What is the workup and management for a patient with hyperparathyroidism (high PTH)?

Workup and Management for Hyperparathyroidism (High PTH)

The comprehensive workup for hyperparathyroidism should include serum calcium, phosphorus, vitamin D levels, and assessment of kidney function, followed by appropriate imaging studies if surgical intervention is indicated. The management depends on the type of hyperparathyroidism (primary, secondary, or tertiary) and underlying causes.

Initial Diagnostic Workup

Laboratory Tests

• Serum calcium (total and ionized)
• Serum phosphorus
• Intact PTH level
• 25(OH) vitamin D level
• 1,25(OH)₂ vitamin D level
• Serum creatinine and estimated GFR
• Alkaline phosphatase (ALP) or bone-specific ALP
• 24-hour urinary calcium and creatinine clearance
• Serum albumin (for corrected calcium calculation)

Classification Based on Initial Labs

1. Primary Hyperparathyroidism:

   • Elevated or high-normal serum calcium with elevated or inappropriately normal PTH
   • Low or low-normal phosphorus
   • Normal to high 1,25(OH)₂ vitamin D

2. Secondary Hyperparathyroidism:

   • Normal or low serum calcium
   • Elevated phosphorus (especially in CKD)
   • Elevated PTH
   • Low 25(OH) vitamin D and/or 1,25(OH)₂ vitamin D

3. Tertiary Hyperparathyroidism:

   • Elevated serum calcium
   • Elevated PTH
   • History of long-standing secondary hyperparathyroidism (usually post-kidney transplant) 1

Management by Type of Hyperparathyroidism

Primary Hyperparathyroidism

1. Surgical Management:

   • Parathyroidectomy is indicated for:
     • Symptomatic patients
     • Serum calcium >0.25 mmol/L above upper limit of normal
     • Age <50 years
     • Osteoporosis or fragility fractures
     • Kidney stones or nephrocalcinosis
     • eGFR <60 mL/min/1.73m²

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

   • Cinacalcet is indicated for hypercalcemia in patients with primary HPT who are unable to undergo parathyroidectomy 2
   • Initial dose: 30 mg twice daily, titrated every 2-4 weeks as needed
   • Monitor serum calcium every 2 months after establishing maintenance dose 2

Secondary Hyperparathyroidism in CKD

1. For CKD Stages G3a-G5 (not on dialysis):

   • Evaluate for modifiable factors if PTH is progressively rising or persistently above normal:
     • Hyperphosphatemia
     • Hypocalcemia
     • High phosphate intake
     • Vitamin D deficiency 3
   • Phosphate restriction and phosphate binders for hyperphosphatemia
   • Calcitriol or vitamin D analogs are not routinely recommended but may be used for severe progressive hyperparathyroidism in CKD G4-G5 3

2. For CKD Stage G5D (on dialysis):

   • Target PTH range: 2-9 times the upper normal limit for the assay 3
   • Treatment options:
     • Calcimimetics (cinacalcet)
     • Calcitriol or vitamin D analogs
     • Combination therapy 3
   • Initial dose of cinacalcet: 30 mg once daily with titration every 2-4 weeks 2
   • Monitor serum calcium, phosphorus, and PTH regularly

3. Management of elevated PTH in patients on conventional treatment:

   • Increase dose of active vitamin D and/or decrease dose of oral phosphate supplements 3
   • Consider calcimimetics for persistent secondary hyperparathyroidism 3
   • Parathyroidectomy for tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism) despite optimized therapy 3

Tertiary Hyperparathyroidism

• Typically occurs after kidney transplantation in patients with long-standing secondary hyperparathyroidism 1, 4
• Characterized by autonomous PTH secretion and hypercalcemia
• Treatment options:
  • Medical management with cinacalcet
  • Parathyroidectomy (total, subtotal, or limited) 1

Imaging Studies (When Surgical Management is Indicated)

• Sestamibi scan
• Ultrasound of neck
• CT scan or MRI of neck
• 4D-CT scan (when available)

Monitoring

• For CKD patients:

  • Monitor serum calcium and phosphorus every 3-6 months in CKD G4, every 1-3 months in CKD G5
  • Monitor PTH every 6-12 months in CKD G4, every 3-6 months in CKD G5 3
  • Measure alkaline phosphatase annually or more frequently with elevated PTH

• For post-parathyroidectomy patients:

  • Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 3
  • Calcium supplementation as needed to maintain normal calcium levels

Special Considerations

• Intraoperative PTH monitoring during parathyroidectomy can help predict successful surgery 5
• Rare cases of primary hyperparathyroidism may present with hypercalcemia and low-normal PTH levels 6
• Parathyroidectomy should be considered for renal transplant candidates with severe hyperparathyroidism that has failed medical management 3

Complications to Monitor

• Hypercalcemia: cardiac arrhythmias, kidney stones, dehydration
• Bone disease: osteoporosis, fractures, bone pain
• Nephrocalcinosis and kidney stones
• Post-parathyroidectomy hypocalcemia (can be severe)

Remember that the goal of treatment is to normalize calcium and PTH levels while minimizing complications related to bone disease, kidney disease, and cardiovascular risk.