Onset** | Rapid (weeks to months) | | **Hypokalemia** | Severe, often symptomatic (muscle weakness, arrhythmias) | | **Metabolic alkalosis** | From renal potassium loss | | **Hyperglycemia** | Often severe, may require insulin | | **Hypertension** | Due to mineralocorticoid effects of excess cortisol | | **Proximal myopathy** | Weakness of hip and shoulder girdles | | **Mood disturbances** | Depression, anxiety, psychosis | | **Skin manifestations** | Hyperpigmentation (from elevated ACTH), absence of typical striae and obesity (rapid onset) | ### Diagnostic Approach 1. **24-hour urinary free cortisol:** elevated 2. **Plasma ACTH:** elevated (>200 pg/mL suggests ectopic source) 3. **Low-dose dexamethasone suppression test (LDDST):** no suppression of cortisol (unlike pituitary Cushing) 4. **High-dose dexamethasone suppression test (HDDST):** no suppression (ectopic ACTH is autonomous) 5. **Imaging:** CT/MRI to localize tumor source **Clinical Pearl:** The rapid onset of severe hypokalemia and metabolic alkalosis in a patient with Cushing syndrome should raise suspicion for ectopic ACTH production, particularly in the context of SCLC. **Mnemonic:** **SCLC + ACTH** = **S**mall **C**ell **L**ung **C**ancer produces **ACTH** → rapid, severe Cushing syndrome with prominent hypokalemia.