What are the treatment options for primary, secondary, and tertiary hyperparathyroidism?

Treatment Options for Primary, Secondary, and Tertiary Hyperparathyroidism

Surgical intervention is the definitive treatment for primary hyperparathyroidism, while secondary hyperparathyroidism requires medical management targeting the underlying cause, and tertiary hyperparathyroidism typically necessitates parathyroidectomy when medical therapy fails. 1, 2

Primary Hyperparathyroidism (PHPT)

Surgical Management

• Parathyroidectomy is the treatment of choice for symptomatic patients with PHPT 1, 3

• Two main surgical approaches:

  1. Bilateral Neck Exploration (BNE): Traditional approach where all parathyroid glands are identified and examined
  2. Minimally Invasive Parathyroidectomy (MIP): Targeted removal of affected gland(s) with limited dissection 1

• MIP offers advantages including:

  • Shorter operating times
  • Faster recovery
  • Decreased perioperative costs 1
  • Requires precise preoperative localization of adenoma(s) 4

• Indications for surgery (per NIH Consensus):

  • All symptomatic patients
  • Asymptomatic patients who are:
    • Younger than 50 years
    • Have severe hypercalcemia
    • Markedly reduced creatinine clearance
    • Profound osteopenia 4

Medical Management

• Reserved for patients unable to undergo parathyroidectomy 5
• Options include:
  • Cinacalcet: FDA-approved for hypercalcemia in PHPT patients who cannot undergo surgery 5
  • Vitamin D supplementation if deficient
  • Calcium supplementation as needed 2

Secondary Hyperparathyroidism (SHPT)

Medical Management

• Treatment depends on underlying cause (most commonly CKD) 1, 2

• For CKD-related SHPT:

  1. Phosphate control:

     • Dietary phosphorus restriction (800-1000 mg/day) 2
     • Phosphate binders 2

  2. Vitamin D therapy:

     • Active vitamin D analogs (calcitriol) 2

  3. Calcimimetics:

     • Cinacalcet: Indicated for SHPT in adult patients with CKD on dialysis 5
     • Dosing starts at 30 mg once daily with food
     • Titrate every 2-4 weeks to target iPTH 150-300 pg/mL 5
     • Monitor serum calcium frequently during titration 5
     • Important: Not indicated for CKD patients not on dialysis due to increased hypocalcemia risk 5

• Treatment approach based on PTH levels:

  • 150-300 pg/mL: Maintain current therapy
  • 300-500 pg/mL: Increase vitamin D sterols, adjust phosphate binders
  • 500-800 pg/mL: Higher doses of vitamin D sterols, consider adding cinacalcet

  • 800 pg/mL: Consider parathyroidectomy if medical therapy fails 2

Surgical Management

• Indicated for medically refractory SHPT 1

• Surgical options:

  1. Subtotal Parathyroidectomy (SPTX): Removal of three and a half glands
  2. Total Parathyroidectomy (TPTX): Removal of all parathyroid tissue
  3. Total Parathyroidectomy with Autotransplantation (TPTX+AT): All glands removed with reimplantation of tissue fragments 1

• Controversy exists regarding optimal surgical approach:

  • SPTX has higher recurrence rates due to hyperplasia of residual tissue 1
  • TPTX may cause persistent hypocalcemia but has lower recurrence rates 1
  • TPTX+AT reduces risk of permanent hypoparathyroidism but has higher recurrence rates than TPTX 1

Tertiary Hyperparathyroidism (THPT)

• Occurs when parathyroid glands become autonomous after long-standing SHPT, often following kidney transplantation 1, 6

Medical Management

• May become resistant to calcimimetic treatment 6
• Trial of medical therapy similar to SHPT may be attempted initially

Surgical Management

• Primary treatment is surgery for persistent hypercalcemia and/or elevated PTH 6

• Surgical options:

  1. Total parathyroidectomy with or without autotransplantation
  2. Subtotal parathyroidectomy
  3. Limited parathyroidectomy 6
  • Important to remove superior parts of thymus as well 6

• Percutaneous ethanol injection has been used but has poor long-term results compared to surgery 7

Monitoring and Follow-up

• Regular monitoring of calcium, phosphorus, and PTH levels:

  • Every 3-6 months initially
  • Every 6-12 months once stable 2

• Target PTH levels by CKD stage:

  • CKD G3: <70 pg/mL
  • CKD G4: <110 pg/mL
  • CKD G5: <300 pg/mL
  • CKD G5D: 150-600 pg/mL 2

• Monitor for complications:

  • Bone disease
  • Kidney stones
  • Cardiovascular calcifications 2

Common Pitfalls and Caveats

1. Delayed diagnosis: Asymptomatic PHPT may be missed without routine calcium screening
2. Inadequate preoperative localization: Critical for successful MIP in PHPT
3. Overlooking vitamin D deficiency: Can exacerbate SHPT and should be corrected
4. Cinacalcet use in non-dialysis CKD patients: Contraindicated due to hypocalcemia risk 5
5. Persistent or recurrent disease: May occur after subtotal parathyroidectomy or TPTX+AT 1
6. Failure to remove all hyperfunctioning tissue: Can lead to persistent hyperparathyroidism