What are the diagnostic steps and treatment options for hyperparathyroidism?

Hyperparathyroidism Diagnosis and Treatment

The diagnosis of hyperparathyroidism requires measurement of serum calcium, phosphorus, and intact parathyroid hormone (iPTH), with iPTH being the most critical diagnostic test, followed by appropriate imaging for surgical planning if indicated. 1

Diagnostic Approach

Initial Laboratory Evaluation

• Essential tests:
  • Serum calcium (total and ionized)
  • Intact parathyroid hormone (iPTH)
  • Serum phosphorus
  • 25-OH vitamin D level
  • Renal function tests
  • Magnesium levels

Diagnostic Patterns by Type

Primary Hyperparathyroidism (PHPT)

• Elevated or high-normal serum calcium with elevated or inappropriately normal iPTH
• Low or low-normal serum phosphorus due to PTH's phosphaturic effect
• Must rule out vitamin D deficiency as a concomitant cause of secondary hyperparathyroidism

Secondary Hyperparathyroidism

• Normal or low serum calcium
• Elevated iPTH
• Common causes: chronic kidney disease, vitamin D deficiency, malabsorption

Tertiary Hyperparathyroidism

• Elevated serum calcium
• Elevated iPTH
• Typically occurs after long-standing secondary hyperparathyroidism (e.g., in advanced CKD)

Monitoring Recommendations

For CKD patients, calcium and phosphorus should be measured at the following intervals:

CKD Stage	Calcium & Phosphorus Monitoring
Stage 3	Every 6-12 months
Stage 4	Every 3-6 months
Stage 5	Every 1-3 months
Dialysis	Monthly

Treatment Options

Primary Hyperparathyroidism

Surgical Management

• Parathyroidectomy is the definitive treatment for primary hyperparathyroidism 1
• Indications for surgery:
  • Symptomatic hypercalcemia
  • Severe hypercalcemia
  • Osteoporosis
  • Age <50 years
  • Creatinine clearance <60 mL/min/1.73 m²
  • Nephrolithiasis or nephrocalcinosis

Surgical Approaches

• Bilateral neck exploration (BNE) - traditional approach
• Minimally invasive parathyroidectomy (MIP) - focused approach when localization studies identify a single adenoma
• Referral to a high-volume parathyroid surgeon is recommended for better outcomes

Medical Management (when surgery is contraindicated)

• Cinacalcet for patients unable to undergo surgery
  • Starting dose: 30 mg twice daily
  • Titrate every 2-4 weeks through sequential doses (30 mg twice daily → 60 mg twice daily → 90 mg twice daily → 90 mg 3-4 times daily) 2
  • Monitor serum calcium within 1 week after initiation or dose adjustment

Secondary Hyperparathyroidism in CKD

Medical Management

1. Dietary phosphorus restriction (800-1,000 mg/day)

2. Vitamin D therapy:

   • Correct vitamin D deficiency with nutritional supplements
   • For more advanced SHPT: Active vitamin D analogs (calcitriol)
     • Starting dose: 0.25-0.5 μg daily
     • Titrate based on serum calcium levels
     • May increase to 0.5-1.0 μg daily as needed 1

3. Calcimimetics (for dialysis patients):

   • Cinacalcet starting dose: 30 mg once daily
   • Titrate every 2-4 weeks through sequential doses (30,60,90,120,180 mg once daily)
   • Target iPTH levels: 150-300 pg/mL
   • Monitor serum calcium and phosphorus within 1 week and iPTH 1-4 weeks after initiation or dose adjustment 2

4. Treatment approach based on PTH levels:

   PTH Level	Treatment Approach
   Mildly elevated	Optimize calcium and vitamin D 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

Surgical Management

• Reserved for severe cases unresponsive to medical management
• Surgical options:
  • Subtotal parathyroidectomy (removal of 3.5 parathyroid glands)
  • Total parathyroidectomy with autotransplantation (tPTX+AT)
  • Total parathyroidectomy without autotransplantation (tPTX)
  • Total parathyroidectomy is associated with lower recurrence rates but higher risk of hypoparathyroidism 1

Monitoring and Follow-up

After Medical Treatment

• Serum calcium and phosphorus: Every 1-2 weeks during initial treatment, monthly for 3 months after stabilization, then every 3 months
• Target serum calcium: Low-normal range (8.5-9.0 mg/dL)
• Adjust calcitriol dose based on calcium levels (reduce by 50% if calcium exceeds 9.5 mg/dL)

After Surgical Treatment

• Close monitoring of calcium levels to detect hungry bone syndrome
• Aggressive calcium and vitamin D supplementation as needed
• Regular follow-up of calcium, phosphorus, and PTH levels

Common Pitfalls to Avoid

1. Ignoring vitamin D status - Vitamin D deficiency can cause secondary hyperparathyroidism and affect PTH levels
2. Biotin interference - Can result in falsely high or low PTH results depending on assay design
3. Overlooking familial hypocalciuric hypercalcemia - Check urinary calcium-to-creatinine clearance ratio (if <0.01, consider this diagnosis)
4. Relying solely on serum calcium - Ionized calcium may be more sensitive for diagnosis in some cases 3
5. Performing parathyroidectomy in patients with calciphylaxis without documented hyperparathyroidism

By following this diagnostic and treatment algorithm, clinicians can effectively manage patients with various forms of hyperparathyroidism, improving outcomes related to morbidity, mortality, and quality of life.