What is the management of primary hyperparathyroidism?

Management of Primary Hyperparathyroidism

Parathyroidectomy is the definitive treatment for primary hyperparathyroidism and should be performed in all symptomatic patients and considered for most asymptomatic patients, as it is more cost-effective than observation or pharmacologic therapy. 1

Initial Diagnostic Evaluation

Before determining management strategy, complete the following workup:

• Confirm diagnosis biochemically by measuring serum calcium (corrected for albumin) and intact PTH simultaneously 2
• Measure 25-hydroxyvitamin D levels, as vitamin D deficiency can complicate PTH interpretation and cause secondary hyperparathyroidism 2, 1
• Obtain 24-hour urine calcium measurement to assess renal calcium handling 1
• Perform dual-energy x-ray absorptiometry (DEXA) to evaluate bone mineral density 1
• Supplement vitamin D deficiency before proceeding with treatment decisions 1

Surgical Management (First-Line Treatment)

Indications for Surgery

Surgery is indicated for: 1, 3

• All symptomatic patients (kidney stones, bone pain, fractures, neuromuscular symptoms, neurocognitive disorders) 4, 1
• Asymptomatic patients with:
  • Serum calcium >1 mg/dL above upper normal limit 5
  • Age <50 years 5
  • Impaired kidney function (GFR <60 mL/min/1.73 m²) 2
  • Osteoporosis on DEXA scan 2
  • Hypercalciuria 2

Preoperative Imaging

Obtain cervical ultrasonography or other high-resolution imaging (sestamibi scan or 4D-CT) for operative planning, particularly to guide minimally invasive approaches 4, 6, 1. Patients with nonlocalizing imaging remain surgical candidates and require bilateral neck exploration 4, 1.

Surgical Approach Selection

Two accepted operative strategies exist: 4, 7

• Minimally invasive parathyroidectomy (MIP): Preferred when a single adenoma is confidently localized preoperatively 6, 7

  • Requires intraoperative PTH monitoring to confirm removal of hyperfunctioning gland 6, 7
  • Offers shorter operating times, faster recovery, and decreased perioperative costs 7
  • Appropriate for approximately 80% of patients with single adenomas 4

• Bilateral neck exploration (BNE): Required for 4, 7

  • Discordant or nonlocalizing preoperative imaging
  • Suspected multigland disease (15-20% of cases) 4
  • Patients with PTH ≤50 pg/mL (58.9% have multigland disease) 6

Important caveat: Preoperative parathyroid biopsy should be avoided 1. Surgeons who perform high-volume operations have better outcomes 1.

Medical Management (For Non-Surgical Candidates Only)

Medical therapy is reserved exclusively for patients who cannot or refuse to undergo surgery 8, 9. The FDA specifically approves cinacalcet for "patients with primary HPT for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy" 8.

Pharmacologic Options

For hypercalcemia control: 9

• Cinacalcet is the treatment of choice to lower serum calcium 9
  • Starting dose: 30 mg twice daily 8
  • 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) 8
  • Reduces serum calcium to normal in many cases but has only modest effect on PTH levels 9
  • Does not improve bone mineral density 9
  • Monitor serum calcium within 1 week after initiation or dose adjustment 8

For bone mineral density improvement: 9

• Alendronate (bisphosphonate therapy) is recommended 9
  • Improves BMD at lumbar spine without altering serum calcium 9
  • Best evidence supports alendronate specifically 9

Combination therapy with both cinacalcet and bisphosphonates is reasonable to address both hypercalcemia and bone loss, though strong evidence for this approach is lacking 9.

Conservative Management Guidelines

For asymptomatic patients >50 years with serum calcium <1 mg/dL above upper normal limit and no skeletal or kidney disease, observation may be appropriate 5. This requires:

• Monitoring symptoms, serum calcium, and creatinine levels regularly 3
• Serial bone mineral density measurements 3
• Maintaining adequate hydration 10
• Moderate dietary calcium intake (500-800 mg/day, not restricted) 9, 10
• Vitamin D repletion to achieve 25-hydroxyvitamin D ≥50 nmol/L (20 ng/mL) minimum, with goal of ≥75 nmol/L (30 ng/mL) 9
• Avoiding immobilization 10
• Using diuretics with caution 10

Critical pitfall: Do not restrict calcium intake in patients with primary hyperparathyroidism who do not undergo surgery, as this can worsen bone disease 9.

Postoperative Management

After parathyroidectomy: 7

• Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 7
• Initiate calcium gluconate infusion if needed 7
• Adjust phosphate binders based on serum phosphorus 7
• Follow up to assess for cure (defined as eucalcemia at >6 months) 1
• Calcium supplementation may be indicated postoperatively 1

Special Considerations

Avoid total parathyroidectomy in patients who may subsequently receive kidney transplant, as control of serum calcium levels may be problematic 7. For reoperative cases, obtain preoperative imaging (sestamibi, ultrasound, CT, or MRI) to localize target lesions and identify postoperative changes 7.