When should parathyroid hormone (PTH) levels be checked?

When to Check PTH Levels

PTH levels should be measured in all patients with chronic kidney disease when GFR falls below 60 mL/min/1.73 m² (CKD Stage 3 or higher), with frequency determined by CKD stage and treatment status. 1

Primary Indications for Initial PTH Measurement

In Chronic Kidney Disease

• Measure PTH when GFR <60 mL/min/1.73 m² along with serum calcium and phosphorus to screen for secondary hyperparathyroidism, as PTH levels begin rising at this threshold and bone disease may already be present. 1

When Evaluating Hypercalcemia

• Measure PTH simultaneously with serum calcium (corrected for albumin) when hypercalcemia is detected to distinguish primary hyperparathyroidism from other causes. 2, 3
• The combination of elevated calcium with elevated or inappropriately normal PTH confirms primary hyperparathyroidism. 3

Additional Clinical Scenarios

• Measure PTH when evaluating unexplained bone pain, pathological fractures, or kidney stones. 1, 4
• Check PTH in patients with vitamin D deficiency to assess for secondary hyperparathyroidism. 2, 3
• Measure PTH when assessing kidney function decline (rising creatinine) to detect early mineral bone disorder. 3

Monitoring Frequency by CKD Stage

The frequency of PTH monitoring increases as kidney function declines: 1

• CKD Stage 3 (GFR 30-59): Measure every 12 months
• CKD Stage 4 (GFR 15-29): Measure every 3 months
• CKD Stage 5 (GFR <15 or dialysis): Measure every 3 months

During Active Treatment

• Measure monthly for the first 3 months after initiating therapy for abnormal calcium, phosphorus, or PTH levels. 2
• After stabilization, measure every 3 months. 2
• Patients with PTH at the low end of target range may be monitored less frequently. 1

Important Technical Considerations

Sample Collection and Timing

• Collect blood in EDTA tubes rather than serum, as PTH is most stable in EDTA plasma. 3
• Store samples at 4°C if not immediately processed. 3
• Be aware that PTH has circadian variation, though optimal sampling time is not definitively established. 3

Assay Interpretation Pitfalls

• Use assay-specific reference ranges, as different PTH assay generations measure different PTH fragments and yield significantly different values. 2, 3, 5
• Second-generation "intact PTH" assays (current standard) measure both biologically active PTH and inactive fragments, which accumulate in CKD and can overestimate true PTH activity. 1, 5
• Biotin supplements can interfere with PTH assays, causing falsely elevated or decreased results depending on assay design. 2, 3

Factors Affecting PTH Levels

• Vitamin D deficiency elevates PTH and must be assessed (measure 25-hydroxyvitamin D) to properly interpret PTH results. 2, 3
• PTH increases with age due to declining GFR. 3
• PTH levels are 20% higher in Black individuals compared to other races. 2, 3
• Elevated BMI increases PTH levels. 2, 3

Special Clinical Situations

When PTH is Between 100-500 pg/mL in CKD Stage 5

This range has insufficient sensitivity to distinguish adynamic bone disease from hyperparathyroidism. 1

Consider bone biopsy if the patient develops: 1

• Unexplained hypercalcemia
• Severe bone pain
• Unexplained increases in bone alkaline phosphatase

In Kidney Transplant Recipients

• Monitor calcium, phosphorus, and PTH more frequently as specified in transplant-specific protocols. 1
• Tertiary hyperparathyroidism (hypercalcemia with elevated PTH) may persist post-transplant. 3

Screening for Multiple Endocrine Neoplasia (MEN)

• Begin screening at age 11 for high-risk MEN variants and age 16 for moderate-risk variants. 3
• Family members of patients with MEN syndromes warrant genetic testing and PTH screening. 4

Common Clinical Pitfalls to Avoid

• Do not interpret PTH without checking vitamin D status, as deficiency can mask or exacerbate hyperparathyroidism. 2, 3
• Do not rely on PTH alone in CKD patients with levels in the intermediate range (100-500 pg/mL in Stage 5), as significant bone disease may be present despite "acceptable" PTH values. 1, 5
• Do not assume all PTH assays are equivalent—lack of standardization between laboratories can lead to significantly different measured concentrations. 3, 5
• Be aware that PTH has high biological variability (coefficient of variation 25.6% in hemodialysis patients), requiring multiple measurements to accurately estimate an individual's homeostatic set point. 6