What are the diagnostic tests for secondary hyperparathyroidism?

Diagnostic Tests for Secondary Hyperparathyroidism

The primary diagnostic tests for secondary hyperparathyroidism include serum parathyroid hormone (PTH), calcium, phosphorus, vitamin D levels, and renal function tests. These tests should be performed when GFR falls below 60 mL/min/1.73 m² and monitored regularly thereafter 1.

Essential Laboratory Tests

First-line Tests

• Parathyroid hormone (PTH):

  • Elevated levels are the hallmark of secondary hyperparathyroidism
  • Intact PTH (iPTH) is the preferred measurement
  • Target ranges vary by CKD stage 2:
    • CKD G3: <70 pg/mL
    • CKD G4: <110 pg/mL
    • CKD G5: <300 pg/mL
    • CKD G5D: 150-600 pg/mL

• Serum calcium: Usually normal or low in secondary hyperparathyroidism

• Serum phosphorus: Often elevated, especially in CKD-related secondary hyperparathyroidism

• 25-hydroxyvitamin D: To assess vitamin D status (deficiency is a common cause)

• 1,25-dihydroxyvitamin D: Often low in secondary hyperparathyroidism

• Renal function tests: Creatinine and estimated GFR to assess kidney function

Additional Tests

• Alkaline phosphatase (ALP): A reliable biomarker of bone turnover and osteomalacia 1

  • In children: Total ALP (as bone-specific ALP represents 80-90% of total)
  • In adults: Bone-specific ALP preferred (as only ~50% of circulating ALP originates from bone)

• Tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR): Helps assess renal phosphate handling 1

Timing and Monitoring

• Serum calcium and phosphorus should be measured within 1 week of treatment initiation or dose adjustment 2, 3
• PTH should be measured 1-4 weeks after treatment initiation or dose adjustment 3
• Regular monitoring should continue every 3-6 months initially, then every 6-12 months once stable 2

Important Considerations for PTH Measurement

• Different PTH assays (generations) can yield different results due to detection of various PTH fragments 1
• Second-generation (intact PTH) assays may overestimate biologically active PTH by detecting C-terminal fragments 1
• Third-generation assays have been developed to overcome this problem but are not yet standard clinical tools 1
• Use assay-specific reference ranges when interpreting results 1
• Treatment decisions should be based on trends rather than single measurements 2

Diagnostic Algorithm

1. Initial screening: Measure serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and renal function
2. Confirm diagnosis: Elevated PTH with normal/low calcium suggests secondary hyperparathyroidism
3. Determine etiology:
   • If eGFR <60 mL/min/1.73 m²: Consider CKD-related secondary hyperparathyroidism
   • If vitamin D <30 ng/mL: Consider vitamin D deficiency
   • If calcium is low with normal renal function: Consider inadequate calcium intake 4
4. Calcium challenge test: For suspected calcium deficiency, a trial of calcium supplementation (600 mg twice daily) with PTH retesting after 2-3 weeks can confirm this etiology 4

Pitfalls and Caveats

• PTH has significant biological variation (20% in healthy individuals, up to 30% in hemodialysis patients) 1
• Preanalytical conditions affect PTH measurement; EDTA plasma is preferred over serum 1
• Biotin supplements can interfere with PTH assays, causing under or overestimation 1
• PTH levels are race-dependent (higher in Black compared to white individuals) and correlate with BMI 1
• PTH increases with age, possibly due to declining GFR 1

By systematically evaluating these parameters, clinicians can accurately diagnose secondary hyperparathyroidism and determine its underlying cause, which is essential for appropriate management and prevention of complications such as metabolic bone disease, cardiovascular calcifications, and immune dysfunction 5.