What is the management plan for tertiary hyperparathyroidism?

Management of Tertiary Hyperparathyroidism

Surgery is the primary treatment for tertiary hyperparathyroidism, with total parathyroidectomy with autotransplantation (TPTX+AT) being the most commonly recommended approach. 1

Definition and Pathophysiology

• Tertiary hyperparathyroidism most commonly occurs following kidney transplantation in patients with long-standing chronic kidney disease, when hypertrophied parathyroid tissue fails to resolve and continues to oversecrete PTH despite normal or elevated serum calcium levels 1, 2
• It can also develop after long-term oral phosphate therapy in conditions such as familial hypophosphatemic rickets 3

Diagnostic Evaluation

• Diagnosis is based on elevated PTH levels with hypercalcemia or normocalcemia, particularly in patients with a history of secondary hyperparathyroidism 2
• Imaging is essential for surgical planning and should identify all eutopic and potential ectopic or supernumerary glands 1
• Multiphase CT (4D-CT) is valuable for localizing parathyroid tissue, leveraging the unique perfusion characteristics of parathyroid glands 1
• Ultrasound and dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT are also highly sensitive for localizing parathyroid adenomas 4

Medical Management

• Medical therapy may be attempted first, particularly in patients who are poor surgical candidates 5
• For patients with X-linked hypophosphatemia and tertiary hyperparathyroidism, careful management of phosphate supplements and active vitamin D is crucial 1
• Calcimimetics such as cinacalcet may be used to control hypercalcemia, with 80.8% of patients achieving normocalcemia, though 6.4% discontinue treatment due to side effects 6
• Ensure adequate vitamin D levels (>20 ng/ml) and appropriate calcium intake 4

Surgical Management

• Surgery is the definitive treatment for persistent hypercalcemic hyperparathyroidism that is refractory to medical therapy 1, 5

• Three main surgical approaches are available 2, 7:

  1. Total parathyroidectomy with autotransplantation (TPTX+AT)
  2. Subtotal parathyroidectomy (SPTX)
  3. Total parathyroidectomy without autotransplantation (TPTX)

• TPTX+AT is the most commonly recommended approach for several reasons 1:

  • Prevents permanent hypoparathyroidism
  • Allows regulation of PTH levels by adjusting the autotransplanted tissue
  • Provides easier access to recurrent disease in the autograft site versus reoperation in the neck

• Surgical cure rates are significantly higher than medical therapy (98.7-100% vs. 80.8%) 6

• It is important to remove superior parts of the thymus as well, as ectopic parathyroid tissue may be present 2

Post-Surgical Management

• Close monitoring of calcium levels is essential post-surgery 1, 4, 5:
  • Monitor ionized calcium every 4-6 hours for the first 48-72 hours
  • Provide calcium supplementation if hypocalcemia develops
  • Initiate calcium gluconate infusion for severe hypocalcemia
  • Transition to oral calcium carbonate and calcitriol when oral intake is possible

Outcomes and Follow-up

• Recurrence rates after subtotal and total parathyroidectomy are 7.6% and 4% respectively 6
• Persistent or recurrent tertiary hyperparathyroidism is more common in patients who had initial limited (1- or 2-gland) parathyroidectomy instead of subtotal or total parathyroidectomy with autotransplantation 7
• Long-term follow-up is critical, with careful dosage adjustments in phosphate and vitamin D therapy and monitoring of serum levels of phosphorus, calcium, and parathyroid hormone 3

Alternative Approaches

• For recurrent disease after parathyroidectomy, percutaneous embolization has been reported as an alternative treatment option, though experience is limited 8

Common Pitfalls and Caveats

• Preoperative localizing studies may fail to identify ectopic or supernumerary glands, necessitating bilateral neck exploration 7
• Limited parathyroidectomy (removal of only 1-2 glands) has a significantly higher risk of persistent or recurrent disease and should be avoided 7
• Tertiary hyperparathyroidism is usually due to multiple hyperplastic parathyroid glands (4-gland hyperplasia in 97% of cases), not single adenomas, making bilateral neck exploration necessary 7