What should my initial workup be for Hyperparathyroidism (Hyper PTH) with mild Hypercalcemia?

Initial Workup for Hyperparathyroidism with Mild Hypercalcemia

The initial workup for hyperparathyroidism with mild hypercalcemia should include measurement of serum calcium, phosphorus, intact PTH, 25-hydroxyvitamin D, and assessment of renal function with creatinine and estimated GFR. 1

Key Laboratory Tests

• Serum calcium: Confirm hypercalcemia with repeat measurement
• Ionized calcium: More accurate reflection of physiologically active calcium
• Intact PTH: Essential to distinguish PTH-dependent from PTH-independent causes
  • Use appropriate generation assay (second or third-generation) 2
• Serum phosphorus: Typically low in primary hyperparathyroidism
• 25-hydroxyvitamin D: To rule out vitamin D deficiency as a cause of secondary hyperparathyroidism
• Renal function tests: Creatinine and estimated GFR
• 24-hour urine calcium: To differentiate primary hyperparathyroidism from familial hypocalciuric hypercalcemia
• Serum albumin: For corrected calcium calculation

Imaging Studies

After biochemical confirmation of primary hyperparathyroidism:

• Neck ultrasound: First-line imaging to locate parathyroid adenoma
• Sestamibi scan: If ultrasound is negative or inconclusive
• Bone mineral density: To assess for skeletal involvement (particularly at distal radius, lumbar spine, and hip)
• Renal imaging: To evaluate for nephrolithiasis or nephrocalcinosis if clinically indicated

Diagnostic Algorithm

1. Confirm hypercalcemia with repeat measurement
2. Measure intact PTH:
   • Elevated or inappropriately normal PTH with hypercalcemia suggests primary hyperparathyroidism
   • Suppressed PTH (<20 pg/mL) suggests non-PTH mediated hypercalcemia (malignancy, granulomatous disease, etc.) 1
3. Assess vitamin D status to rule out vitamin D deficiency
4. Calculate fractional excretion of calcium using 24-hour urine calcium and creatinine
   • Low urinary calcium (<100 mg/24h) suggests familial hypocalciuric hypercalcemia
   • High urinary calcium (>250 mg/24h) is typical of primary hyperparathyroidism

Common Pitfalls to Avoid

• Not repeating calcium measurement: Single elevated calcium value may be spurious
• Ignoring vitamin D status: Vitamin D deficiency can mask the severity of primary hyperparathyroidism
• Using incorrect PTH assay: Different generations of PTH assays measure different fragments, affecting interpretation 2
• Failing to calculate urinary calcium excretion: Essential to rule out familial hypocalciuric hypercalcemia
• Not considering medication effects: Thiazide diuretics, lithium, and calcium/vitamin D supplements can affect calcium levels 1

Target Values and Monitoring

For patients with confirmed primary hyperparathyroidism:

• Target PTH levels vary by CKD stage:
  • CKD G3: <70 pg/mL
  • CKD G4: <110 pg/mL
  • CKD G5: <300 pg/mL
  • CKD G5D: 150-600 pg/mL 3

For mild asymptomatic hyperparathyroidism, monitoring should occur every 3-6 months initially, then every 6-12 months once stable, to assess calcium, phosphorus, and PTH levels and to monitor for complications such as bone disease, kidney stones, and cardiovascular calcifications 3.