What is the best treatment approach for primary hyperparathyroidism?

Treatment of Primary Hyperparathyroidism

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

Surgical Indications

Surgery is indicated for:

• All symptomatic patients with signs of hypercalcemia, bone disease, or nephrolithiasis 1
• Asymptomatic patients meeting any of the following criteria: 1
  • Age younger than 50 years
  • Significant hypercalcemia
  • Impaired renal function
  • Renal stones or nephrocalcinosis 2
  • Osteoporosis on dual-energy x-ray absorptiometry 1

Surgical Approaches

Two effective surgical options exist, both achieving high cure rates (>95% in experienced centers): 1, 3

Minimally Invasive Parathyroidectomy (MIP)

• Requires confident preoperative localization of a single parathyroid adenoma 4
• Intraoperative PTH monitoring via a reliable protocol is mandatory 4, 1
• Offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration 4
• Not recommended for known or suspected multigland disease 1

Bilateral Neck Exploration (BNE)

• Remains the standard approach when preoperative imaging is negative or shows discordant/nonlocalizing results 4, 5
• Essential for suspected multigland disease, which should be routinely considered 1
• Allows identification of all parathyroid glands 5

Preoperative Evaluation and Imaging

Initial workup must include: 1

• 25-hydroxyvitamin D measurement
• 24-hour urine calcium measurement
• Dual-energy x-ray absorptiometry
• Vitamin D supplementation if deficient

Preoperative imaging for operative planning: 2

• Cervical ultrasonography or other high-resolution imaging is recommended 1
• No single imaging technique is clearly superior; selection should consider surgeon/radiologist preference, regional expertise, and patient characteristics 2
• Multiple imaging modalities may be combined to maximize accuracy through concordant results 2
• Patients with nonlocalizing imaging remain surgical candidates 1
• Preoperative parathyroid biopsy should be avoided 1

Common imaging modalities include: 2

• 4-D parathyroid CT (multiphase CT without and with IV contrast)
• Tc99m-sestamibi scintigraphy with SPECT/CT
• Ultrasound

Medical Management (Non-Surgical Candidates Only)

Medical management may be considered only in patients with mild asymptomatic disease who have contraindications to surgery or who refuse surgery: 6, 1

Cinacalcet (Calcimimetic Agent)

• FDA-approved for hypercalcemia in adult patients with primary hyperparathyroidism for whom parathyroidectomy would be indicated on the basis of serum calcium levels, but who are unable to undergo parathyroidectomy 7
• Starting dose: 30 mg twice daily, titrated every 2-4 weeks through sequential doses up to 90 mg 3-4 times daily as necessary to normalize serum calcium 7
• Effectively lowers serum calcium and PTH levels 6
• Serum calcium should be measured within 1 week after initiation or dose adjustment 7
• Common adverse effects include nausea (63%), vomiting (46%), and hypocalcemia 7

General Medical Measures

• Optimize calcium intake to 500-800 mg/day (moderate intake, not restriction) 8
• Optimize vitamin D status 6, 1
• Maintain adequate hydration 8
• Avoid immobilization 8
• Use diuretics only with caution 8

Skeletal Protection

• Antiresorptive therapy (bisphosphonates) may be used for skeletal protection in patients with increased fracture risk 6
• Note: Effect on fracture risk reduction is unknown and requires further research 6

Important Caveats

Surgeon volume matters: Surgeons who perform a high volume of parathyroid operations have better outcomes 1

Reoperative cases require special consideration: 2

• Preoperative imaging is essential to localize target lesions and identify postoperative changes 2, 4
• Lower cure rates and higher complication rates than first-time surgery 2

Postoperative management: 1

• Monitor for hematoma
• Evaluate for hypocalcemia and symptoms
• Calcium supplementation may be indicated 1
• Follow-up to assess cure (eucalcemia at >6 months) 1
• Devascularized normal parathyroid tissue should be autotransplanted 1

Medical management is NOT a substitute for surgery in appropriate surgical candidates - it is reserved only for those unable or unwilling to undergo parathyroidectomy. 6, 1