What are the types and treatments for hyperparathyroidism?

Types and Treatments for Hyperparathyroidism

Hyperparathyroidism is classified into three main types: primary, secondary, and tertiary, with surgical intervention being the definitive treatment for primary and tertiary hyperparathyroidism, while secondary hyperparathyroidism is initially managed medically with calcium, vitamin D, and phosphate control. 1, 2

Types of Hyperparathyroidism

1. Primary Hyperparathyroidism (PHPT)

• Most common cause of hypercalcemia 2
• Characterized by autonomous overproduction of parathyroid hormone (PTH)
• Often caused by a single parathyroid adenoma
• Presents with elevated calcium levels without appropriate suppression of PTH 2

2. Secondary Hyperparathyroidism (SHPT)

• Results from compensatory increase in PTH due to chronic hypocalcemia
• Most commonly associated with:
  • Chronic kidney disease (CKD)
  • Vitamin D deficiency
  • Gastrointestinal disorders affecting calcium absorption 2
• Characterized by normal or low calcium with elevated PTH levels

3. Tertiary Hyperparathyroidism (THPT)

• Occurs when longstanding secondary hyperparathyroidism leads to autonomous parathyroid function
• Often seen after kidney transplantation in patients with previous CKD
• Results in hypercalcemia with elevated PTH levels 3, 4
• Characterized by parathyroid glands that continue to oversecrete PTH despite normal or elevated calcium levels 3

Treatment Approaches

1. Primary Hyperparathyroidism Treatment

Surgical Management

• Parathyroidectomy is indicated when any of the following are present: 2
  • Symptomatic disease
  • Age ≤50 years
  • Serum calcium >1 mg/dL above upper limit of normal
  • Osteoporosis
  • Creatinine clearance <60 mL/min/1.73m²
  • Nephrolithiasis or nephrocalcinosis
  • Hypercalciuria

Surgical Approaches

• Minimally Invasive Parathyroidectomy (MIP):

  • Shorter operating times
  • Faster recovery
  • Decreased perioperative costs 1

• Bilateral Neck Exploration (BNE):

  • Traditional approach
  • May be necessary for multiple gland disease 1

Medical Management

• For patients unable to undergo surgery:
  • Cinacalcet starting at 30 mg twice daily, titrated every 2-4 weeks as needed 5
  • Monitor serum calcium every 2 months 5

2. Secondary Hyperparathyroidism Treatment

Medical Management

• For CKD patients on dialysis:

  • Optimize calcium and vitamin D levels
  • Control phosphate levels (dietary restriction to 800-1000 mg/day) 1
  • Cinacalcet starting at 30 mg once daily, titrated every 2-4 weeks 5
  • Target iPTH levels of 150-300 pg/mL 5

• Treatment based on PTH levels: 1

  • 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

• Important caveat: Cinacalcet is not indicated for CKD patients who are not on dialysis due to increased risk of hypocalcemia 5

3. Tertiary Hyperparathyroidism Treatment

Surgical Management

• Surgery is the primary treatment for persistent hypercalcemia and/or elevated PTH 3
• Three main surgical approaches:
  • Total Parathyroidectomy (TPTX): Lower recurrence rates but risk of permanent hypocalcemia 1, 3
  • Total Parathyroidectomy with Autotransplantation (TPTX+AT): Reduces risk of permanent hypoparathyroidism but higher recurrence rates 1, 3
  • Subtotal Parathyroidectomy (SPTX): Higher recurrence rates due to hyperplasia of residual tissue 1, 3
• Transcervical thymectomy should be performed with all procedures 6

Monitoring and Follow-up

For Secondary Hyperparathyroidism

• Monitor serum calcium and phosphorus within 1 week of treatment initiation or dose adjustment 5
• Check iPTH 1-4 weeks after treatment changes 5
• Target PTH levels vary by CKD stage: 1
  • CKD G3: <70 pg/mL
  • CKD G4: <110 pg/mL
  • CKD G5: <300 pg/mL
  • CKD G5D (dialysis): 150-600 pg/mL

For Primary and Tertiary Hyperparathyroidism

• Monitor serum calcium approximately every 2 months 5
• If serum calcium falls below 7.5 mg/dL or symptoms of hypocalcemia persist, withhold cinacalcet until calcium reaches 8 mg/dL 5

Special Considerations

Multiple Endocrine Neoplasia (MEN)

• Primary hyperparathyroidism is often the first and most common endocrinopathy in MEN type 1 6
• Genetic testing of family members is warranted 2
• Higher recurrence rates after surgery compared to sporadic hyperparathyroidism 6

Parathyroid Carcinoma

• Rare cause of hyperparathyroidism 2
• Treatment with cinacalcet starting at 30 mg twice daily, titrated every 2-4 weeks 5

Pitfalls and Caveats

• Unsuccessful surgical treatment is more common in MEN-associated hyperparathyroidism than in sporadic cases 6
• Factors affecting surgical success include:
  • Pre-operative diagnosis
  • Surgeon's experience
  • Timing of surgery
  • Intraoperative confirmation (histologic examination, rapid PTH assay) 6
• Patients should be referred to surgeons experienced in parathyroid surgery to minimize complications 1
• When switching from etelcalcetide to cinacalcet, discontinue etelcalcetide for at least 4 weeks and ensure corrected serum calcium is at or above the lower limit of normal 5