A 38-year-old woman with systemic lupus erythematosus (SLE) presents with acute lupus nephritis (Class IV). She is started on high-dose intravenous methylprednisolone 1 g daily for 3 days, followed by oral prednisolone 1 mg/kg/day. After 2 weeks of therapy, she develops severe hypokalemia (K⁺ 2.8 mEq/L), hypertension (160/100 mmHg), and hyperglycemia (fasting glucose 280 mg/dL). Which of the following best explains the mechanism underlying these adverse effects?

Explanation

## Mechanism of Corticosteroid-Induced Metabolic Complications **Key Point:** Glucocorticoids, especially at high doses, possess inherent mineralocorticoid activity that increases renal sodium reabsorption and potassium excretion in the distal tubule. ### Mineralocorticoid Effects Methylprednisolone and other glucocorticoids bind to mineralocorticoid receptors (MR) in the collecting duct, leading to: 1. Increased Na⁺ reabsorption via epithelial sodium channels (ENaC) 2. Enhanced K⁺ secretion and H⁺ secretion 3. Fluid retention → hypertension 4. Hypokalemic metabolic alkalosis **High-Yield:** The mineralocorticoid potency varies: **dexamethasone and betamethasone** (minimal MR activity) < **prednisolone and methylprednisolone** (moderate MR activity) < **hydrocortisone and cortisone** (high MR activity). ### Hyperglycemia Mechanism Glucocorticoids induce hyperglycemia via: - Increased hepatic gluconeogenesis (↑ PEPCK, G6Pase) - Decreased peripheral glucose utilization (insulin resistance) - Reduced pancreatic insulin secretion (direct beta-cell suppression) - Lipolysis → increased free fatty acids → impaired glucose uptake **Clinical Pearl:** Hypokalemia from corticosteroids is **NOT** due to increased GFR (which would dilute electrolytes, not cause selective K⁺ loss) or catecholamine excess (which causes hyperkalemia, not hypokalemia). ### Table: Mineralocorticoid Potency of Common Corticosteroids | Corticosteroid | Glucocorticoid Potency | Mineralocorticoid Potency | MR Activity | | --- | --- | --- | --- | | Hydrocortisone | 1 | 1 | High | | Prednisolone | 4 | 0.8 | Moderate | | Methylprednisolone | 5 | 0.5 | Moderate | | Dexamethasone | 25 | 0 | Minimal | | Betamethasone | 25 | 0 | Minimal | **Tip:** When high-dose glucocorticoids cause hypokalemia + hypertension, suspect mineralocorticoid activity. Consider switching to dexamethasone (if equivalent anti-inflammatory effect is needed) or adding a potassium-sparing diuretic (spironolactone). [cite:KD Tripathi 8e Ch 57]