What is the treatment for high Parathyroid Hormone (PTH) levels?

Treatment for High Parathyroid Hormone (PTH) Levels

The treatment for high PTH levels depends on the underlying cause, with primary hyperparathyroidism requiring parathyroidectomy in symptomatic patients, while secondary hyperparathyroidism in chronic kidney disease (CKD) should be managed with vitamin D therapy, phosphate binders, and calcimimetics like cinacalcet, with parathyroidectomy reserved for refractory cases. 1, 2, 3

Diagnosis and Classification

Before initiating treatment, it's essential to determine the type of hyperparathyroidism:

• Primary Hyperparathyroidism (PHPT): Autonomous growth of PTH-producing cells, characterized by high PTH and high calcium levels
• Secondary Hyperparathyroidism (SHPT): Chronic stimulation of parathyroid glands due to low calcium, often seen in CKD
• Tertiary Hyperparathyroidism: Results from prolonged SHPT when glands become autonomous

Treatment Approach Based on Type

Primary Hyperparathyroidism

1. Surgical Management (First-line):

   • Parathyroidectomy is indicated for symptomatic patients 2
   • Two surgical approaches:
     • Bilateral Neck Exploration (BNE)
     • Minimally Invasive Parathyroidectomy (MIP) - offers shorter operating times and faster recovery 2

2. Medical Management (for patients who cannot undergo surgery):

   • Cinacalcet is indicated for treatment of hypercalcemia in patients with primary HPT who cannot undergo parathyroidectomy 3
   • Starting dose: 30 mg twice daily, titrated every 2-4 weeks as needed 3
   • Vitamin D supplementation: High-dose vitamin D (70 μg/2800 IU daily) has been shown to safely decrease PTH by 17% and improve bone mineral density in PHPT patients 4

Secondary Hyperparathyroidism in CKD

Treatment approach based on CKD stage and PTH levels:

1. CKD Not on Dialysis (Stages 3-4):

   • Optimize calcium and vitamin D levels for mildly elevated PTH 2
   • For PTH 300-500 pg/mL: Increase vitamin D sterols and adjust phosphate binders 2
   • For PTH 500-800 pg/mL: Higher doses of vitamin D sterols, consider adding cinacalcet 2
   • Dietary phosphorus restriction to 800-1000 mg/day 2
   • Low-dose active vitamin D can help control PTH when combined with nutritional vitamin D and dietary phosphate restriction 1
   • Ergocalciferol treatment has shown significant PTH reduction (13.1%) in stage 3 CKD but less benefit in stage 4 CKD 5

2. CKD on Dialysis (Stage 5D):

   • Cinacalcet is FDA-approved for SHPT in adult patients with CKD on dialysis 3
   • Starting dose: 30 mg once daily, titrated every 2-4 weeks to target iPTH levels of 150-300 pg/mL 3
   • Target PTH levels for CKD G5D: 150-600 pg/mL 2
   • Novel calcimimetics (etelcalcetide, evocalcet, upacicalcet) have similar or superior efficacy to cinacalcet for PTH reduction 1
   • For PTH >800 pg/mL or refractory to medical therapy: Consider parathyroidectomy 2

3. Parathyroidectomy Options for SHPT:

   • Subtotal Parathyroidectomy (SPTX): Higher recurrence rates due to hyperplasia of residual tissue
   • Total Parathyroidectomy (TPTX): Lower recurrence rates but may cause persistent hypocalcemia
   • Total Parathyroidectomy with Autotransplantation (TPTX+AT): Reduces risk of permanent hypoparathyroidism 2

Monitoring and Follow-up

• Serum calcium and phosphorus: Measure within 1 week of initiation or dose adjustment of cinacalcet 3
• iPTH: Measure 1-4 weeks after initiation or dose adjustment of cinacalcet 3
• Regular monitoring schedule:
  • Secondary HPT with CKD on dialysis: Monthly calcium monitoring 3
  • Primary HPT: Every 2 months calcium monitoring 3
  • Follow-up every 3-6 months initially, then every 6-12 months once stable 2

Important Considerations and Pitfalls

1. Hypocalcemia Risk:

   • Cinacalcet is not indicated for CKD patients not on dialysis due to increased hypocalcemia risk 3
   • If serum calcium falls below 8.4 mg/dL during treatment, increase calcium-containing phosphate binders and/or vitamin D sterols 3
   • If serum calcium falls below 7.5 mg/dL, withhold cinacalcet until levels reach 8 mg/dL 3

2. Post-Kidney Transplantation:

   • Cinacalcet effectively corrects hypercalcemia and hypophosphatemia in persistent hyperparathyroidism after kidney transplantation 1
   • Subtotal parathyroidectomy induces greater reductions of PTH and calcium than cinacalcet and improves bone mineral density 1
   • Consider calcimimetics in the first year post-transplant as reversibility of SHPT may occur 1

3. Switching Between Treatments:

   • When switching from etelcalcetide to cinacalcet, discontinue etelcalcetide for at least 4 weeks and ensure corrected serum calcium is at or above the lower limit of normal before starting cinacalcet 3

By following these evidence-based approaches, PTH levels can be effectively managed while minimizing complications related to calcium and phosphorus metabolism.