Management of Hyperparathyroidism
Distinguish the Type of Hyperparathyroidism First
The management of hyperparathyroidism depends entirely on whether you are dealing with primary, secondary, or tertiary disease, which is determined by measuring serum calcium, phosphorus, and intact PTH levels. 1, 2
Diagnostic Algorithm:
- Elevated PTH + Hypercalcemia + Low-normal phosphorus = Primary hyperparathyroidism 1, 3
- Elevated PTH + Normal/low calcium + Elevated phosphorus = Secondary hyperparathyroidism (typically CKD-related) 4, 1
- Elevated PTH + Hypercalcemia + History of CKD = Tertiary hyperparathyroidism 5, 6
Management of Primary Hyperparathyroidism
Parathyroidectomy is the definitive treatment for primary hyperparathyroidism and should be performed in patients meeting surgical criteria. 2, 3
Indications for Parathyroidectomy:
- Age ≤50 years 2
- Serum calcium >1 mg/dL above upper limit of normal 2, 3
- Creatinine clearance <60 mL/min/1.73 m² 2
- Presence of osteoporosis 2
- Nephrolithiasis or nephrocalcinosis 2
- Hypercalciuria 2
- Symptomatic hypercalcemia 3
Medical Management (for non-surgical candidates):
- Observation is appropriate for patients >50 years with calcium <1 mg/dL above normal and no skeletal or renal involvement 3
- Cinacalcet 30 mg twice daily, titrated every 2-4 weeks to normalize calcium 7
- Bisphosphonates for bone protection in patients with osteoporosis 8
Management of Secondary Hyperparathyroidism (CKD-Related)
Control hyperphosphatemia first before initiating any vitamin D therapy, as uncontrolled phosphorus dramatically increases vascular calcification risk. 4, 1
Step 1: Control Phosphorus (FIRST PRIORITY)
- Target serum phosphorus 3.5-5.5 mg/dL for CKD stage 5/dialysis patients 4
- Dietary phosphorus restriction to 800-1,000 mg/day 4
- Initiate phosphate binders (non-calcium based preferred if hypercalcemia present) 9, 4, 1
- Do NOT use calcium-based phosphate binders if hypercalcemia exists 4, 1
- Monitor phosphorus monthly after initiating therapy 4
Step 2: Address Hypocalcemia
- Supplemental calcium carbonate 1-2 g three times daily with meals (serves dual purpose as phosphate binder and calcium supplement) 4
- Monitor calcium within 1 week of initiating therapy 4
Step 3: Vitamin D Therapy (ONLY after phosphorus controlled)
- Do NOT initiate active vitamin D therapy until serum phosphorus <4.6 mg/dL 4, 1
- Critical pitfall: Starting vitamin D with uncontrolled hyperphosphatemia worsens vascular calcification 4, 1
- For hemodialysis patients: intermittent IV calcitriol or paricalcitol is more effective than oral administration 4, 10
- Adjust dosage according to severity of hyperparathyroidism 4
Step 4: Target PTH Levels
- Target PTH 150-300 pg/mL for CKD stage 5/dialysis patients (NOT normal range) 4, 1
- Critical pitfall: Targeting normal PTH levels (<100 pg/mL) causes adynamic bone disease with increased fracture risk 4, 1
- For CKD G3a-G5 not on dialysis: evaluate progressively rising PTH above upper normal limit for modifiable factors 9
- Monitor PTH every 3 months once stable 4
Step 5: Calcimimetics (if PTH remains elevated despite optimized vitamin D)
- Cinacalcet 30 mg once daily, titrated every 2-4 weeks to maximum 180 mg daily 7
- Target iPTH 150-300 pg/mL 7
- Contraindicated if serum calcium <8.4 mg/dL 7
- Alternative calcimimetics: etelcalcetide, evocalcet, or upacicalcet 4
- Monitor calcium within 1 week and PTH 1-4 weeks after initiation or dose adjustment 7
Step 6: Dialysate Calcium Adjustment
