What are the diagnostic criteria for primary hyperparathyroidism?

Diagnostic Criteria for Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is diagnosed through biochemical testing, with the diagnostic criteria including elevated or inappropriately normal parathyroid hormone (PTH) levels in the setting of hypercalcemia and low or low-normal phosphorus levels. 1

Essential Diagnostic Tests

Core Laboratory Tests

• Serum calcium (total and/or ionized) - elevated
• Intact parathyroid hormone (iPTH) - elevated or inappropriately normal for the calcium level
• Serum phosphorus - typically low or low-normal
• 25-OH vitamin D level - to rule out vitamin D deficiency as a contributing factor
• Renal function tests - to assess kidney involvement
• 24-hour urinary calcium - to evaluate for hypercalciuria 1

Biochemical Patterns

1. Classic PHPT:

   • Elevated serum calcium
   • Elevated or inappropriately normal PTH
   • Low or low-normal phosphorus

2. Normocalcemic PHPT Variant:

   • Normal serum calcium levels
   • Persistently elevated PTH
   • No obvious cause for secondary hyperparathyroidism 2

Important Diagnostic Considerations

Differential Diagnosis

• Secondary hyperparathyroidism (SHPT): Increased PTH in response to hypocalcemia due to:

  • Chronic kidney disease
  • Vitamin D deficiency
  • Malabsorption syndromes 2

• Tertiary hyperparathyroidism (THPT): Lack of PTH suppression despite rising calcium levels, typically in patients with long-standing SHPT, often after kidney transplantation 2

Key Distinction

• PHPT is a biochemical diagnosis - imaging has no role in confirming or excluding the diagnosis 2, 1
• Imaging is only used for preoperative localization after biochemical confirmation 2

Clinical Presentations

Symptomatic Presentation

• Non-specific symptoms of hypercalcemia
• Skeletal fragility and osteoporosis
• Nephrolithiasis and nephrocalcinosis 3

Asymptomatic Presentation

• Most common presentation in countries with routine biochemical screening
• Detected incidentally during routine laboratory testing 3, 4

Special Populations

Pediatric Considerations

• PHPT is rare in children but typically presents with symptomatic hypercalcemia
• Solitary parathyroid adenoma is the most common cause
• May occasionally present asymptomatically 5

Common Pitfalls to Avoid

1. Relying on imaging for diagnosis

   • Imaging is only for preoperative localization, not diagnosis 2, 1

2. Misinterpreting normal PTH levels

   • Even a "normal" PTH level is inappropriate in the setting of hypercalcemia and should raise suspicion for PHPT 1

3. Overlooking vitamin D deficiency

   • Can mask hypercalcemia in PHPT and should be assessed 1

4. Failing to exclude familial forms

   • Consider genetic testing in selected patients, especially those with young age of onset, multiglandular disease, or family history 6

5. Missing normocalcemic variant

   • PHPT can present with normal calcium levels but elevated PTH in the absence of other causes 4

By following these diagnostic criteria and avoiding common pitfalls, clinicians can accurately diagnose primary hyperparathyroidism and proceed with appropriate management decisions.