What labs are used to diagnose hyperparathyroidism?

Laboratory Tests for Diagnosing Hyperparathyroidism

The diagnosis of hyperparathyroidism requires simultaneous measurement of serum calcium and intact parathyroid hormone (iPTH) as the essential laboratory tests. 1

Core Diagnostic Tests

• Serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH) should be measured simultaneously to establish the diagnosis 1, 2
• Serum phosphate levels should be measured as hyperparathyroidism typically causes hypophosphatemia 2
• 25-hydroxyvitamin D levels must be assessed to exclude vitamin D deficiency as a secondary cause of elevated PTH 3, 2
• Serum creatinine and blood urea nitrogen (BUN) to evaluate kidney function, as hypercalcemia can affect renal function 3
• Urine calcium/creatinine ratio in a random spot urine to assess for hypercalciuria 3

Diagnostic Algorithm

1. Initial screening: Measure serum calcium (corrected for albumin) and iPTH simultaneously 1

   • Primary hyperparathyroidism: Elevated or high-normal calcium with inappropriately normal or elevated PTH 2, 4
   • Secondary hyperparathyroidism: Normal or low calcium with elevated PTH 1
   • Tertiary hyperparathyroidism: Hypercalcemia with elevated PTH (often in end-stage renal disease) 1

2. Additional tests to confirm diagnosis:

   • Serum phosphate (typically low in primary hyperparathyroidism) 2
   • Calcium-to-creatinine clearance ratio (to rule out familial hypocalciuric hypercalcemia if ratio <0.01) 5
   • 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels 3, 5
   • Serum chloride (chloride/phosphate ratio >33 suggests primary hyperparathyroidism) 5

Special Considerations

• Use assay-specific reference ranges for PTH, as different assay generations measure different PTH fragments 2, 3
• Be aware that vitamin D deficiency can coexist with and complicate the diagnosis of hyperparathyroidism 3
• Consider factors that can affect calcium and PTH levels:
  • Race (PTH is higher in Black individuals compared to White individuals) 2
  • Age (PTH increases with age) 2
  • BMI (PTH is higher in obese patients) 2
  • Biotin supplements can interfere with some PTH assays 2, 3

Atypical Presentations

• Normocalcemic hyperparathyroidism: Normal calcium with elevated PTH (after excluding secondary causes) 6, 7
• Normohormonal hyperparathyroidism: Elevated calcium with PTH in the normal range 6
• In cases where both calcium and PTH are within reference ranges but hyperparathyroidism is suspected, a calcium-PTH nomogram may help distinguish between normal patients and those with atypical primary hyperparathyroidism 6

Monitoring Parameters

• For patients on treatment for secondary hyperparathyroidism, monitor serum calcium and phosphorus monthly for the first 3 months, then every 3 months thereafter 3
• Serial assessments of phosphate, calcium, and PTH levels should be considered together for ongoing management 3

Common Pitfalls to Avoid

• Not assessing vitamin D status when interpreting PTH levels 3
• Using different PTH assay generations without considering their varying sensitivity to PTH fragments 2, 3
• Failing to correct calcium for albumin levels 1
• Not considering familial hypocalciuric hypercalcemia in patients with hypercalcemia, normal/elevated PTH, and low urinary calcium excretion 5