What are the treatment options for a patient with hyperparathyroidism?

Treatment Options for Hyperparathyroidism

Parathyroidectomy is the definitive curative treatment for primary hyperparathyroidism and should be pursued even in asymptomatic patients, while secondary hyperparathyroidism requires initial medical management with surgery reserved for refractory cases. 1, 2

Primary Hyperparathyroidism

Surgical Management - The Definitive Approach

Parathyroidectomy is indicated for all patients with primary hyperparathyroidism, including those who are asymptomatic, given the potential long-term complications of persistent hypercalcemia. 1, 2 The cure rate approaches 99% when performed by experienced surgeons. 3

Surgical Technique Selection:

• Minimally invasive parathyroidectomy (MIP) is the preferred approach when preoperative imaging (99Tc-Sestamibi scan, ultrasound, or 4D-CT) confidently localizes a single adenoma, offering shorter operating times, faster recovery, and decreased costs compared to bilateral neck exploration. 1, 2

• MIP requires intraoperative PTH monitoring to confirm removal of the hyperfunctioning gland and is appropriate for approximately 80% of patients. 2

• Bilateral neck exploration (BNE) is necessary when imaging is discordant, nonlocalizing, or when multigland disease is suspected—particularly important when PTH ≤50 pg/mL, as 58.9% of these patients have multigland disease. 2

Postoperative Monitoring:

• Check ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable. 1, 2
• Initiate calcium gluconate infusion if hypocalcemia develops and adjust phosphate binders based on serum phosphorus levels. 2

Medical Management - Limited Role

Medical therapy with cinacalcet is indicated only for patients with primary hyperparathyroidism who cannot undergo parathyroidectomy due to surgical contraindications. 4

• Starting dose: 30 mg twice daily orally with food. 4
• Titrate every 2-4 weeks through sequential doses (30 mg twice daily → 60 mg twice daily → 90 mg twice daily → 90 mg 3-4 times daily) to normalize serum calcium. 4
• Monitor serum calcium within 1 week of initiation or dose adjustment, then every 2 months once stable. 4

Important caveat: Bisphosphonates and hormone replacement therapy may help manage bone density but do not cure the underlying disease. 5

Secondary Hyperparathyroidism

Initial Medical Management - First-Line Approach

All patients with secondary hyperparathyroidism should begin with comprehensive medical therapy before considering surgery. 6, 2

Step 1: Dietary and Phosphate Management

• Dietary phosphorus restriction as the foundation. 6
• Phosphate-binding agents to control hyperphosphatemia. 6

Step 2: Calcium and Vitamin D Correction

• Correct hypocalcemia with calcium supplementation. 2
• Vitamin D sterols (calcitriol, paricalcitol, or doxercalciferol) with dosage adjusted according to hyperparathyroidism severity. 2
  • For peritoneal dialysis patients: oral calcitriol 0.5-1.0 μg or doxercalciferol 2.5-5.0 μg given 2-3 times weekly. 2
  • Monitor serum calcium and phosphorus every 2 weeks for 1 month after initiation or dose increase, then monthly. 1, 2
  • Monitor PTH monthly for at least 3 months, then every 3 months once target levels achieved. 2

Step 3: Calcimimetics for Persistent Disease

• Cinacalcet (30 mg once daily) is indicated for secondary hyperparathyroidism in adult patients with CKD on dialysis when medical management with vitamin D and phosphate binders is insufficient. 4
• Critical limitation: Cinacalcet is NOT indicated for CKD patients not on dialysis due to increased hypocalcemia risk. 4
• Titrate every 2-4 weeks through sequential doses (30 → 60 → 90 → 120 → 180 mg once daily) to target iPTH levels of 150-300 pg/mL. 4
• Monitor serum calcium within 1 week of initiation/dose adjustment, then monthly once stable. 1, 4
• Measure iPTH 1-4 weeks after initiation or dose adjustment, no earlier than 12 hours after dosing. 4

Surgical Management - For Refractory Cases

Parathyroidectomy is recommended when medical therapy fails and specific criteria are met. 6, 2

Absolute Indications for Surgery:

• Persistent serum intact PTH >800 pg/mL associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy. 2, 7
• Refractory and/or symptomatic hypercalcemia after excluding other causes. 6
• Refractory hyperphosphatemia despite optimal medical management. 6
• Severe intractable pruritus that becomes debilitating. 6, 1
• Serum calcium × phosphorus product persistently exceeding 70-80 mg²/dL² with progressive extraskeletal calcifications. 6, 7
• Calciphylaxis. 6
• Severe bone disease with pathological fractures and skeletal deformities when PTH exceeds 10 times the upper normal limit. 1, 7

Surgical Options:

Three approaches have shown excellent results: 6, 2

• Subtotal parathyroidectomy
• Total parathyroidectomy with parathyroid tissue autotransplantation
• Total parathyroidectomy without autotransplantation

Critical caveat: Total parathyroidectomy without autotransplantation is NOT recommended for patients who may subsequently receive a kidney transplant, as control of serum calcium levels may be problematic. 2

Special Populations

Renal Transplant Candidates and Recipients

• Measure calcium, phosphorus, and PTH as part of pretransplant evaluation and repeat periodically while on the transplant waiting list. 6
• Almost 90% of renal transplant recipients have elevated PTH at transplantation, and more than 30% persist with elevated PTH up to 3 years post-transplant. 6
• Successful renal transplantation is the best treatment for most causes of low-turnover bone disease and dialysis-related amyloid bone disease. 6
• Duration on dialysis and intensity of pretransplant hyperparathyroidism correlate with severity of post-transplant hyperparathyroidism. 6

Parathyroid Carcinoma

• Cinacalcet is indicated for hypercalcemia in parathyroid carcinoma when surgery is not feasible. 4
• Starting dose: 30 mg twice daily, titrated as for primary hyperparathyroidism. 4
• Monitor serum calcium every 2 months once stable. 4

Common Pitfalls to Avoid

• Do not use cinacalcet in CKD patients not on dialysis—the hypocalcemia risk outweighs benefits. 4
• Do not delay parathyroidectomy in asymptomatic primary hyperparathyroidism—long-term hypercalcemia causes progressive organ damage. 1, 2
• Do not perform total parathyroidectomy without autotransplantation in potential kidney transplant candidates—calcium management becomes extremely difficult. 2
• Do not rely solely on PTH levels for surgical decision-making in primary hyperparathyroidism—the presence of hypercalcemia and target organ damage are more important. 6
• Ensure vitamin D repletion before attributing elevated PTH to primary disease—vitamin D deficiency causes secondary hyperparathyroidism and is extremely common, particularly in elderly patients. 6, 5