What is the treatment approach for hyperparathyroidism?

Treatment of Hyperparathyroidism

For primary hyperparathyroidism, parathyroidectomy is the definitive treatment and should be performed in symptomatic patients or those meeting specific surgical criteria, while asymptomatic patients may be observed with close monitoring. 1, 2

Primary Hyperparathyroidism (PHPT)

Surgical Management - The Definitive Treatment

Parathyroidectomy is indicated for:

• All symptomatic patients with bone pain, nephrolithiasis, neuromuscular symptoms, or neurocognitive disorders 1, 3
• Age younger than 50 years 4, 5
• Serum calcium >1 mg/dL above upper limit of normal 4, 5
• Creatinine clearance <60 mL/min per 1.73 m² 5
• Osteoporosis (T-score ≤-2.5 at any site) 4, 5
• Nephrolithiasis or nephrocalcinosis 4, 5
• Hypercalciuria (>400 mg per day) 6

Surgical Approach Selection

Minimally invasive parathyroidectomy (MIP) is preferred when:

• A single adenoma is confidently localized on preoperative imaging 1, 2
• Intraoperative PTH monitoring confirms removal of hyperfunctioning gland 7, 1
• Appropriate for approximately 80% of PHPT patients 1

Bilateral neck exploration (BNE) is required when:

• Preoperative imaging is discordant or nonlocalizing 1, 2
• Multigland disease is suspected (particularly when PTH ≤50 pg/mL, as 58.9% have multigland disease) 1

Medical Management for Non-Surgical Candidates

Cinacalcet (calcimimetic agent) is FDA-approved for:

• Patients with primary HPT for whom parathyroidectomy would be indicated based on serum calcium levels but who are unable to undergo surgery 8
• Starting dose: 30 mg twice daily, titrated every 2-4 weeks through sequential doses up to 90 mg 3-4 times daily 8
• Effectively lowers serum calcium and PTH levels 4

Conservative management for asymptomatic patients not meeting surgical criteria:

• Optimize calcium intake (age-appropriate dietary recommendations) 9, 4
• Ensure vitamin D sufficiency (25-OH vitamin D >20 ng/mL) 9, 4
• Antiresorptive therapy (bisphosphonates or denosumab) for skeletal protection in patients with increased fracture risk 4

Monitoring for Non-Surgical Patients

Surveillance protocol:

• Serum calcium: biannually 6
• Urinary calcium excretion: annually 6
• Bone mineral density: annually 6
• Serum creatinine: annually 10

Common pitfall: Most asymptomatic patients managed conservatively will not develop complications, but some progress over time without reliable predictors, necessitating strict adherence to monitoring protocols 6.

Secondary Hyperparathyroidism (SHPT)

Medical Management - First-Line Approach

Initial treatment strategy:

• Dietary phosphate restriction 2
• Phosphate binders to control hyperphosphatemia 7, 2
• Correction of hypocalcemia with calcium supplementation 7, 2
• Vitamin D sterols (calcitriol, paricalcitol, or doxercalciferol) with dosage adjusted to severity 2

Vitamin D sterol dosing for peritoneal dialysis patients:

• Calcitriol: 0.5-1.0 μg orally 2-3 times weekly 2
• Doxercalciferol: 2.5-5.0 μg orally 2-3 times weekly 2

Monitoring during vitamin D therapy:

• Serum calcium and phosphorus: every 2 weeks for 1 month after initiation or dose increase, then monthly 2
• PTH: monthly for at least 3 months, then every 3 months once target achieved 2

Calcimimetics for Persistent SHPT

Cinacalcet may be considered for:

• Persistent secondary hyperparathyroidism despite medical therapy 2
• Starting dose: 30 mg once daily for dialysis patients 8
• Titrate every 2-4 weeks through sequential doses (30,60,90,120,180 mg once daily) to target iPTH 150-300 pg/mL 8

Critical warning: Cinacalcet is NOT indicated for CKD patients not on dialysis due to increased risk of hypocalcemia 8.

Cautions with cinacalcet:

• Risk of hypocalcemia requiring frequent calcium monitoring 2, 9
• Potential QT interval prolongation 2
• Monitor serum calcium within 1 week after initiation or dose adjustment 8

Surgical Management for Refractory SHPT

Parathyroidectomy is indicated when:

• Persistent iPTH >800 pg/mL associated with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 2
• Intractable pruritus (often when PTH >500 pg/mL) 1
• Severe skeletal symptoms or pathological fractures 1
• Calcium-phosphate product >70 mg²/dL² with extraskeletal calcifications 1

Surgical options:

• Subtotal parathyroidectomy 7, 2
• Total parathyroidectomy with parathyroid tissue autotransplantation 7, 2
• Total parathyroidectomy 7, 2

Critical consideration: Total parathyroidectomy is not recommended for patients who may subsequently receive kidney transplant, as calcium control becomes problematic post-transplant 2.

Common pitfall: All three surgical approaches have comparable efficacy and recurrence rates, but the choice should account for transplant candidacy 7.

Postoperative Management

Immediate postoperative monitoring:

• Ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 2
• Initiate calcium gluconate infusion if hypocalcemia develops 2
• Adjust phosphate binders based on serum phosphorus levels 2

Reoperative Cases

Preoperative imaging is essential for reoperative parathyroid surgery due to:

• Lower cure rates than first-time surgery 7
• Higher complication rates 7
• Need to identify postoperative changes from previous explorations 7, 2

Imaging modalities for localization:

• 99Tc-Sestamibi scan 2
• Ultrasound 2
• 4D-CT (multiphase CT with contrast showing unique perfusion characteristics) 7, 2
• MRI 2