How is secondary hyperparathyroidism managed?

Management of Secondary Hyperparathyroidism

Secondary hyperparathyroidism should be managed with a combination of vitamin D sterols, phosphate control, calcium management, and in severe cases, calcimimetics or surgical intervention, with treatment adjusted according to PTH severity and underlying cause.

Pathophysiology and Approach

Secondary hyperparathyroidism (SHPT) commonly develops in chronic kidney disease (CKD) due to:

• Reduced plasma levels of 1,25(OH)2D leading to decreased intestinal calcium absorption and impaired suppression of PTH synthesis 1
• Phosphate retention 2
• Calcium imbalance 2

Management Algorithm Based on Etiology

For CKD-Related Secondary Hyperparathyroidism:

1. Control Serum Phosphorus

   • Dietary phosphorus restriction 1, 2
   • Phosphate binders (calcium-based or non-calcium based) 1, 3
   • Target serum phosphorus within normal range 1

2. Vitamin D Therapy

   • For hemodialysis patients: Intermittent intravenous calcitriol (1-3 μg, 3 times weekly) or paricalcitol (2-5 μg, 3 times weekly) 1
   • For peritoneal dialysis patients: Oral calcitriol (0.5-1.0 μg) or doxercalciferol (2.5-5.0 μg) 2-3 times weekly 1
   • Intravenous administration is more effective than oral for suppressing PTH levels 1

3. Dose Adjustment Based on PTH Levels

   • Adjust vitamin D sterol dosage according to severity of hyperparathyroidism 1
   • For PTH >500-600 pg/mL: Higher doses of vitamin D sterols required 1
   • For PTH >1,000 pg/mL: Larger doses and longer treatment periods (>12-24 weeks) may be needed 1

4. Calcimimetics (Cinacalcet)

   • Starting dose: 30 mg once daily with food 4
   • Titrate every 2-4 weeks through sequential doses (30,60,90,120,180 mg once daily) 4
   • Target iPTH levels: 150-300 pg/mL 4
   • Monitor serum calcium frequently during dose titration 4
   • Consider for persistent SHPT despite vitamin D therapy 1

5. Monitoring Parameters

   • Serum calcium and phosphorus: Every 2 weeks for 1 month after initiating or adjusting vitamin D therapy, then monthly 1
   • PTH: Monthly for at least 3 months, then every 3 months once target levels achieved 1

For Non-CKD Related Secondary Hyperparathyroidism:

1. Calcium Supplementation

   • For insufficient calcium intake: Oral calcium 600 mg twice daily 5
   • Can normalize PTH levels within 2-3 weeks in patients with normal kidney function and vitamin D levels 5

2. Native Vitamin D Supplementation

   • Supplement with cholecalciferol or ergocalciferol in case of vitamin D deficiency 1, 6
   • Native vitamin D supplementation plays a preventive role in SHPT 6

Management of Complications

Secondary Hyperparathyroidism in X-linked Hypophosphatemia:

• Increase dose of active vitamin D and/or decrease dose of oral phosphate supplements 1
• Avoid phosphate doses >80 mg/kg daily to prevent hyperparathyroidism 1
• Consider calcimimetics for persistent SHPT despite above measures 1

Hypercalcemia Management:

• If serum calcium rises above normal range, reduce or temporarily discontinue vitamin D therapy 1
• Adjust phosphate binders if needed 1

Hypocalcemia Management:

• If serum calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL: Increase calcium-containing phosphate binders and/or vitamin D sterols 4
• If serum calcium falls below 7.5 mg/dL: Withhold cinacalcet until serum calcium reaches 8 mg/dL, then restart at lower dose 4

Surgical Management

Parathyroidectomy should be considered in:

1. Severe hyperparathyroidism with hypercalcemia that precludes medical therapy 1
2. Severe hyperphosphatemia that precludes medical therapy 1
3. Tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism) despite optimized active vitamin D and cinacalcet therapy 1
4. Calciphylaxis with elevated PTH levels (>500 pg/mL) 1

Surgical Options:

• Total parathyroidectomy (TPTX) 1
• Total parathyroidectomy with autotransplantation (TPTX+AT) 1
• Subtotal parathyroidectomy (SPTX) 1

Post-Parathyroidectomy Care:

• Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 1
• If ionized calcium falls below normal, initiate calcium gluconate infusion (1-2 mg elemental calcium per kg body weight per hour) 1
• When oral intake is possible, administer calcium carbonate 1-2 g three times daily and calcitriol up to 2 μg/day 1

Common Pitfalls and Caveats

• Overtreatment with vitamin D sterols can lead to hypercalcemia and hyperphosphatemia, increasing risk of vascular calcification 2
• Inadequate phosphate control can worsen SHPT despite vitamin D therapy 3
• Delayed recognition of tertiary hyperparathyroidism requiring surgical intervention 1
• Cinacalcet should be used with caution as it can cause severe hypocalcemia and increased QT interval 1
• Not all patients with calciphylaxis have high PTH levels; parathyroidectomy should not be performed without documented hyperparathyroidism 1