What are the treatment options for hyperparathyroidism?

Treatment of Hyperparathyroidism

Surgery is the only curative treatment for primary hyperparathyroidism, while secondary hyperparathyroidism requires a stepwise medical approach starting with phosphate control and vitamin D repletion, reserving surgery only for severe refractory cases. 1

Primary Hyperparathyroidism

Surgical Management

Parathyroidectomy is the definitive treatment and should be performed in patients with symptomatic disease (kidney stones, bone pain, fractures, neuromuscular symptoms), osteoporosis on DEXA, hypercalciuria, impaired kidney function (GFR <60 mL/min/1.73 m²), age ≤50 years, or serum calcium >1 mg/dL above upper limit of normal. 2, 3

Two surgical approaches are equally effective:

• Minimally invasive parathyroidectomy (MIP) offers shorter operating times, faster recovery, and decreased perioperative costs compared to bilateral neck exploration 1
• MIP requires confident preoperative localization of a single parathyroid adenoma using 99Tc-Sestamibi scan (highest sensitivity) and intraoperative PTH monitoring 1, 2
• Bilateral neck exploration (BNE) remains necessary for discordant/nonlocalizing imaging or suspected multigland disease 1

Critical point: Negative imaging is not a contraindication for surgery and does not determine surgical indication 4

Medical Management (Non-Surgical Candidates Only)

For patients unable to undergo parathyroidectomy, cinacalcet is FDA-approved for treatment of hypercalcemia in primary hyperparathyroidism when surgery would be indicated based on calcium levels but cannot be performed 5

Secondary Hyperparathyroidism

Stepwise Medical Algorithm

Step 1: Control Hyperphosphatemia (FIRST PRIORITY)

• Target serum phosphorus 3.5-5.5 mg/dL for stage 5 CKD 6
• Initiate dietary phosphorus restriction to 800-1,000 mg/day 6
• Add phosphate binders (calcium-based or non-calcium based) 1, 6
• Monitor serum phosphorus monthly after initiating therapy 6

Step 2: Correct Hypocalcemia

• Provide supplemental calcium carbonate 1-2 g three times daily with meals (serves dual purpose as phosphate binder and calcium supplement) 6
• Monitor calcium levels within 1 week of initiating therapy 6

Step 3: Vitamin D Therapy

• Do NOT initiate active vitamin D therapy until serum phosphorus falls below 4.6 mg/dL (critical to avoid vascular calcification) 6
• Replete 25(OH)D with ergocalciferol 50,000 IU monthly if <30 ng/mL 6
• For hemodialysis patients: intermittent intravenous calcitriol or paricalcitol is more effective than oral administration 6
• For peritoneal dialysis patients: oral calcitriol 0.5-1.0 μg or doxercalciferol 2.5-5.0 μg given 2-3 times weekly 1
• Target PTH 150-300 pg/mL for dialysis patients, NOT normal range (targeting normal PTH causes adynamic bone disease with increased fracture risk) 6

Monitoring during vitamin D therapy:

• Serum calcium and phosphorus every 2 weeks for 1 month, then monthly 1, 6
• PTH monthly for at least 3 months, then every 3 months once target achieved 1, 6
• Reduce or discontinue vitamin D if calcium rises above 10.2 mg/dL 6

Step 4: Add Calcimimetics for Persistent Elevation

• Consider cinacalcet (FDA-approved for secondary hyperparathyroidism in CKD patients on dialysis), etelcalcetide, evocalcet, or upacicalcet if PTH remains elevated despite optimized vitamin D therapy 6, 5
• Start cinacalcet at 30 mg once daily, titrate no more frequently than every 2-4 weeks to target iPTH 150-300 pg/mL 2
• Caution: Risk of hypocalcemia and increased QT interval 1, 2

Limitations: Cinacalcet is NOT indicated for CKD patients not on dialysis due to increased risk of hypocalcemia 5

Surgical Management of Secondary Hyperparathyroidism

Indications for parathyroidectomy:

• Persistent PTH >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 1, 6
• Reassess after 3-6 months of optimized medical therapy 6
• Severe hyperparathyroidism with hypercalcemia that precludes medical therapy 6

Surgical options:

• Total parathyroidectomy (TPTX) may be superior to total parathyroidectomy with autotransplantation (TPTX+AT) with lower recurrence rates (OR 0.17,95% CI 0.06-0.54) and shorter operative time 6
• TPTX has higher risk of hypoparathyroidism (OR 2.97,95% CI 1.09-8.08) but studies show no permanent hypocalcemia or adynamic bone disease 6
• Alternative options: subtotal parathyroidectomy or TPTX+AT 1, 6
• Do NOT perform total parathyroidectomy in patients who may subsequently receive kidney transplant (problematic calcium control) 1
• Observational data shows parathyroidectomy associated with lower mortality than calcimimetics and more substantial increase in bone mineral density 6

Postoperative management:

• Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 1, 6
• Initiate calcium gluconate infusion as needed 1
• Adjust phosphate binders based on serum phosphorus levels 1
• Hypocalcemia is common and managed with calcium and vitamin D supplementation 6

Critical Pitfalls to Avoid

• Never start vitamin D therapy with uncontrolled hyperphosphatemia - this worsens vascular calcification and increases calcium-phosphate product 6
• Never target normal PTH levels (<65 pg/mL) in dialysis patients - causes adynamic bone disease with increased fracture risk 6
• Always confirm diagnosis biochemically before treatment - measure serum calcium (corrected for albumin) and intact PTH simultaneously, assess vitamin D status 2
• PTH assays vary significantly between laboratories - use assay-specific reference values 2
• For reoperative parathyroid surgery, perform preoperative imaging (99Tc-Sestamibi, ultrasound, CT, or MRI) to localize target lesions 1