A 45-year-old man with confirmed Addison disease is on hydrocortisone 15 mg/day and requires mineralocorticoid replacement to correct his persistent hyponatremia (Na 128 mEq/L) and hyperkalemia (K 5.9 mEq/L). Which drug is the preferred mineralocorticoid agent?

Explanation

## Mineralocorticoid Replacement in Addison Disease **Key Point:** Fludrocortisone is the drug of choice for mineralocorticoid replacement in primary adrenal insufficiency. It is a synthetic mineralocorticoid that corrects hyponatremia and hyperkalemia by promoting sodium reabsorption and potassium excretion in the distal tubule. ### Mechanism and Rationale **High-Yield:** Fludrocortisone works by: 1. Activating mineralocorticoid receptors (MR) in the collecting duct 2. Promoting sodium reabsorption via ENaC (epithelial sodium channel) upregulation 3. Increasing potassium secretion and excretion 4. Restoring intravascular volume and blood pressure 5. Typical dose: 0.05–0.2 mg once daily (often 0.1 mg/day) ### Why Fludrocortisone, Not Other Agents? | Agent | Class | Mechanism | Role in Addison | |-------|-------|-----------|------------------| | **Fludrocortisone** | **Synthetic mineralocorticoid** | **Activates MR → ↑ Na reabsorption, ↓ K** | **First-line replacement** | | Spironolactone | Potassium-sparing diuretic | Blocks MR → ↓ Na reabsorption, ↑ K | **Contraindicated** (worsens hyperkalemia) | | Amiloride | Potassium-sparing diuretic | Blocks ENaC → ↓ Na reabsorption, ↑ K | **Contraindicated** (worsens hyperkalemia) | | Lisinopril | ACE inhibitor | Blocks angiotensin II → ↓ aldosterone | **Contraindicated** (worsens hyperkalemia) | **Clinical Pearl:** The combination of hydrocortisone + fludrocortisone is the gold standard for primary adrenal insufficiency. Hydrocortisone alone is insufficient because it has only weak mineralocorticoid activity (~10% of fludrocortisone's potency). Fludrocortisone must be added to normalize serum sodium and potassium. **Warning:** Common mistake — prescribing potassium-sparing diuretics (spironolactone, amiloride) in Addison disease. These agents BLOCK mineralocorticoid action and will worsen hyperkalemia and hyponatremia. They are contraindicated. ### Monitoring During Fludrocortisone Therapy - Check serum sodium and potassium at 1–2 weeks after initiation - Monitor blood pressure (fludrocortisone can cause hypertension and hypokalemia if overdosed) - Adjust dose based on electrolyte response (goal: Na >135 mEq/L, K 3.5–5.0 mEq/L) **Mnemonic:** **FLUDro**cortisone = **FLUID** balance — it's the agent that corrects the fluid and electrolyte abnormalities in Addison disease.