Why Check a Parathyroid Hormone (PTH) Level
You should check a PTH level to evaluate calcium disorders, screen for bone and mineral metabolism abnormalities in chronic kidney disease, and differentiate between various causes of hypercalcemia or hypocalcemia.
Primary Clinical Indications for PTH Testing
Evaluation of Abnormal Calcium Levels
Measure serum calcium and intact PTH simultaneously when investigating any calcium abnormality, as this combination is essential for accurate diagnosis 1, 2.
In hypercalcemia, PTH distinguishes PTH-dependent from PTH-independent causes: an elevated or inappropriately normal PTH indicates primary hyperparathyroidism, while a suppressed PTH (<20 pg/mL) points toward malignancy, granulomatous disease, vitamin D intoxication, or other non-parathyroid causes 3.
In hypocalcemia, PTH helps differentiate hypoparathyroidism (low PTH) from secondary hyperparathyroidism (elevated PTH) due to vitamin D deficiency, malabsorption, or chronic kidney disease 4, 5.
Chronic Kidney Disease Monitoring
Check PTH in all patients with CKD when GFR falls below 60 mL/min/1.73 m², as bone and mineral metabolism disorders begin when approximately 50% of kidney function is lost 6.
The frequency of PTH monitoring should be based on CKD stage: more frequent testing is needed as kidney disease progresses and when patients receive treatment for calcium, phosphorus, or PTH abnormalities 6.
PTH screening in CKD prevents high-turnover bone disease (osteitis fibrosa) and identifies low-turnover bone disorders (adynamic bone disease), which affect nearly all patients by the time they require dialysis 6.
Specific Clinical Scenarios Requiring PTH Assessment
Evaluate PTH in patients with:
Nephrolithiasis or nephrocalcinosis, as primary hyperparathyroidism is a common underlying cause 7.
Osteoporosis or osteopenia on DEXA scan, particularly when bone loss seems disproportionate to age and risk factors 7.
Bone pain, pathologic fractures, or subperiosteal resorption, which may indicate severe hyperparathyroidism 7.
Personal history of neck irradiation or family history of multiple endocrine neoplasia (MEN) syndromes, as these increase risk for primary hyperparathyroidism 7, 1.
Differential Diagnosis Using PTH
PTH levels help distinguish between hyperparathyroid conditions:
Primary hyperparathyroidism: hypercalcemia (or high-normal calcium) with elevated or inappropriately normal PTH 1, 2.
Secondary hyperparathyroidism: normal or low calcium with elevated PTH, commonly seen in CKD, vitamin D deficiency, or malabsorption 2, 4.
Tertiary hyperparathyroidism: hypercalcemia with elevated PTH, typically in end-stage renal disease 1, 2.
Malignancy-Related Hypercalcemia
- When hypercalcemia occurs with suppressed PTH, consider measuring PTH-related peptide (PTHrP) to identify humoral hypercalcemia of malignancy, where tumors secrete PTHrP that mimics PTH action 8.
Essential Complementary Testing
Always assess vitamin D status (25-hydroxyvitamin D) when checking PTH, as vitamin D deficiency can cause secondary hyperparathyroidism and complicate interpretation of PTH levels 1, 2.
Measure serum phosphate alongside PTH and calcium: phosphate is typically low or low-normal in primary hyperparathyroidism but elevated in CKD-related secondary hyperparathyroidism 1, 6.
Check serum creatinine to evaluate kidney function, as renal impairment fundamentally alters PTH metabolism and interpretation 1, 8.
Important Caveats and Pitfalls
Use assay-specific reference values for PTH measurement, as different assay generations (intact PTH vs. whole PTH) measure different PTH fragments and can significantly affect clinical interpretation 1, 2.
Collect blood samples in EDTA tubes for PTH measurement, as PTH is most stable in EDTA plasma 1, 8.
Be aware that biotin supplements can interfere with PTH assays, potentially causing falsely elevated or decreased results depending on the assay design 8, 1.
Consider that kidney function inversely affects PTH levels, with an inverse relationship between eGFR and PTH concentration 8.
PTH has substantial biological variation (~20% within-subject variation), so borderline results may require repeat testing 8.