What is the management of primary hyperparathyroidism and hypercalcemia?

Management of Primary Hyperparathyroidism and Hypercalcemia

Parathyroidectomy is the definitive treatment for primary hyperparathyroidism (PHPT) with end-organ complications or severe hypercalcemia, while medical management is appropriate for those who cannot undergo surgery. 1

Diagnosis and Assessment

• Measure serum concentrations of:

  • Intact parathyroid hormone (iPTH)
  • Calcium (total and ionized)
  • Albumin (for corrected calcium calculation)
  • Phosphorus
  • Magnesium
  • 25-hydroxyvitamin D
  • 1,25-dihydroxyvitamin D

• Primary hyperparathyroidism is characterized by:

  • Elevated iPTH levels
  • Elevated or high-normal serum calcium
  • Low or normal phosphorus
  • Elevated 1,25-dihydroxyvitamin D levels 2

Management Algorithm

1. Severe Hypercalcemia (>14.0 mg/dL or symptomatic)

Immediate management:

1. IV crystalloid fluid rehydration (normal saline without calcium)

   • Corrects dehydration and increases renal calcium excretion
   • First-line treatment for acute management 2, 3

2. Loop diuretics (e.g., furosemide)

   • Only after adequate volume repletion
   • Note: Recent evidence suggests limited additional benefit over saline hydration alone 3

3. Bisphosphonates

   • Zoledronic acid is most potent and effective (normalizes calcium in ~60% of cases) 3
   • Consider in moderate to severe hypercalcemia
   • Takes 2-4 days for full effect

4. Cinacalcet

   • Drug of choice for controlling hypercalcemia in PHPT 4, 5
   • Starting dose: 30 mg twice daily
   • Titrate every 2-4 weeks as needed (max: 90 mg four times daily)
   • Reduces serum calcium effectively but has modest effect on PTH levels 5

5. Denosumab

   • Consider when bisphosphonates are contraindicated (renal insufficiency)
   • Effective as bridge therapy to surgery 6, 7
   • Useful in cases refractory to conventional treatment 7

6. Calcitonin

   • For immediate short-term management
   • Effect wanes after 48-72 hours due to tachyphylaxis 8

2. Non-Severe Hypercalcemia

Surgical Candidates:

• Parathyroidectomy is indicated for:
  • Serum calcium >1 mg/dL above upper limit of normal
  • End-organ complications (kidney stones, osteoporosis)
  • Age <50 years
  • Creatinine clearance <60 mL/min 1

Non-Surgical Candidates:

• Cinacalcet

  • First-line medical therapy for hypercalcemia control
  • Starting dose: 30 mg twice daily
  • Titrate every 2-4 weeks based on serum calcium levels 4, 5

• Bisphosphonates (e.g., alendronate)

  • Recommended to improve bone mineral density (BMD)
  • Does not significantly alter serum calcium 5

• Combination therapy

  • Consider cinacalcet + bisphosphonate when both hypercalcemia control and BMD improvement are needed 5

• Calcium and vitamin D management

  • Do not restrict calcium intake
  • Replete vitamin D if deficient (target ≥50 nmol/L or 20 ng/mL)
  • Higher target of ≥75 nmol/L (30 ng/mL) is reasonable 5

Monitoring

• Serum calcium: Check within 1 week after initiation or dose adjustment of cinacalcet 4
• Maintenance monitoring:
  • Every 2 months for PHPT patients on medical therapy 4
  • Monitor for hypocalcemia, especially when initiating therapy

Common Pitfalls and Caveats

1. Avoid furosemide before adequate hydration - Can worsen dehydration and hypercalcemia

2. Beware of hypocalcemia with bisphosphonates or denosumab - Monitor calcium levels closely

3. Don't restrict dietary calcium - Follow general calcium intake guidelines for all individuals 5

4. Watch for drug interactions with cinacalcet - Metabolized by CYP3A4; adjust dose with strong inhibitors/inducers

5. Consider combination therapy - Cinacalcet controls calcium but doesn't improve BMD; bisphosphonates improve BMD but don't significantly lower calcium 5

6. Recognize limitations of medical therapy - Surgery remains definitive treatment; medical therapy is for those who cannot or choose not to undergo surgery