What is the initial approach to treating hyperparathyroidism?

Initial Approach to Treating Hyperparathyroidism

Surgery is the only definitive cure for primary hyperparathyroidism, and parathyroidectomy should be performed in all symptomatic patients and considered for most asymptomatic patients. 1, 2

Diagnostic Confirmation and Initial Workup

Before initiating treatment, confirm the diagnosis and assess disease severity:

• Measure serum calcium (corrected for albumin) and intact PTH simultaneously to establish the diagnosis of primary hyperparathyroidism (elevated or inappropriately normal PTH with hypercalcemia) 1, 3
• Check 25-hydroxyvitamin D levels to exclude vitamin D deficiency as a concomitant cause of secondary hyperparathyroidism, targeting levels >20 ng/mL (50 nmol/L) 1, 3, 2
• Obtain 24-hour urine calcium measurement to assess hypercalciuria (>400 mg/24h indicates increased surgical urgency due to renal stone risk) 1, 3, 2
• Perform dual-energy x-ray absorptiometry (DEXA) to evaluate for osteoporosis 2
• Assess renal function with serum creatinine and eGFR, as eGFR <60 mL/min/1.73 m² represents an additional surgical indication 3, 2

Surgical Indications

Parathyroidectomy is indicated for:

• All symptomatic patients (bone disease, nephrolithiasis, neurocognitive symptoms, muscle weakness) 1, 2
• Asymptomatic patients meeting any of these criteria: 1, 3, 2
  • Age ≤50 years
  • Serum calcium >1 mg/dL above upper limit of normal
  • Creatinine clearance <60 mL/min/1.73 m²
  • Osteoporosis (T-score ≤-2.5 at any site)
  • Nephrolithiasis or nephrocalcinosis
  • Hypercalciuria >400 mg/24 hours

Preoperative Imaging

Perform localization imaging to guide surgical approach:

• First-line: Cervical ultrasonography and/or 99mTc-sestamibi scintigraphy with SPECT/CT for identifying parathyroid adenomas 4, 1, 2
• The combination of ultrasound and sestamibi increases localization accuracy 4, 1
• Patients with nonlocalizing imaging remain surgical candidates and should undergo bilateral neck exploration 2
• Never perform preoperative parathyroid biopsy as it risks seeding and is unnecessary 2

Surgical Approach Selection

Two appropriate surgical options exist:

• Minimally invasive parathyroidectomy (MIP) for single adenoma with concordant preoperative imaging, using intraoperative PTH monitoring to confirm adequate resection 1, 2
• Bilateral neck exploration (BNE) for multigland disease, nonlocalizing imaging, or discordant imaging results 4, 1, 2

MIP offers shorter operating times, faster recovery, and decreased costs compared to BNE 1, but MIP is not recommended for known or suspected multigland disease 2

Medical Management (When Surgery Contraindicated or Declined)

For patients who cannot undergo surgery:

• Maintain adequate hydration with fluid intake achieving urine volume ≥2.5 liters daily to prevent stone formation 1, 5
• Avoid thiazide diuretics as they reduce urinary calcium excretion and worsen hypercalcemia 3, 5
• Ensure moderate dietary calcium intake (500-800 mg/day) rather than restriction 5
• Avoid immobilization which worsens hypercalcemia 5
• Consider cinacalcet for hypercalcemia in primary hyperparathyroidism when parathyroidectomy is indicated but patient cannot undergo surgery, starting at 30 mg twice daily and titrating every 2-4 weeks 6

Important caveat: Cinacalcet is not indicated for patients with CKD who are not on dialysis due to increased hypocalcemia risk 6

Secondary Hyperparathyroidism Management

For secondary hyperparathyroidism (typically from CKD or vitamin D deficiency):

• Correct vitamin D deficiency with cholecalciferol or ergocalciferol supplementation 4, 1
• Dietary phosphate restriction and phosphate binders for CKD patients 1
• Correction of hypocalcemia with calcium supplementation 1
• For CKD patients on dialysis with persistent elevation: cinacalcet 30 mg once daily, titrating to target iPTH 150-300 pg/mL 6
• Parathyroidectomy is indicated for tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism despite medical therapy) 4

Post-Surgical Monitoring

After parathyroidectomy:

• Monitor ionized calcium every 4-6 hours for the first 48-72 hours, then twice daily until stable 1, 3
• Initiate calcium gluconate infusion if calcium falls below normal 1, 3
• Provide oral calcium carbonate and calcitriol when oral intake is possible 1, 3
• Assess for cure with eucalcemia at >6 months post-operatively 2

Critical Pitfalls to Avoid

• Do not delay surgery in patients with recurrent renal stones and hyperparathyroidism, as this leads to progressive renal damage 1
• Do not use sodium citrate instead of potassium citrate for stone prevention, as it increases urinary calcium excretion 1
• Do not restrict calcium intake excessively in primary hyperparathyroidism, as this paradoxically increases PTH 5
• Do not use calcimimetics in pseudohypoparathyroidism, as the problem is PTH resistance, not excess production 7