- Standard dialysate calcium: 2.5 mEq/L (1.25 mmol/L) 9, 1
- For severe hypercalcemia: lower dialysate calcium to 1.5-2.0 mEq/L temporarily 1
- KDIGO recommends dialysate calcium between 1.25-1.50 mmol/L (2.5-3.0 mEq/L) 9
Step 7: Parathyroidectomy Consideration
- Indicated if PTH persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 4
- Reassess after 3-6 months of optimized medical therapy 4
- Parathyroidectomy is associated with lower mortality than calcimimetics and more substantial increase in bone mineral density 4
Surgical Options for Secondary Hyperparathyroidism:
- Total parathyroidectomy (TPTX) has lower recurrence rates (OR 0.17) compared to TPTX with autotransplantation 4
- TPTX offers shorter operative time (17.3 minutes less) 4
- TPTX has higher risk of hypoparathyroidism (OR 2.97) but no permanent hypocalcemia or adynamic bone disease reported 4
Post-Parathyroidectomy Monitoring:
- Monitor ionized calcium every 4-6 hours for first 48-72 hours 4
- Then twice daily until stable 4
- Hypocalcemia is common and managed with calcium and vitamin D supplementation 4
Management of Tertiary Hyperparathyroidism
Tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism after renal transplant) requires parathyroidectomy if medical therapy fails. 11, 5, 6
Medical Management:
- Discontinue calcium-based phosphate binders 1
- Avoid vitamin D supplementation 11
- Trial of cinacalcet if calcium not severely elevated 7
Surgical Management:
- Parathyroidectomy indicated for persistent hypercalcemia despite optimized medical therapy 11, 5
- Surgical options: total parathyroidectomy with/without autotransplantation, subtotal parathyroidectomy 5
- Remove superior parts of thymus during surgery 5
Management of Acute Severe Hypercalcemia (Total Calcium ≥12 mg/dL)
Initiate aggressive IV crystalloid hydration with normal saline as first-line therapy for moderate to severe hypercalcemia. 1, 3
Acute Management Protocol:
- IV normal saline for volume repletion and calciuresis 1, 3
- Loop diuretics (furosemide) ONLY after adequate volume repletion 1, 3
- IV bisphosphonates (zoledronic acid or pamidronate) for PTH-independent hypercalcemia 1, 3
- Calcitonin as temporizing measure for rapid calcium reduction while awaiting bisphosphonate effect 1
- For total calcium ≥14 mg/dL or ionized calcium ≥10 mg/dL: add hypertonic 3% saline 1
Critical Monitoring Parameters
For CKD Patients on Dialysis:
- Calcium and phosphorus monthly for first 3 months, then every 3 months 4
- PTH every 3 months 4
- Alkaline phosphatase annually or more frequently if PTH elevated 9
For CKD Patients NOT on Dialysis:
- CKD G3a-G3b: Calcium/phosphorus every 6-12 months; PTH once then as needed 9
- CKD G4: Calcium/phosphorus every 3-6 months; PTH every 6-12 months 9
- CKD G5: Calcium/phosphorus every 1-3 months; PTH every 3-6 months 9
Post-Kidney Transplant:
- Measure calcium and phosphorus at least weekly until stable in immediate post-transplant period 9
Key Pitfalls to Avoid
- Never start vitamin D therapy with uncontrolled hyperphosphatemia (>4.6 mg/dL) - this dramatically increases vascular calcification 4, 1
- Never target normal PTH levels in dialysis patients - PTH <100 pg/mL causes adynamic bone disease 4, 1
- Never initiate cinacalcet if serum calcium <8.4 mg/dL - contraindicated due to hypocalcemia risk 7
- Cinacalcet is NOT indicated for CKD patients not on dialysis due to increased hypocalcemia risk 7
- Never use calcium-based phosphate binders when hypercalcemia is present 4, 1