What is the appropriate workup and management for a patient with elevated Parathyroid Hormone (PTH) levels, potentially indicating primary or secondary hyperparathyroidism, with possible underlying kidney disease and impaired renal function?

Workup of Elevated PTH

Begin by measuring serum calcium, phosphorus, 25-OH vitamin D, and kidney function (eGFR/creatinine) to distinguish primary from secondary hyperparathyroidism and identify the underlying cause. 1, 2

Initial Laboratory Assessment

The calcium level is the critical discriminator:

• Elevated or high-normal calcium with elevated PTH indicates primary hyperparathyroidism (PHPT), typically from parathyroid adenoma or hyperplasia 3, 2
• Low or low-normal calcium with elevated PTH suggests secondary hyperparathyroidism from vitamin D deficiency, CKD, or malabsorption 2, 4
• Normal calcium with elevated PTH requires further evaluation to differentiate normocalcemic PHPT from secondary causes 4

Essential Initial Tests

• Serum calcium (total and ionized if available) 1, 2
• Serum phosphorus - low in PHPT, elevated in CKD-related secondary hyperparathyroidism 1, 2
• 25-OH vitamin D - deficiency (<30 ng/mL) is the most common reversible cause of secondary hyperparathyroidism 1, 2
• Kidney function (eGFR, creatinine) - PTH rises early in CKD, often before calcium/phosphorus abnormalities appear 1, 2

Additional Considerations

• Review medications that affect calcium metabolism (lithium, thiazides, antiresorptive therapies) 1, 4
• Assess for malabsorption or gastrointestinal disorders 4
• Check 24-hour urine calcium - helps identify renal calcium leak causing secondary hyperparathyroidism 4

Interpretation Based on PTH Assay Generation

PTH assay differences matter in specific contexts:

• For PHPT diagnosis: Second- and third-generation assays have similar diagnostic sensitivity; the precise PTH value is less critical since hypercalcemia with inappropriately elevated/normal PTH establishes the diagnosis 3
• For CKD patients: PTH reference ranges vary by assay generation, affecting treatment thresholds 3
• Important caveat: PTH is higher in Black individuals, increases with age and BMI, and rises with declining GFR 3

Management Algorithm by Underlying Cause

Vitamin D Deficiency (25-OH vitamin D <30 ng/mL)

• Supplement with cholecalciferol or ergocalciferol to achieve levels ≥30 ng/mL 1, 2
• Recheck PTH every 3 months for 6 months, then every 3-6 months thereafter 1, 5
• Monitor calcium and phosphorus monthly for first 3 months, then every 3 months 1, 5

Primary Hyperparathyroidism (Hypercalcemia + Elevated PTH)

Parathyroidectomy is indicated for: 3, 1

• Symptomatic patients
• Osteoporosis
• Impaired kidney function (GFR <60 mL/min/1.73 m²)
• Kidney stones or hypercalciuria
• Age ≥50 years
• Calcium >0.25 mmol/L above upper limit of normal

CKD-Related Secondary Hyperparathyroidism

Target PTH levels in CKD: 3

• Do NOT maintain PTH in the normal range (<65 pg/mL) - this causes adynamic bone disease 3, 2
• Desired target range: 150-300 pg/mL for dialysis patients 3
• PTH levels 100-500 pg/mL have insufficient sensitivity/specificity to predict bone disease 1, 2

Medical management: 3, 1, 5

• Control serum phosphorus: 3.5-5.5 mg/dL in Stage 5 CKD/dialysis patients 3
• Dietary phosphate restriction and phosphate binders if hyperphosphatemia present 1, 5
• Low-dose active vitamin D as supplement to nutritional vitamin D 1
• Avoid active vitamin D if phosphorus >6.5 mg/dL due to risk of further elevation 2

Surgical indications: 1, 5

• PTH persistently >800 pg/mL with hypercalcemia/hyperphosphatemia refractory to medical therapy 1, 5
• Options: subtotal parathyroidectomy or total parathyroidectomy with autotransplantation 1, 5
• For PTH 100-500 pg/mL: bone biopsy may be needed before surgery to document hyperparathyroid bone disease 1

Normocalcemic Elevated PTH

If all secondary causes excluded:

• Consider normocalcemic PHPT 4
• Calcium load test can help - PTH should suppress appropriately when calcium rises above normal 4
• Thiazide challenge test may differentiate renal calcium leak from normocalcemic PHPT in patients with hypercalciuria 4

Critical Pitfalls to Avoid

• Do not assume PTH elevation alone indicates PHPT - calcium level is essential for proper classification 2
• Do not over-suppress PTH in CKD patients - intact PTH <150 pg/mL associated with adynamic bone disease 2
• Do not delay surgery in PHPT patients with recurrent kidney stones - progressive renal damage can occur 1
• Recognize that many "intact PTH" assays detect biologically inactive fragments (amino acids 7-84), leading to spuriously elevated levels in CKD 3
• Be cautious with calcimimetics in elderly patients - cinacalcet can cause severe hypocalcemia and QT prolongation 2

Post-Parathyroidectomy Monitoring

• Monitor ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 1, 5
• Adjust phosphate binders based on post-operative phosphorus levels 5
• Watch for hungry bone syndrome - may require intensive calcium and vitamin D supplementation 6