A 38-year-old woman with severe rheumatoid arthritis is started on prednisolone 20 mg daily for 6 weeks. Regarding the adverse effects of prolonged corticosteroid therapy, all of the following are recognized complications EXCEPT:

Explanation

## Adverse Effects of Prolonged Corticosteroid Therapy ### Recognized Complications (Options 0, 1, 2) **Option 0: Osteoporosis** - Glucocorticoids cause bone loss through multiple mechanisms: 1. **Decreased osteoblast function** — reduced bone formation 2. **Increased osteoclast activity** — enhanced bone resorption 3. Reduced intestinal calcium absorption (decreased 1,25-dihydroxyvitamin D) 4. Increased urinary calcium excretion - Prednisolone ≥7.5 mg/day for >3 months significantly increases fracture risk - This is a major complication of long-term corticosteroid use [cite:Harrison Ch 377] **Option 1: Hypokalemia and metabolic alkalosis** - Even glucocorticoids have weak mineralocorticoid activity - Prednisolone at 20 mg/day has sufficient mineralocorticoid effect to cause: - Sodium retention and potassium excretion - Hypokalemia (K⁺ <3.5 mEq/L) - Metabolic alkalosis (from H⁺ loss in collecting duct) - More pronounced with synthetic glucocorticoids like dexamethasone - Requires monitoring and potassium supplementation [cite:KD Tripathi Ch 57] **Option 2: Increased infection risk** - Glucocorticoids suppress cell-mediated immunity (T-cell function) - Prednisolone 20 mg/day is immunosuppressive - Increased risk of: - Opportunistic infections: *Pneumocystis jirovecii*, *Mycobacterium tuberculosis*, *Candida*, *Cryptococcus* - Viral reactivation: CMV, varicella-zoster - Atypical presentations (masked symptoms, delayed immune response) - PCP prophylaxis recommended if CD4 <200 or prolonged high-dose steroids [cite:Park 26e Ch 6] ### Incorrect Statement (Option 3: Hypercalcemia) **Key Point:** Prolonged corticosteroid therapy causes **HYPOcalcemia and hypercalciuria, NOT hypercalcemia.** **Mechanism of calcium loss:** 1. **Decreased intestinal calcium absorption** — glucocorticoids inhibit 1α-hydroxylase, reducing conversion of 25-OH vitamin D to active 1,25-dihydroxyvitamin D 2. **Increased urinary calcium excretion** — direct effect on renal tubules 3. **Reduced bone formation** — osteoblasts are suppressed 4. **Net result:** Negative calcium balance, hypocalcemia, and secondary hyperparathyroidism **Hypercalcemia occurs in:** - Hyperthyroidism - Vitamin D intoxication - Sarcoidosis (extrarenal 1α-hydroxylase) - Lymphomas (PTHrP secretion) - Immobilization - ~~Corticosteroid therapy~~ (this is the opposite) **High-Yield:** This is a classic NEET PG trap question. Candidates often confuse the mechanism: corticosteroids cause bone loss → hypocalcemia → secondary hyperparathyroidism. The hypercalciuria is a consequence of the negative calcium balance, not a cause of hypercalcemia. **Clinical Pearl:** Patients on prolonged corticosteroids require calcium and vitamin D supplementation, and DEXA scanning for osteoporosis screening [cite:Harrison Ch 377]. ## Corticosteroid Adverse Effects Summary Table | System | Adverse Effect | Mechanism | Onset | | --- | --- | --- | --- | | **Bone** | Osteoporosis | ↓ Osteoblasts, ↑ osteoclasts | Weeks–months | | **Electrolytes** | Hypokalemia, alkalosis | Mineralocorticoid effect | Days–weeks | | **Immune** | Infections (PCP, TB, fungal) | ↓ T-cell immunity | Weeks–months | | **Calcium** | HYPOcalcemia, hypercalciuria | ↓ Intestinal absorption, ↑ renal loss | Weeks–months | | **Metabolic** | Hyperglycemia, dyslipidemia | ↑ Gluconeogenesis, ↑ lipolysis | Days–weeks | | **CNS** | Psychosis, insomnia, mood changes | Direct CNS effects | Days–weeks | | **GI** | Peptic ulcer disease | ↑ Acid secretion, ↓ mucus | Weeks–months |