Workup for Secondary Hyperparathyroidism
Begin with measurement of intact PTH, serum calcium, serum phosphorus, and 25-hydroxyvitamin D in all patients with CKD and GFR <60 mL/min/1.73 m² to establish the diagnosis and guide treatment. 1, 2
Initial Laboratory Assessment
Measure the following baseline parameters:
- Intact PTH (iPTH) – Use second-generation "intact PTH" assay, which is the standard in most laboratories and adequate for screening 1, 3
- Serum calcium (corrected for albumin) – To identify hypocalcemia driving PTH elevation 1, 2
- Serum phosphorus – Hyperphosphatemia is a key driver of secondary hyperparathyroidism 1, 2
- 25-hydroxyvitamin D [25(OH)D] – Deficiency (<30 ng/mL) contributes to PTH elevation and requires repletion 2, 3
- Alkaline phosphatase – Elevated levels suggest high bone turnover 2
Important assay consideration: Be aware that different PTH assay generations can yield results varying by up to 47%, which affects clinical decisions particularly when using absolute cutoff values 1. Sequential measurements should always use the same assay in the same laboratory 3.
Frequency of Monitoring Based on CKD Stage
CKD Stage 3 (GFR 30-59 mL/min/1.73 m²):
CKD Stage 4 (GFR 15-29 mL/min/1.73 m²):
- Measure calcium and phosphorus every 3-6 months 1, 2
- Measure PTH every 3-6 months 1, 2
- Initiate intervention when PTH >110 pg/mL 2, 3
CKD Stage 5 (GFR <15 mL/min/1.73 m² or on dialysis):
- Measure calcium and phosphorus monthly initially, then every 1-3 months once stable 1, 2
- Measure PTH every 3 months 1, 2
- Target PTH range is 150-300 pg/mL (not normal range) 1, 2, 3
Identifying the Underlying Causes
Evaluate for the three primary drivers of secondary hyperparathyroidism:
- Hyperphosphatemia – Serum phosphorus >4.6 mg/dL in CKD stages 3-4, or >5.5 mg/dL in stage 5 1, 2
- Hypocalcemia – Corrected serum calcium <8.4 mg/dL 1, 2
- Vitamin D deficiency – 25(OH)D <30 ng/mL requires repletion with ergocalciferol 50,000 IU monthly 2
Critical pitfall: When creatinine clearance falls below 20-30 mL/min/1.73 m² (CKD Stage 4), the compensatory phosphaturic effect of PTH reaches its maximum, and serum phosphorus begins to rise despite elevated PTH 3. This represents failure of the normal homeostatic mechanism.
Additional Workup Considerations
Assess for complications of uncontrolled secondary hyperparathyroidism:
- Bone disease markers – Bone-specific alkaline phosphatase and bone turnover markers if PTH remains elevated 2
- Vascular calcification risk – Calculate calcium-phosphorus product (should be <55 mg²/dL²) 1, 3
- Imaging is NOT routinely recommended – Parathyroid imaging (ultrasound or sestamibi scan) is reserved for surgical planning in refractory cases, not for initial diagnosis 1, 4
When to Consider Advanced Workup
Indications for parathyroid imaging prior to surgery:
- PTH persistently >800 pg/mL with hypercalcemia and/or hyperphosphatemia refractory to medical therapy for 3-6 months 1, 2, 4
- Severe symptoms (intractable pruritus, calciphylaxis, pathological fractures, severe bone pain) despite optimal medical management 1
- Planning for parathyroidectomy – Use ultrasound and/or 99Tc-sestamibi scan to localize hyperplastic glands 4
Do NOT perform bone biopsy routinely – This is reserved for research settings or when diagnosis is uncertain despite biochemical workup 1.
Critical Monitoring During Treatment
Once treatment is initiated:
- Measure calcium and phosphorus within 1 week of starting therapy 2, 5
- Measure PTH 1-4 weeks after initiation or dose adjustment 5
- During vitamin D sterol therapy, monitor calcium and phosphorus every 2 weeks for 1 month, then monthly 4
- Monitor PTH monthly for at least 3 months, then every 3 months once target achieved 4
Common pitfall to avoid: Never target "normal" PTH levels (<65 pg/mL) in dialysis patients, as this causes adynamic bone disease with increased fracture risk and loss of bone buffering capacity for calcium 1, 2, 3. The appropriate target for stage 5 CKD is PTH 150-300 pg/mL 1, 2.