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

Treatment for High Parathyroid Hormone (PTH) Levels

Treatment for high PTH levels should be tailored to the specific type of hyperparathyroidism (primary, secondary, or tertiary) and underlying cause, with surgical intervention being the definitive treatment for primary hyperparathyroidism and medical management focusing on correcting underlying abnormalities in secondary hyperparathyroidism. 1

Types of Hyperparathyroidism and Diagnostic Approach

Different types of hyperparathyroidism require different treatment approaches:

1. Primary Hyperparathyroidism:

   • Characterized by elevated or inappropriately normal PTH with hypercalcemia
   • Usually caused by parathyroid adenoma (80%) or multigland hyperplasia (15-20%)
   • Diagnosis: Elevated serum calcium with elevated/normal PTH, elevated urinary calcium 1, 2

2. Secondary Hyperparathyroidism:

   • Compensatory PTH elevation due to hypocalcemia, most commonly in chronic kidney disease (CKD)
   • Characterized by elevated PTH with normal/low serum calcium and low urinary calcium
   • Diagnosis: Elevated PTH, normal/low calcium, elevated phosphate (in CKD) 1

3. Tertiary Hyperparathyroidism:

   • Autonomous PTH secretion after longstanding secondary hyperparathyroidism
   • Often occurs after kidney transplantation
   • Diagnosis: Elevated PTH with hypercalcemia 3, 4

Treatment Algorithm for High PTH

1. Primary Hyperparathyroidism Treatment

• First-line treatment: Parathyroidectomy (surgical removal of abnormal parathyroid tissue) 1, 2
• For patients unable to undergo surgery: Cinacalcet tablets starting at 30 mg twice daily, titrated every 2-4 weeks as needed to normalize calcium levels 5
• Monitor serum calcium every 2 months after maintenance dose established 5

2. Secondary Hyperparathyroidism Treatment (CKD-related)

For CKD patients on dialysis:

1. Initial therapy: Cinacalcet tablets 30 mg once daily with food 5

   • Titrate dose every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily
   • Target iPTH levels: 150-600 pg/mL (2-9× upper normal limit) 1, 5

2. Combination therapy:

   • Cinacalcet can be used with vitamin D sterols and/or phosphate binders 5
   • Control calcium-phosphate imbalances to prevent vascular calcification 1

3. Monitoring:

   • Check serum calcium and phosphorus within 1 week of starting/adjusting cinacalcet
   • Check iPTH 1-4 weeks after dose adjustments
   • Monthly calcium monitoring once maintenance dose established 5

For CKD patients not on dialysis:

• Cinacalcet is contraindicated due to increased hypocalcemia risk 5
• Target PTH levels based on CKD stage:
  • CKD G3: <70 pg/mL
  • CKD G4: <110 pg/mL
  • CKD G5 (non-dialysis): <300 pg/mL 1

Stepwise approach based on PTH level:

• Mildly elevated: Optimize calcium and vitamin D levels
• 300-500 pg/mL: Increase vitamin D sterols, adjust phosphate binders
• 500-800 pg/mL: Higher doses of vitamin D sterols, consider adding cinacalcet
• >800 pg/mL: Consider parathyroidectomy if medical therapy fails 1

3. Tertiary Hyperparathyroidism Treatment

• Primary treatment: Surgical parathyroidectomy (total, subtotal, or limited) 3
• Include removal of superior parts of thymus during surgery 3

Management of Underlying Factors

1. Correct vitamin D deficiency with nutritional supplements 1
2. Control phosphate levels:
   • Restrict dietary phosphate intake
   • Use phosphate binders to target normal phosphate levels 1
3. Maintain serum calcium within normal range (8.4-9.5 mg/dL in CKD) 1
4. Address metabolic acidosis (maintain serum total CO2 >22 mEq/L) 1
5. For dialysis patients:
   • Optimize dialysis adequacy
   • Maintain dialysate calcium between 1.25-1.50 mmol/L 1

Important Considerations and Pitfalls

• Hypocalcemia risk with cinacalcet: If calcium falls below 8.4 mg/dL but remains above 7.5 mg/dL, increase calcium-containing phosphate binders and/or vitamin D sterols 5
• Severe hypocalcemia: If calcium falls below 7.5 mg/dL, withhold cinacalcet until levels reach 8 mg/dL 5
• Switching medications: When switching from etelcalcetide to cinacalcet, discontinue etelcalcetide for at least 4 weeks and ensure corrected calcium is at/above lower limit of normal 5
• Referral indications:
  • CKD patients with GFR < 45 mL/min/1.73m² should be referred to nephrology
  • Patients with decompensated liver disease, suspected malignancy, or metabolic bone disease should be referred to appropriate specialists 1

Special Populations

• Pediatric patients: Primary hyperparathyroidism is rare but requires surgical excision of adenoma when present 6
• Parathyroid carcinoma: Cinacalcet starting at 30 mg twice daily, titrated as needed to normalize calcium levels 5