What is the treatment for primary hyperparathyroidism with high Parathyroid Hormone (PTH) and hypercalcemia?

Treatment of Primary Hyperparathyroidism with Elevated PTH and Hypercalcemia

Surgery is the only curative treatment for primary hyperparathyroidism, and parathyroidectomy should be performed in patients with hypercalcemia and elevated PTH. 1, 2

Surgical Approach Selection

The choice between two effective surgical strategies depends on preoperative imaging findings and clinical characteristics:

Minimally Invasive Parathyroidectomy (MIP)

• MIP is the preferred approach when preoperative imaging confidently localizes a single parathyroid adenoma (which accounts for 80-85% of primary hyperparathyroidism cases). 1
• This technique offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration. 1, 3
• MIP requires intraoperative PTH monitoring to confirm removal of the hyperfunctioning gland. 1
• Approximately 60% of patients with mild disease (PTH 300-500 pg/mL), 41% with moderate disease (PTH 500-800 pg/mL), and 11% with severe disease (PTH >800 pg/mL) achieve target PTH levels ≤250 pg/mL. 4

Bilateral Neck Exploration (BNE)

• BNE remains necessary when preoperative imaging is discordant, nonlocalizing, or when multigland disease is suspected (occurs in 15-20% of cases). 1
• This approach involves identification and examination of all parathyroid glands by the surgeon, with resection of diseased glands. 1
• BNE is mandatory for hereditary forms of hyperparathyroidism or when thyroid disease requiring surgery coexists. 5

Medical Management for Non-Surgical Candidates

For patients unable to undergo parathyroidectomy despite meeting surgical criteria:

Cinacalcet Therapy

• Start cinacalcet at 30 mg twice daily and 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
• In clinical trials, cinacalcet reduced mean serum calcium by 2.3 mg/dL from baseline (12.7 mg/dL to 10.4 mg/dL) in patients with severe hypercalcemia who could not undergo surgery. 4
• Monitor serum calcium within 1 week after initiation or dose adjustment, then every 2 months once stable. 4

Critical Monitoring Requirements

• Measure serum calcium (corrected for albumin) and intact PTH simultaneously to confirm diagnosis before treatment. 2
• Assess vitamin D status, as deficiency can complicate PTH interpretation and cause secondary hyperparathyroidism. 2
• Be aware that PTH assays vary significantly between laboratories—use assay-specific reference values. 2

Preoperative Imaging Strategy

Preoperative localization imaging is essential for MIP but not required to establish surgical indication. 1

• Negative imaging is not a contraindication for parathyroid surgery. 5
• Common imaging modalities include 99Tc-sestamibi scan, ultrasound, 4-D parathyroid CT (noncontrast, arterial, and venous phases), and MRI. 1
• Selection should consider surgeon and radiologist preference, regional expertise, and patient characteristics. 1

Reoperative Cases

For persistent or recurrent hyperparathyroidism, preoperative imaging with 99Tc-Sestamibi, ultrasound, CT, or MRI is mandatory prior to re-exploration. 1, 3

• Persistent disease is defined as failure to achieve normocalcemia within 6 months of initial surgery. 1
• Recurrent disease occurs after a normocalcemic interval of 6 months or more post-surgery. 1
• Reoperations have lower cure rates and higher complication rates than first-time surgery, making precise localization critical. 1

Common Pitfalls to Avoid

• Do not use imaging to confirm or exclude the diagnosis of primary hyperparathyroidism—diagnosis is biochemical only. 1
• Do not perform total parathyroidectomy in patients who may subsequently receive kidney transplant, as calcium control becomes problematic. 1, 3
• Do not proceed with MIP if imaging shows multigland disease or is nonlocalizing—use BNE instead. 1
• When using cinacalcet, monitor for hypocalcemia and QT interval prolongation. 2, 4