What are the guidelines for diagnosing and treating hyperparathyroidism?

Guidelines for Diagnosing and Treating Hyperparathyroidism

Surgical excision (parathyroidectomy) is the definitive treatment for primary hyperparathyroidism, offering the best outcomes for morbidity, mortality, and quality of life. 1

Diagnosis of Hyperparathyroidism

Laboratory Evaluation

• Measure serum calcium, phosphorus, PTH, and 25-hydroxyvitamin D levels
• Check 25(OH) vitamin D levels before initiating treatment (target >30 ng/mL) 1
• For preoperative localization in primary hyperparathyroidism, 4D-CT neck without and with IV contrast is recommended (sensitivity 79%, PPV 90% for single gland disease) 1

Classification of Hyperparathyroidism

1. Primary Hyperparathyroidism

   • Characterized by hypercalcemia with inappropriately elevated PTH
   • Most commonly caused by parathyroid adenoma

2. Secondary Hyperparathyroidism

   • Appropriate PTH elevation in response to a stimulus (commonly low serum calcium)
   • Normal serum calcium with elevated PTH 2
   • Common in chronic kidney disease (CKD)

3. Tertiary Hyperparathyroidism

   • Excessive PTH secretion after longstanding secondary hyperparathyroidism
   • Characterized by hypercalcemia
   • Typically occurs in patients with chronic kidney disease, especially after kidney transplant 2, 3

Treatment Guidelines

Primary Hyperparathyroidism

• First-line treatment: Parathyroidectomy for symptomatic patients or those meeting surgical criteria 1, 4
• Medical management (for those who cannot undergo surgery):
  • Bisphosphonates: Effective for decreasing bone turnover and improving bone mineral density 5
  • Hormone replacement therapy: Can improve bone mineral density but does not significantly lower calcium or PTH 5
  • Cinacalcet: Indicated for hypercalcemia in primary HPT when parathyroidectomy is not possible 6

Secondary Hyperparathyroidism in CKD

Treatment Approach Based on PTH Levels:

• Mildly elevated PTH: Optimize calcium and vitamin D levels
• PTH 150-300 pg/mL: Maintain current therapy
• PTH 300-500 pg/mL: Increase vitamin D sterols, adjust phosphate binders
• PTH 500-800 pg/mL: Higher doses of vitamin D sterols, consider adding cinacalcet
• PTH >800 pg/mL: Consider parathyroidectomy if medical therapy fails 1

Medication Options:

1. Active Vitamin D Analogs:

   • Paricalcitol: Indicated for prevention and treatment of secondary hyperparathyroidism in CKD stages 3-5 7
     • Initial dosing:
       • CKD 3-4: 1 mcg daily or 2 mcg three times weekly (if baseline iPTH ≤500 pg/mL)
       • CKD 5: Dose (mcg) = baseline iPTH (pg/mL) divided by 80, administered three times weekly 7

2. Calcimimetics:

   • Cinacalcet: Indicated for secondary hyperparathyroidism in adult CKD patients on dialysis 6
   • Should be used with caution due to risk of hypocalcemia 8, 1
   • Not indicated for CKD patients who are not on dialysis 6

3. Phosphate Binders:

   • Non-calcium-based phosphate binders may be preferred in patients with elevated calcium-phosphate product 1
   • Recommended progressive increase in phosphate supplements for insufficient response, but avoid doses >80mg/kg daily to prevent gastrointestinal discomfort and hyperparathyroidism 8

Tertiary Hyperparathyroidism

• First-line treatment: Parathyroidectomy 3
• Surgical options:
  • Total parathyroidectomy with or without autotransplantation
  • Subtotal parathyroidectomy
  • Limited parathyroidectomy 3
• Consider parathyroidectomy in cases of persistent hypercalcemic hyperparathyroidism despite optimized active vitamin D and cinacalcet therapy 8

Monitoring Guidelines

• Monitor serum calcium, phosphorus, and PTH levels every 3 months (more frequently in advanced CKD) 1
• Monitoring frequency based on CKD stage:
  • Stage 3: Every 6-12 months
  • Stage 4: Every 3-6 months
  • Stage 5: Every 1-3 months
  • Dialysis: Monthly 1

Common Pitfalls and Complications

• Hypercalcemia: If serum calcium exceeds 10.5 mg/dL, discontinue active vitamin D therapy immediately 1
• Nephrocalcinosis: Keep urinary calcium levels within normal range, ensure regular water intake, consider potassium citrate, and limit sodium intake 8, 1
• Overtreatment: Avoid aggressive PTH-lowering therapy in patients with PTH levels at the lower end of target range 1
• Hungry bone syndrome: Common post-parathyroidectomy complication (up to 36.2% of cases) 1
• Adynamic bone disease: Risk with calcitriol, especially in patients with low PTH levels 1

By following these guidelines for diagnosis and treatment of hyperparathyroidism, clinicians can optimize patient outcomes while minimizing complications associated with both the disease and its treatment.