What labs are used to evaluate for hyperparathyroidism?

Laboratory Evaluation for Hyperparathyroidism

Measure serum calcium (corrected for albumin), intact parathyroid hormone (iPTH), and serum phosphate simultaneously to establish the diagnosis of hyperparathyroidism. 1, 2

Core Diagnostic Laboratory Tests

The essential laboratory panel includes:

• Serum calcium (total calcium corrected for albumin) is the primary screening test and should be measured simultaneously with PTH 1, 2
• Intact parathyroid hormone (iPTH) using immunoradiometric assay (IRMA) or immunochemiluminometric assay (ICMA) is required to distinguish primary from secondary hyperparathyroidism 3, 1
• Serum phosphate should be measured as hyperparathyroidism typically causes hypophosphatemia or low-normal levels 1, 2
• Serum creatinine and blood urea nitrogen to assess kidney function, as hypercalcemia can lead to kidney damage and chronic kidney disease causes secondary hyperparathyroidism 1, 2

Additional Essential Tests

• 25-hydroxyvitamin D levels must be measured to exclude vitamin D deficiency as a secondary cause of elevated PTH, as deficiency can complicate interpretation and coexist with hyperparathyroidism 1, 2
• 1,25-dihydroxyvitamin D should be measured in select cases to further evaluate vitamin D metabolism 1
• Serum albumin is necessary to correct total calcium values for accurate interpretation 2
• Alkaline phosphatase can provide additional information about bone turnover, though its predictive power in hyperparathyroidism is less established 3

Urine Studies

• 24-hour urine collection for calcium, creatinine, oxalate, uric acid, citrate, sodium, and potassium helps evaluate complications and metabolic abnormalities 2
• Random spot urine calcium/creatinine ratio should be evaluated to assess for hypercalciuria 1
• Urine calcium >400 mg/day on 24-hour collection identifies patients at increased risk for kidney stones and bone complications 2

Diagnostic Patterns

Primary Hyperparathyroidism

• Hypercalcemia or high-normal calcium with elevated or inappropriately normal PTH levels 2, 4
• Low or low-normal serum phosphate 2
• Note that 3% of patients with surgically proven primary hyperparathyroidism may have both calcium and PTH within reference ranges 5

Secondary Hyperparathyroidism

• Normal or low serum calcium with elevated PTH 2
• Commonly seen in chronic kidney disease or vitamin D deficiency 2
• For CKD patients with GFR <60 mL/min/1.73 m², measure calcium, phosphorus, and intact PTH with frequency based on CKD stage 3

Tertiary Hyperparathyroidism

• Hypercalcemia with elevated PTH, typically in end-stage renal disease 2

Monitoring Frequency

• Initial evaluation: Measure serum calcium and phosphorus at least every 2 weeks for 1 month when initiating or adjusting therapy 3
• Ongoing monitoring: After stabilization, measure monthly for 3 months, then every 3 months once target levels are achieved 3
• CKD patients: Frequency depends on CKD stage, with more frequent monitoring in advanced stages 3

Critical Technical Considerations

• Use assay-specific reference ranges for PTH, as different assay generations measure different PTH fragments and can significantly affect interpretation 1, 2
• Collect blood in EDTA tubes for PTH measurement, as PTH is most stable in EDTA plasma 2
• Use the same PTH assay for all measurements in the same patient to ensure adequate evaluation of trends 6
• Biotin supplements can interfere with some PTH assays, potentially causing falsely elevated or decreased results 1, 2

Important Caveats to Avoid Misdiagnosis

• Do not overlook vitamin D deficiency, which can suppress urine calcium excretion and mask hypercalciuria in primary hyperparathyroidism patients 2
• Consider race, age, and BMI when interpreting results, as PTH is higher in Black individuals, increases with age, and is higher in obese patients 1
• Measure ionized calcium in patients with osteoporosis and normal total calcium, as 95% of normocalcemic hyperparathyroidism cases show elevated ionized calcium 7
• Recognize normocalcemic hyperparathyroidism: 21% of primary hyperparathyroidism patients have calcium ≤10.5 mg/dL with PTH ≥65 pg/mL 5
• Exclude secondary causes before diagnosing normocalcemic primary hyperparathyroidism, including medications and medical conditions that stimulate PTH secretion 8

When to Consider Specialist Referral

• Referral to nephrologist and/or endocrinologist should be considered for persistent hypercalcemia, hypercalciuria, or nephrocalcinosis 1
• Patients with suspected multiple endocrine neoplasia syndromes require specialized evaluation 2