A 52-year-old man with Cushing syndrome secondary to ectopic ACTH secretion from a small-cell lung cancer presents with severe hypokalemia (K⁺ 2.8 mEq/L), metabolic alkalosis, and acute psychiatric symptoms. Rapid cortisol reduction is needed. Which drug is the most appropriate first-line choice for immediate symptom control in this acute presentation?

Explanation

## Acute Management of Severe Ectopic ACTH Cushing Syndrome ### Clinical Context: Ectopic ACTH Syndrome **Key Point:** Ectopic ACTH-secreting tumours (commonly small-cell lung cancer) produce severe, rapidly progressive Cushing syndrome with profound hypercortisolism, severe hypokalemia, and metabolic derangements requiring urgent intervention. **High-Yield:** In acute, life-threatening hypercortisolism with severe electrolyte disturbance and psychiatric complications, **etomidate** is the drug of choice because it provides rapid cortisol suppression within hours. ### Why Etomidate in Acute Severe Cushing? 1. **Rapid onset:** Inhibits CYP11A1 (P450scc) within 1–2 hours 2. **Potent suppression:** Reduces cortisol levels dramatically 3. **IV administration:** Allows titration in ICU setting 4. **Life-saving in crisis:** Prevents cardiovascular collapse, severe hypokalemia complications, and acute psychosis ### Comparison: Acute vs. Chronic Management | Agent | Setting | Onset | Potency | Reversibility | Indication | |-------|---------|-------|---------|---------------|------------| | **Etomidate** | **ICU/Acute** | **1–2 hours** | **Very high** | **Reversible** | **Life-threatening hypercortisolism** | | Metyrapone | Acute/Chronic | 4–6 hours | High | Reversible | Rapid control; bridge therapy | | Ketoconazole | Chronic | 24–48 hours | Moderate | Reversible | Outpatient; slower onset | | Mitotane | Chronic | Weeks–months | Very high | Irreversible | Long-term; adrenolytic | ### Clinical Pearl **Warning:** Etomidate is an anesthetic agent and must be used in an ICU with continuous monitoring of: - Cortisol levels (target suppression to 50% baseline) - Electrolytes (especially K⁺ — hypokalemia worsens with cortisol reduction) - Cardiovascular status - Sedation level **High-Yield:** The combination of severe hypokalemia, metabolic alkalosis, and acute psychiatric symptoms in this case signals **medical emergency** — etomidate is the only agent that works fast enough to prevent life-threatening complications. ### Next Steps After Acute Stabilization - Once stabilized, transition to metyrapone or ketoconazole for continued outpatient control - Definitive treatment: chemotherapy for small-cell lung cancer - Address hypokalemia aggressively with IV potassium replacement