What is the treatment approach for primary hyperparathyroidism?

Treatment Approach for Primary Hyperparathyroidism

Parathyroidectomy is the definitive treatment for primary hyperparathyroidism (PHPT), with surgical excision of pathological parathyroid tissue being curative in 95-98% of cases. 1 For patients who cannot undergo surgery, medical management options are available.

Surgical Management

Indications for Surgery

• All patients with PHPT should be considered for parathyroidectomy as it is the only definitive therapy 2
• Specific indications include:
  • Symptomatic hypercalcemia
  • Serum calcium >1 mg/dL above normal range
  • Osteoporosis or pathological fractures
  • Nephrolithiasis or nephrocalcinosis
  • Age <50 years

Surgical Approaches

• Bilateral cervical exploration by an experienced parathyroid surgeon (95-98% success rate) 3
• Minimally invasive parathyroidectomy when a single adenoma is adequately localized preoperatively
• Intraoperative PTH measurement helps confirm complete removal of abnormal tissue

Medical Management

For patients unable to undergo parathyroidectomy, the following options are available:

Cinacalcet

• First-line medical therapy for hypercalcemia in PHPT patients who cannot undergo surgery 4
• FDA-approved for treatment of hypercalcemia in PHPT patients for whom parathyroidectomy would be indicated but who are unable to undergo the procedure 4
• Dosing:
  • Starting dose: 30 mg twice daily
  • Titrate every 2-4 weeks through sequential doses (30 mg twice daily, 60 mg twice daily, 90 mg twice daily, and 90 mg 3-4 times daily) as needed to normalize serum calcium 4
  • Monitor serum calcium within 1 week after initiation or dose adjustment 4
• Effectively reduces serum calcium but has modest effect on PTH levels and does not improve bone mineral density 2

Bisphosphonates

• Recommended to improve bone mineral density in PHPT patients 2
• Alendronate has the strongest evidence, improving BMD at the lumbar spine without altering serum calcium 2

Combination Therapy

• Combined cinacalcet and bisphosphonate therapy may be reasonable to both reduce serum calcium and improve BMD 2

Calcium and Vitamin D Management

• Do not restrict calcium intake in PHPT patients who don't undergo surgery 2
• Follow standard calcium intake guidelines for all individuals 2
• Replete vitamin D deficiency to achieve serum 25-hydroxyvitamin D levels ≥50 nmol/L (20 ng/mL), with a goal of ≥75 nmol/L (30 ng/mL) being reasonable 2

Monitoring

• After establishing maintenance dose, monitor serum calcium every 2 months for patients with PHPT 4
• If serum calcium falls below 8.4 mg/dL, adjust treatment accordingly 4
• Regular assessment of renal function and bone mineral density is recommended

Non-Surgical Ablative Techniques

• Consider in patients with absolute contraindications to surgery:
  • Selective percutaneous ethanol injection
  • Transcatheter ablation of pathological parathyroid tissue 3

Common Pitfalls and Caveats

• Misdiagnosis is common as PHPT can present with vague symptoms affecting multiple organ systems 5
• Low serum albumin and acid-base disturbances can affect serum calcium levels and complicate perioperative management 6
• Ectopic parathyroid glands (particularly in the mediastinum) are associated with increased risk of surgical failure 1
• Severe hypercalcemia can lead to neurological symptoms, cardiac arrhythmias, and renal dysfunction requiring urgent intervention 6, 5

For patients with PHPT who have contraindications to surgery or refuse surgical intervention, a structured approach using cinacalcet for hypercalcemia control and bisphosphonates for bone protection offers the best medical management strategy.