What are the diagnostic tests for hyperparathyroidism?

Diagnosis of Hyperparathyroidism

Hyperparathyroidism is diagnosed by simultaneously measuring serum calcium (corrected for albumin) and intact parathyroid hormone (PTH), with the hallmark finding being elevated calcium alongside elevated or inappropriately normal PTH levels. 1

Core Diagnostic Laboratory Panel

The following tests must be obtained simultaneously to establish the diagnosis:

• Serum calcium (total calcium corrected for albumin) — This is the primary screening test, as hypercalcemia is the hallmark of primary hyperparathyroidism 1
• Intact parathyroid hormone (PTH) — Must be measured at the same time as calcium; elevated or inappropriately normal PTH in the setting of hypercalcemia confirms primary hyperparathyroidism 1, 2
• Serum phosphorus — Typically shows hypophosphatemia or low-normal levels in hyperparathyroidism 1, 3, 2
• Serum creatinine and blood urea nitrogen — Essential to assess kidney function, as hypercalcemia can cause kidney damage and chronic kidney disease alters PTH interpretation 1, 3

Diagnostic Algorithm Based on Laboratory Results

Primary Hyperparathyroidism

• Elevated serum calcium + elevated or inappropriately normal PTH + low/low-normal phosphorus = Primary hyperparathyroidism 1
• Serum chloride may be elevated, which supports the diagnosis 1

Secondary Hyperparathyroidism

• Normal or low serum calcium + elevated PTH = Secondary hyperparathyroidism, commonly from chronic kidney disease or vitamin D deficiency 1, 2

Tertiary Hyperparathyroidism

• Hypercalcemia + elevated PTH in end-stage renal disease = Tertiary hyperparathyroidism 2

Additional Confirmatory Tests

After establishing the biochemical diagnosis, obtain:

• 25-hydroxyvitamin D levels — Crucial because vitamin D deficiency can complicate PTH interpretation and coexist with hyperparathyroidism 3, 2
• 24-hour urine collection for calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine to evaluate complications and metabolic abnormalities 1, 2
• Alkaline phosphatase — Can serve as a marker of severity of hyperparathyroid bone disease 1

Critical Technical Considerations to Avoid Misdiagnosis

PTH Assay Interpretation

• Use assay-specific reference ranges — Different PTH assay generations measure different PTH fragments and can yield significantly different results between laboratories 1, 3, 2
• Collect blood in EDTA tubes for PTH measurement, as PTH is most stable in EDTA plasma 1, 2

Patient-Specific Factors Affecting PTH Levels

• Race — PTH is higher in Black individuals 1, 3
• Age — PTH increases with age 1, 3
• BMI — PTH is elevated in obese patients 1, 3

Common Pitfalls

• Biotin supplements (vitamin B7/B8) can interfere with PTH assays, causing falsely elevated or decreased results depending on assay design 1, 3, 2
• Not assessing vitamin D status when interpreting PTH levels can lead to misdiagnosis, as vitamin D deficiency can cause secondary elevation of PTH and suppress urine calcium excretion 3, 2
• Vitamin D deficiency can mask hypercalciuria in primary hyperparathyroidism patients 2

Monitoring Frequency

For Chronic Kidney Disease Patients

• CKD Stage 3-5: Measure calcium, phosphorus, and PTH based on CKD stage—more frequently if receiving treatment for abnormalities 1, 3

For Patients on Treatment

• Monitor serum calcium and phosphorus at least monthly for the first 3 months, then every 3 months thereafter 1, 3

Clinical Context for Testing

Consider hyperparathyroidism in patients presenting with:

• Nephrolithiasis or nephrocalcinosis 4, 5
• Osteoporosis or pathologic fractures 4, 5
• Diffuse bone pain 6
• Cognitive or psychiatric disorders 6
• Asymptomatic hypercalcemia discovered incidentally 4, 7