What is the management and further workup of primary hyperparathyroidism?

Management and Further Workup of Primary Hyperparathyroidism

Parathyroidectomy is the definitive treatment for primary hyperparathyroidism (PHPT) and should be recommended for all symptomatic patients and those meeting surgical criteria, while medical therapy with cinacalcet is indicated for patients unable to undergo surgery. 1

Diagnosis and Initial Evaluation

• Laboratory confirmation:

  • Elevated or inappropriately normal parathyroid hormone (PTH) levels with elevated or high-normal serum calcium
  • Low or normal phosphorus levels
  • Elevated 1,25-dihydroxyvitamin D levels

• Additional workup:

  • 24-hour urine calcium excretion
  • Serum creatinine and estimated GFR
  • 25-hydroxyvitamin D levels
  • Bone mineral density (BMD) testing at lumbar spine, hip, and distal radius
  • Renal imaging if history of kidney stones

Surgical Management

Indications for Parathyroidectomy

Parathyroidectomy should be recommended for patients with:

• Serum calcium >1 mg/dL above upper limit of normal
• End-organ complications (osteoporosis, nephrolithiasis)
• Age <50 years
• Creatinine clearance <60 mL/min 1

Preoperative Localization

• Neck ultrasound and 99mTc-sestamibi scintigraphy are first-line imaging modalities
• 4D-CT or MRI may be considered if initial imaging is negative
• Parathyroid venous sampling may be needed in cases of persistent or recurrent disease

Surgical Approach

• Minimally invasive parathyroidectomy is preferred when a single adenoma is localized
• Bilateral neck exploration may be necessary for multiglandular disease
• Intraoperative PTH monitoring helps confirm successful removal of all hyperfunctioning tissue

Medical Management

For Patients Unable to Undergo Surgery

• Cinacalcet:

  • Drug of choice for controlling hypercalcemia in PHPT
  • Starting dose: 30 mg twice daily
  • Titrate every 2-4 weeks as needed to normalize calcium levels
  • Monitor serum calcium within 1 week after initiation or dose adjustment 2
  • Maintenance monitoring every 2 months 1

• Bisphosphonates:

  • Alendronate is recommended to improve BMD without altering serum calcium
  • Consider for patients with osteoporosis or low bone mass

• Combination therapy:

  • Cinacalcet plus bisphosphonate may be used to both reduce calcium and improve BMD
  • Evidence for this approach is limited 3

Calcium and Vitamin D Management

• Calcium intake should follow general population guidelines (1000-1200 mg/day)
• Do not restrict calcium intake in PHPT patients not undergoing surgery
• Vitamin D repletion is recommended for deficient patients
  • Target 25-hydroxyvitamin D levels ≥50 nmol/L (20 ng/mL), with a goal of ≥75 nmol/L (30 ng/mL) being reasonable 3

Monitoring

• For patients on medical therapy:

  • Serum calcium and PTH every 2-3 months
  • Annual BMD testing
  • Renal imaging every 1-2 years if history of kidney stones

• For post-surgical patients:

  • Serum calcium and PTH at 1 week, 6 months, and annually thereafter
  • Monitor for hypocalcemia in immediate post-operative period

Special Considerations

Normocalcemic PHPT

• Characterized by normal serum calcium but elevated PTH
• Rule out secondary causes of hyperparathyroidism
• Same surgical criteria apply if end-organ damage is present

Asymptomatic PHPT

• Surgery can be considered even in patients who don't meet strict criteria but prefer surgical management 3
• Regular monitoring is essential if conservative management is chosen

Referral Indications

• Endocrinology referral for all patients with confirmed PHPT
• Surgical referral for patients meeting criteria for parathyroidectomy
• Nephrology referral for patients with GFR <45 mL/min/1.73m² 1

Pitfalls and Caveats

• Familial hypocalciuric hypercalcemia can mimic PHPT but does not require surgery
• Vitamin D deficiency can mask hypercalcemia in PHPT
• Normocalcemic PHPT requires exclusion of secondary causes of hyperparathyroidism
• Parathyroidectomy success rates are highly dependent on surgeon experience
• Medical therapy does not cure PHPT but can control manifestations of the disease