What blood tests are needed for a suspected parathyroid tumor?

Blood Tests for Suspected Parathyroid Tumor

For a suspected parathyroid tumor, measure serum calcium and parathyroid hormone (PTH) levels as the essential initial blood tests, with additional testing for phosphate, vitamin D, and creatinine to complete the diagnostic evaluation. 1, 2

Essential Initial Blood Tests

Primary Diagnostic Tests

• Serum calcium is the cornerstone test, as hypercalcemia combined with elevated or inappropriately normal PTH defines primary hyperparathyroidism (PHPT), the most common presentation of parathyroid tumors 1
• Intact parathyroid hormone (PTH) distinguishes PHPT from other causes of hypercalcemia such as malignancy or sarcoidosis 1
• Serum phosphate should be measured, as hypophosphatemia is characteristic of hyperparathyroidism 2

Supporting Laboratory Tests

• Serum creatinine to assess kidney function (GFR), as this affects PTH interpretation and surgical candidacy 1, 2
• Vitamin D (25-hydroxyvitamin D) levels, since vitamin D deficiency can elevate PTH and must be corrected before interpreting results 1, 2
• Albumin or ionized calcium if total calcium is borderline, to correct for protein binding 2

Additional Tests for Specific Clinical Scenarios

When Malignancy is Suspected

• Parathyroid hormone-related protein (PTHrP) should be measured if PTH is low or suppressed in the setting of hypercalcemia, as this suggests humoral hypercalcemia of malignancy rather than a parathyroid tumor 1, 3
• PTHrP has 81% sensitivity for identifying hypercalcemia from solid tumors and effectively distinguishes malignancy-associated hypercalcemia from PHPT 3

For Parathyroid Carcinoma Evaluation

• Markedly elevated calcium (often >14 mg/dL) and very high PTH levels (often >5 times upper limit of normal) suggest possible parathyroid carcinoma rather than adenoma 4
• Consider alkaline phosphatase as a marker of bone turnover in severe cases 4

To Exclude Familial Hypocalciuric Hypercalcemia (FHH)

• 24-hour urine calcium or preferably calcium-to-creatinine clearance ratio (CCCR) should be measured to exclude FHH before considering surgery 5
• A CCCR below 0.020 should raise suspicion for FHH and prompt genetic testing; a ratio below 0.015 has higher positive predictive value for FHH 5
• This distinction is critical because FHH does not require surgery, while PHPT does 5

Important Testing Considerations

Sample Handling and Timing

• EDTA plasma is preferred over serum for PTH measurement due to better stability 1, 2
• PTH has a circadian rhythm, though optimal sampling time remains undefined 1, 2
• Store samples at 4°C rather than room temperature for optimal PTH stability 2

Assay-Related Factors

• Different PTH assay generations (second vs. third generation) can yield varying results, but both have similar diagnostic sensitivity for PHPT 1
• Biotin supplements can interfere with PTH assays, causing falsely high or low results depending on the assay design 1, 2
• Patient factors affecting PTH include race, age, BMI, and vitamin D status 1, 2

Common Pitfalls to Avoid

Low-Normal PTH in PHPT

• A low-normal PTH does not exclude PHPT if calcium is elevated 6
• Atypical PTH molecules or post-translational modifications can cause falsely low PTH readings in some parathyroid adenomas 6
• Consider repeat PTH measurement with serial dilutions if PHPT is strongly suspected despite low-normal PTH 6

Renal Function Impact

• PTH elevates with declining kidney function; interpret elevated PTH cautiously in patients with GFR <45 mL/min/1.73 m² 2
• Secondary hyperparathyroidism from chronic kidney disease can mimic PHPT biochemically but requires different management 2, 7

Vitamin D Deficiency

• Correct vitamin D deficiency first before interpreting PTH elevation, as secondary hyperparathyroidism from vitamin D deficiency can confound diagnosis 1, 2
• Reference ranges for PTH are 20% lower in vitamin D-replete individuals 1