What are the management options for hyperparathyroidism?

Management of Hyperparathyroidism

Parathyroidectomy should be performed in patients with severe hyperparathyroidism (persistent serum levels of intact PTH >800 pg/mL) associated with hypercalcemia and/or hyperphosphatemia that are refractory to medical therapy. 1

Types of Hyperparathyroidism and Initial Management

Primary Hyperparathyroidism

• First-line treatment: Parathyroidectomy for symptomatic patients or those meeting surgical criteria
• Medical management (for those unable to undergo surgery):
  • Cinacalcet: Starting dose 30 mg twice daily, titrated every 2-4 weeks through sequential doses (30 mg twice daily → 60 mg twice daily → 90 mg twice daily → 90 mg 3-4 times daily) as needed to normalize calcium levels 2
  • Vitamin D supplementation: For patients with vitamin D deficiency, supplementation with cholecalciferol (2800 IU daily) has been shown to decrease PTH by 17%, increase bone mineral density, and decrease bone resorption markers 3

Secondary Hyperparathyroidism

In Chronic Kidney Disease (CKD) on Dialysis:

1. Cinacalcet therapy:

   • Starting dose: 30 mg once daily
   • Titrate every 2-4 weeks through doses of 30,60,90,120, and 180 mg once daily
   • Target iPTH levels: 150-300 pg/mL 2
   • Monitor serum calcium and phosphorus within 1 week of initiation or dose adjustment
   • Monitor iPTH 1-4 weeks after initiation or dose adjustment

2. Active vitamin D therapy:

   • Calcitriol or analogs (doxercalciferol, alfacalcidol, paricalcitol) to target PTH 150-300 pg/mL 1
   • For intravenous administration: More effective than daily oral calcitriol in lowering PTH levels
   • For peritoneal dialysis: Oral calcitriol (0.5-1.0 μg) or doxercalciferol (2.5-5.0 μg) 2-3 times weekly, or lower dose calcitriol (0.25 μg) daily 1

3. Management of elevated PTH with vitamin D therapy:

   • If calcium levels rise above target: Consider alternative vitamin D analogs (paricalcitol or doxercalciferol)
   • If phosphorus levels rise above target: Adjust phosphate binders and/or reduce vitamin D dose

In X-linked Hypophosphatemia (XLH):

• For patients with elevated PTH levels: Increase dose of active vitamin D and/or decrease dose of oral phosphate supplements 1
• For persistent secondary hyperparathyroidism: Consider calcimimetics (cinacalcet) with caution due to risk of hypocalcemia and increased QT interval 1
• For tertiary hyperparathyroidism: Consider parathyroidectomy if hypercalcemic hyperparathyroidism persists despite optimized active vitamin D and cinacalcet therapy 1

In Non-CKD Patients:

• For secondary hyperparathyroidism with normal kidney function and normal vitamin D levels: Calcium supplementation (600 mg twice daily) has been shown to normalize PTH levels within approximately 18 days 4

Surgical Management

Indications for Parathyroidectomy:

• Severe hyperparathyroidism (PTH >800 pg/mL) with hypercalcemia/hyperphosphatemia refractory to medical therapy 1
• Tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism) despite optimized medical therapy 1

Surgical Options:

• Subtotal parathyroidectomy
• Total parathyroidectomy with parathyroid tissue autotransplantation 1

Pre-surgical Considerations:

• Imaging of parathyroid glands with 99Tc-Sestamibi scan, ultrasound, CT scan, or MRI before re-exploration parathyroid surgery 1
• Treatment plans should be discussed in a multidisciplinary team setting 1

Post-parathyroidectomy Management:

1. Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 1
2. If ionized calcium falls below normal (<0.9 mmol/L):
   • Initiate calcium gluconate infusion at 1-2 mg elemental calcium/kg/hour
   • Adjust to maintain normal ionized calcium (1.15-1.36 mmol/L) 1
3. When oral intake is possible:
   • Calcium carbonate 1-2 g three times daily
   • Calcitriol up to 2 μg/day 1
4. Adjust or discontinue phosphate binders based on serum phosphorus levels 1

Monitoring Recommendations

1. For secondary hyperparathyroidism in CKD on dialysis:

   • Serum calcium: Monthly after maintenance dose established
   • Serum phosphorus: Monthly
   • PTH: Monthly for at least 3 months, then every 3 months once target levels achieved 1

2. For parathyroid carcinoma or primary hyperparathyroidism:

   • Serum calcium: Every 2 months after maintenance dose established 2

3. For patients on cinacalcet:

   • 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
   • If serum calcium falls below 7.5 mg/dL: Withhold cinacalcet until calcium reaches 8 mg/dL, then restart at lower dose 2

Common Pitfalls and Caveats

1. Risk of hypercalcemia with vitamin D therapy: Can promote vascular calcification and coronary artery disease 5, 6

2. Risk of over-suppression of PTH: May lead to adynamic bone disease that cannot buffer excess calcium and phosphate, increasing risk of vascular calcification 5

3. Cinacalcet cautions:

   • Contraindicated if serum calcium is below normal range
   • Can cause hypocalcemia leading to paresthesias, myalgias, muscle spasms, tetany, seizures, QT interval prolongation, and ventricular arrhythmia 2
   • Use with caution in patients with congenital long QT syndrome or other conditions predisposing to QT interval prolongation 2

4. Phosphate supplement cautions: Doses >80 mg/kg daily can cause gastrointestinal discomfort and worsen hyperparathyroidism 1

5. Nephrocalcinosis risk: Keep calciuria levels within normal range and avoid large doses of phosphate supplements; consider measures to decrease urinary calcium concentration (regular water intake, potassium citrate, limited sodium intake) 1