Laboratory Assessment for Parathyroid Conditions
When evaluating parathyroid conditions, serum levels of calcium, phosphorus, intact parathyroid hormone (PTH), and alkaline phosphatase activity should be measured as the core laboratory panel. 1
Core Laboratory Panel
Primary Tests
- Intact Parathyroid Hormone (PTH) - The central hormone in calcium homeostasis
- Serum Calcium - Total serum calcium
- Ionized Calcium - More sensitive than total calcium for detecting calcium abnormalities
- Phosphorus - Inversely related to PTH levels
- Alkaline Phosphatase - Marker of bone turnover
Secondary Tests
- 25-hydroxyvitamin D - To assess vitamin D status which affects PTH secretion
- Albumin - For correct interpretation of total calcium levels
- Creatinine/eGFR - To assess kidney function which affects PTH metabolism
Interpretation Considerations
PTH Measurement
PTH is measured using different generations of immunoassays:
- Second-generation assays (intact PTH assays) - Detect both full-length PTH and some fragments
- Third-generation assays - More specific for biologically active PTH 1
Important considerations:
- PTH assays vary significantly between laboratories (up to 5-fold differences) 2
- Results should be interpreted in relation to the specific assay used
- Sequential measurements should use the same assay for proper trend analysis
Calcium Assessment
- Ionized calcium >6.0 mg/dL has 91.3% association with positive parathyroid imaging 3
- Normal calcium with elevated PTH may indicate early primary hyperparathyroidism or secondary hyperparathyroidism
Phosphate Levels
- Phosphate <3.0 mg/dL has 70.7% association with positive parathyroid imaging 3
- Inverse relationship with PTH levels is diagnostically important
Testing Algorithm Based on Suspected Condition
For Primary Hyperparathyroidism
- Measure serum calcium, ionized calcium, PTH, phosphate
- If calcium is elevated with inappropriately normal or high PTH → diagnostic of primary hyperparathyroidism
- If calcium is normal but PTH is elevated → consider oral calcium loading test to confirm diagnosis 4
For Secondary Hyperparathyroidism
- Measure serum calcium, phosphate, PTH, alkaline phosphatase, 25-hydroxyvitamin D, and creatinine
- In CKD patients, frequency of testing should follow this schedule 1:
- GFR 30-59 ml/min/1.73m² (CKD Stage 3): At least annually
- GFR <30 ml/min/1.73m² (CKD Stages 4-5): At least twice yearly
- More frequent monitoring if receiving treatment for abnormalities
Common Pitfalls to Avoid
Relying on absolute PTH cutoff values - Guidelines should avoid absolute cutoffs due to assay variability 1
Ignoring vitamin D status - Low vitamin D can cause secondary hyperparathyroidism even with normal calcium
Not considering kidney function - CKD affects PTH metabolism and interpretation of results
Using different PTH assays for sequential measurements - This can lead to misinterpretation of trends
Overlooking alkaline phosphatase - The predictive power of PTH levels is increased by concomitant consideration of alkaline phosphatase levels 1
Special Considerations
In bariatric surgery patients, PTH may be more sensitive than calcium in detecting deficiency 1
In CKD patients, target ranges for mineral markers are difficult to achieve - only about 12.8% of dialysis patients have all markers within target ranges 5
During thyroid or parathyroid surgery, rapid PTH measurements can assess surgical success, with third-generation assays showing faster response than second-generation assays 1