Is ordering blood work for parathyroid hormone (PTH) sufficient to check for abnormal parathyroid function?

Checking for Abnormal Parathyroid Function

No, ordering PTH alone is insufficient—you must simultaneously measure serum calcium (corrected for albumin) along with PTH to properly assess parathyroid function. 1

Essential Initial Laboratory Panel

The diagnosis of parathyroid disorders fundamentally depends on the relationship between calcium and PTH, not PTH in isolation:

• Measure serum calcium (total calcium corrected for albumin) and intact PTH simultaneously as the cornerstone of parathyroid assessment 1
• Add serum phosphate to the initial panel, as it is typically low or low-normal in primary hyperparathyroidism 1
• Measure serum creatinine to evaluate kidney function, which is essential for proper interpretation 1
• Check 25-hydroxyvitamin D status, as vitamin D deficiency profoundly complicates PTH interpretation and can mask or mimic parathyroid disease 1, 2

Why PTH Alone Fails Diagnostically

The clinical interpretation of PTH is entirely context-dependent on the calcium level:

• Primary hyperparathyroidism: Hypercalcemia with elevated OR inappropriately normal PTH 1
• Secondary hyperparathyroidism: Normal or low calcium with elevated PTH (seen in chronic kidney disease or vitamin D deficiency) 1
• Tertiary hyperparathyroidism: Hypercalcemia with elevated PTH in end-stage renal disease 1
• An elevated PTH with low calcium indicates appropriate parathyroid response, not parathyroid disease 3

Critical Technical Considerations

PTH measurement has significant analytical challenges that affect interpretation:

• Use assay-specific reference ranges—different PTH assay generations measure different PTH fragments and can vary by up to 47% 3, 4
• Second-generation assays measure C-terminal fragments with longer half-lives and may overestimate functional parathyroid tissue 3
• Third-generation assays measure only full-length PTH and show more rapid decline after parathyroid removal 3
• All serial measurements must use the same assay in the same laboratory to ensure accurate trend evaluation 3, 4

Frequency of Monitoring (For Chronic Kidney Disease)

For patients with CKD and GFR <60 mL/min/1.73 m², measure calcium, phosphorus, and intact PTH at intervals based on CKD stage 5:

• More frequent monitoring is required if the patient receives treatment for abnormalities in calcium, phosphorus, or PTH 5
• Measurements may be done less frequently for those with PTH levels at the low end of target ranges 5

Common Pitfalls to Avoid

• Not assessing vitamin D status when interpreting PTH levels leads to misdiagnosis—vitamin D deficiency causes secondary hyperparathyroidism that mimics primary disease 1, 2
• Ordering PTH without calcium prevents distinguishing primary hyperparathyroidism from appropriate parathyroid responses 1
• Using different PTH assay generations without considering their varying sensitivity results in inaccurate diagnoses 5, 1
• Biotin supplements can interfere with PTH assays, causing under- or overestimation depending on assay design 5
• Blood samples should ideally be collected in EDTA tubes for PTH measurement, as PTH is most stable in EDTA plasma 5, 2

Additional Testing for Specific Scenarios

If hypercalcemia is confirmed with inappropriately normal or elevated PTH:

• 24-hour urine collection for calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine helps evaluate complications 1
• Serum chloride and uric acid may suggest underlying conditions associated with stone disease 1
• If PTH is low or low-normal in the setting of hypercalcemia, consider PTH-related peptide (PTHrP) testing for malignancy-associated hypercalcemia—but only after confirming PTH is suppressed 6