A 38-year-old woman presents with progressive fatigue, weight loss, and hyperpigmentation. Investigations reveal serum sodium 128 mEq/L, potassium 5.8 mEq/L, and a low morning cortisol of 3 µg/dL with elevated ACTH of 85 pg/mL. A diagnosis of primary adrenal insufficiency (Addison disease) is confirmed. What is the drug of choice for glucocorticoid replacement in this patient?

Explanation

## Glucocorticoid Replacement in Addison Disease **Key Point:** Hydrocortisone is the drug of choice for glucocorticoid replacement in primary adrenal insufficiency because it is the physiologic glucocorticoid with the shortest half-life and allows for twice-daily dosing that mimics the natural cortisol rhythm. ### Rationale for Hydrocortisone **High-Yield:** Hydrocortisone (cortisol) is preferred because: 1. It is the natural glucocorticoid produced by the adrenal cortex 2. Has both glucocorticoid and mineralocorticoid activity (important in primary adrenal insufficiency) 3. Short half-life (~90 minutes) allows physiologic dosing patterns (higher in morning, lower in evening) 4. Typical replacement dose: 15–20 mg/day in divided doses (10 mg morning, 5–10 mg afternoon) 5. Requires concurrent mineralocorticoid replacement (fludrocortisone 0.05–0.2 mg/day) in primary adrenal insufficiency ### Comparison of Glucocorticoids | Drug | Half-life | Mineralocorticoid Activity | Dosing Pattern | Use in Addison | |------|-----------|---------------------------|-----------------|----------------| | Hydrocortisone | ~90 min | Yes (weak) | Twice daily | **First-line** | | Prednisolone | 12–36 hours | No | Once daily | Secondary insufficiency only | | Dexamethasone | 36–72 hours | No | Once daily | Not suitable (too long-acting) | | Methylprednisolone | 12–36 hours | No | Once daily | Not suitable (no mineralocorticoid) | **Clinical Pearl:** In primary adrenal insufficiency (Addison disease), both glucocorticoid AND mineralocorticoid replacement are mandatory. Hydrocortisone provides some mineralocorticoid effect, but fludrocortisone (a synthetic mineralocorticoid) must always be added to manage hyperkalemia and hyponatremia. **Mnemonic:** HYDROcortisone = HYDRo (water/electrolyte balance) — it's the only physiologic steroid with mineralocorticoid activity suitable for Addison disease. ### Stress Dosing During acute illness or surgery, hydrocortisone doses must be increased 2–3 fold to prevent adrenal crisis.