What is the management for a patient with hyperparathyroidism (elevated Parathyroid Hormone (PTH)) and hypercalcemia?

Management of Hyperparathyroidism with Hypercalcemia

For a patient with hyperparathyroidism and hypercalcemia (calcium 11 mg/dL), surgical parathyroidectomy is the definitive treatment with the best outcomes for morbidity, mortality, and quality of life. 1

Initial Assessment and Diagnosis

• Determine the type of hyperparathyroidism:

  • Primary hyperparathyroidism (PHPT): Elevated or inappropriately normal PTH with hypercalcemia
  • Secondary hyperparathyroidism: Elevated PTH due to another cause (typically chronic kidney disease)
  • Tertiary hyperparathyroidism: Autonomous PTH secretion after longstanding secondary hyperparathyroidism

• Check additional laboratory values:

  • 25-hydroxyvitamin D (target >20 ng/mL, ideally >30 ng/mL) 1
  • Serum phosphorus
  • Renal function (eGFR)
  • 24-hour urinary calcium excretion
  • Bone mineral density

Treatment Algorithm

1. Primary Hyperparathyroidism with Hypercalcemia

Surgical Management (First-line)

• Parathyroidectomy is the definitive treatment for primary hyperparathyroidism 1, 2

• Indications for surgery:

  • Serum calcium >1 mg/dL above upper limit of normal
  • Hypercalcemia with symptoms (fatigue, constipation, nausea, confusion)
  • Evidence of kidney disease (stones, nephrocalcinosis)
  • Reduced bone mineral density (T-score <-2.5 at any site)
  • Age <50 years
  • 24-hour urinary calcium >400 mg/day

• Preoperative localization:

  • 4D-CT neck without and with IV contrast is the first-line imaging modality 1

Medical Management (If surgery is contraindicated or refused)

1. Cinacalcet:

   • Indicated for hypercalcemia in primary HPT when parathyroidectomy is not possible 3
   • Starting dose: 30 mg twice daily
   • Titrate every 2-4 weeks to maximum 90 mg four times daily as needed 3
   • Monitor serum calcium within 1 week after initiation or dose adjustment 3

2. Bisphosphonates:

   • Effective for improving bone mineral density 4
   • Does not significantly lower serum calcium or PTH levels 4

3. Vitamin D Supplementation:

   • Target 25-OH vitamin D levels >20 ng/mL (50 nmol/L) 1
   • Correct vitamin D deficiency before other treatments

2. Secondary Hyperparathyroidism with Hypercalcemia

For Patients on Dialysis

• Cinacalcet is indicated for secondary hyperparathyroidism in patients with CKD on dialysis 3
  • Starting dose: 30 mg once daily
  • Titrate every 2-4 weeks through sequential doses of 30,60,90,120, and 180 mg once daily
  • Target iPTH levels: 150-300 pg/mL 3

For Patients Not on Dialysis

• Cinacalcet is not indicated due to increased risk of hypocalcemia 3
• Management options:
  1. Correct vitamin D deficiency
  2. Reduce phosphate intake and use phosphate binders
  3. Active vitamin D analogs (calcitriol)

3. Tertiary Hyperparathyroidism

• Parathyroidectomy should be considered for persistent hypercalcemic hyperparathyroidism despite optimized medical therapy 5, 1

Monitoring and Follow-up

• Serum calcium: Check within 1 week after initiation or dose adjustment of cinacalcet 3
• After stabilization:
  • Primary HPT: Check calcium every 2 months 3
  • Secondary HPT: Check calcium, phosphorus, and PTH every 1-3 months based on CKD stage 1

Management of Severe Hypercalcemia (>14 mg/dL)

1. Aggressive IV hydration with normal saline
2. IV bisphosphonates (zoledronic acid or pamidronate) 2
3. Consider hemodialysis for patients with renal failure 2

Pitfalls and Caveats

• Cinacalcet should be used with caution due to risk of hypocalcemia and increased QT interval 5
• Overtreatment of secondary hyperparathyroidism can lead to adynamic bone disease 1
• Normocalcemic hyperparathyroidism (normal total calcium but elevated ionized calcium) may still require treatment 6
• Patients on cinacalcet should take it with food or shortly after a meal 3
• Discontinue etelcalcetide for at least 4 weeks before starting cinacalcet 3

Special Considerations

• For patients with mild asymptomatic primary hyperparathyroidism who are >50 years with serum calcium <1 mg/dL above upper limit and no evidence of skeletal or kidney disease, observation may be appropriate 2
• Medical management is a promising option for those who are not candidates for parathyroidectomy, but surgery remains the definitive treatment with the best outcomes 4