What are the diagnosis and treatment options for primary hyperparathyroidism?

Primary Hyperparathyroidism: Diagnosis and Treatment

Surgical parathyroidectomy is the definitive treatment for primary hyperparathyroidism (PHPT), resulting in long-term cure in >95% of cases and should be considered for all patients with symptomatic disease or those meeting surgical criteria. 1

Diagnosis

Laboratory Testing

• Initial diagnosis requires biochemical testing:
  • Elevated serum calcium (total or ionized)
  • Elevated or inappropriately normal parathyroid hormone (PTH) levels
  • Rule out conditions that mimic PHPT

Imaging Studies

• Imaging is used for localization prior to surgery, not for diagnosis
• Recommended imaging modalities (ACR Appropriateness Criteria) 1:
  • First-line: Ultrasound of the neck and 99mTc-sestamibi scintigraphy
  • Second-line: 4D-CT or MRI when first-line studies are negative or discordant

Etiology and Presentation

• Most cases (80%) are due to a single parathyroid adenoma
• 15-20% from multigland disease (multiple adenomas or hyperplasia)
• <1% from parathyroid carcinoma
• More common in women (66 per 100,000 person-years vs 25 in men) 1

Clinical Presentation

• In countries with routine biochemical screening: often asymptomatic
• In countries without routine screening: symptomatic with:
  • Bone demineralization and fractures
  • Nephrolithiasis/nephrocalcinosis
  • Muscle weakness
  • Neurocognitive disorders

Treatment Options

1. Surgical Management

• Surgical approaches 1, 2:

  • Bilateral Neck Exploration (BNE): Traditional approach examining all parathyroid glands
  • Minimally Invasive Parathyroidectomy (MIP): Targeted removal of affected gland with limited dissection
    • Advantages: shorter operating time, faster recovery, decreased costs

• Indications for surgery 2, 3:

  • All symptomatic patients (kidney stones, bone disease, neurocognitive symptoms)
  • Asymptomatic patients meeting any criteria:
    • Serum calcium >1 mg/dL above upper limit of normal
    • Osteoporosis or fragility fracture
    • Age <50 years
    • Creatinine clearance <60 mL/min
    • Nephrolithiasis or nephrocalcinosis
    • Hypercalciuria >400 mg/day

• Surgical outcomes 4:

  • Normalization of serum calcium
  • Significant increase in bone mineral density (8% at lumbar spine after 1 year, 12% after 10 years)
  • Prevention of recurrent kidney stones

2. Medical Management

For patients who cannot or decline surgery:

• Calcium and vitamin D management 2, 3:

  • Follow normal calcium intake guidelines (do not restrict)
  • Replete vitamin D if deficient to ≥50 nmol/L (20 ng/mL), preferably to ≥75 nmol/L (30 ng/mL)

• Pharmacological options 5, 3:

  • For hypercalcemia control: Cinacalcet

    • Starting dose: 30 mg once daily
    • Titrate every 2-4 weeks as needed
    • Effectively reduces serum calcium but has modest effect on PTH and no effect on BMD

  • For bone protection: Bisphosphonates (alendronate)

    • Improves BMD at lumbar spine without affecting serum calcium

  • For both hypercalcemia and BMD concerns: Consider combination therapy with cinacalcet and bisphosphonate

Monitoring

For Surgically Treated Patients

• Measure serum calcium within 1 week post-surgery
• Follow-up at 6 months and then annually if stable

For Medically Managed Patients 2, 6

• Monitor serum calcium, phosphorus, and PTH every 3-6 months initially
• Once stable, monitor every 6-12 months
• Bone mineral density testing every 1-2 years
• Renal imaging if history of kidney stones

Special Considerations

Elderly Patients

• Medical management may be appropriate for elderly patients (>85 years) 7
• Most medically managed elderly patients show long-term stability of disease

Pitfalls to Avoid

• Don't restrict calcium intake in PHPT patients not undergoing surgery
• Don't use cinacalcet in patients with CKD who are not on dialysis due to hypocalcemia risk 5
• Don't rely on imaging for diagnosis - it's only for localization before surgery
• Don't miss the opportunity for surgical cure in symptomatic patients or those meeting criteria

Treatment Algorithm

1. Confirm diagnosis with elevated calcium and elevated/inappropriately normal PTH
2. Evaluate for surgical indications
3. If surgical candidate: Refer to experienced parathyroid surgeon
4. If not surgical candidate:
   • Maintain normal calcium intake
   • Correct vitamin D deficiency
   • Consider cinacalcet for hypercalcemia
   • Consider bisphosphonates for bone protection
   • Monitor regularly for disease progression

Surgical parathyroidectomy remains the gold standard treatment with excellent outcomes for symptom resolution and prevention of complications.