How is secondary hyperparathyroidism managed?

Management of Secondary Hyperparathyroidism

Secondary hyperparathyroidism in CKD patients should be managed with a stepwise approach starting with phosphorus control and dietary restriction, followed by vitamin D therapy only after phosphorus is controlled, then calcimimetics for persistent elevation, and finally parathyroidectomy for severe refractory disease. 1

Step 1: Control Hyperphosphatemia FIRST

Critical: Do not start vitamin D therapy until phosphorus is controlled—this worsens vascular calcification. 1

• Target serum phosphorus between 3.5-5.5 mg/dL for stage 5 CKD patients 1
• Initiate dietary phosphorus restriction to 800-1,000 mg/day (while maintaining adequate protein intake of 1.0-1.2 g/kg/day for dialysis patients) 1
• Add phosphate binders (calcium-based or non-calcium-based) as needed 1
• Monitor serum phosphorus monthly after initiating therapy 1
• Do not initiate active vitamin D therapy until serum phosphorus falls below 4.6 mg/dL 1

Step 2: Address Hypocalcemia

• Provide supplemental calcium carbonate 1-2 g three times daily with meals (serves dual purpose as phosphate binder and calcium supplement) 1
• Monitor calcium levels within 1 week of initiating therapy 1

Step 3: Vitamin D Therapy (Only After Phosphorus Control)

• For hemodialysis patients: Use intermittent intravenous calcitriol or paricalcitol (more effective than oral administration for PTH suppression) 1
• For peritoneal dialysis patients: Oral calcitriol (0.5-1.0 μg) or doxercalciferol (2.5-5.0 μg) given 2-3 times weekly 2
• Target PTH levels of 150-300 pg/mL for stage 5 CKD/dialysis patients—NOT normal range 1
• Adjust dosage according to severity of hyperparathyroidism 1
• Monitor calcium and phosphorus every 2 weeks for 1 month after initiation or dose increase, then monthly 2
• Monitor PTH monthly for at least 3 months, then every 3 months once target achieved 2
• If serum calcium rises above normal range, reduce or temporarily discontinue vitamin D therapy 1

Critical Pitfall: Targeting normal PTH levels (<65 pg/mL) in dialysis patients causes adynamic bone disease with increased fracture risk. 1

Step 4: Calcimimetics for Persistent Elevation

• If PTH remains elevated despite optimized vitamin D therapy, add calcimimetics (cinacalcet, etelcalcetide, evocalcet, or upacicalcet) 1, 2
• Cinacalcet starting dose: 30 mg once daily with food 3
• Measure serum calcium and phosphorus within 1 week, and iPTH 1-4 weeks after initiation 3
• Titrate no more frequently than every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily 3
• Monitor serum calcium monthly once maintenance dose established 3
• Caution: Cinacalcet causes hypocalcemia and QT prolongation—contraindicated if serum calcium is below lower limit of normal 3
• If calcium falls below 8.4 mg/dL but above 7.5 mg/dL: increase calcium-containing phosphate binders and/or vitamin D sterols 3
• If calcium falls below 7.5 mg/dL: withhold cinacalcet until calcium reaches 8 mg/dL, then restart at next lowest dose 3

Step 5: Surgical Management for Refractory Disease

Indications for parathyroidectomy: 1, 2

• PTH persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy
• Reassess after 3-6 months of optimized medical therapy before proceeding 1

Surgical options: 1, 2

• Total parathyroidectomy (TPTX): Lower recurrence rates (OR 0.17) and shorter operative time compared to TPTX with autotransplantation 1
• Total parathyroidectomy with autotransplantation (TPTX+AT): Lower risk of permanent hypoparathyroidism 4
• Subtotal parathyroidectomy (SPTX) 1

Important consideration: Avoid total parathyroidectomy in patients who may subsequently receive kidney transplant, as calcium control becomes problematic 2

Postoperative monitoring: 1, 2

• Monitor ionized calcium every 4-6 hours for first 48-72 hours
• Then twice daily until stable
• Hypocalcemia is common and managed with calcium and vitamin D supplementation 1

Key Monitoring Parameters

• During initial treatment: Calcium and phosphorus every 2 weeks for 1 month, then monthly 2
• PTH monitoring: Monthly for first 3 months, then every 3 months 1
• On calcimimetics: Calcium monthly, PTH every 1-3 months 4, 3

Evidence on Outcomes

• Parathyroidectomy is associated with lower mortality than calcimimetics in observational data and shows more substantial increase in bone mineral density 1
• Novel calcimimetics have similar or superior efficacy to cinacalcet for PTH reduction 1
• Vitamin D analogs enhance survival of CKD patients when used appropriately 5