What are the next steps for a patient with elevated Parathyroid Hormone (PTH) levels and normal Thyroid-Stimulating Hormone (TSH) levels?

Management of Elevated PTH with Normal TSH

For a patient with elevated Parathyroid Hormone (PTH) levels and normal Thyroid-Stimulating Hormone (TSH) levels, the next step should be to measure serum calcium levels to determine if this represents primary hyperparathyroidism, secondary hyperparathyroidism, or another condition. 1, 2

Initial Diagnostic Workup

• Measure serum calcium (total calcium corrected for albumin) and ionized calcium to determine if the patient has hypercalcemia, normocalcemia, or hypocalcemia 1
• Check serum phosphorus levels, as low phosphorus may be seen in primary hyperparathyroidism 2
• Measure 25-hydroxyvitamin D levels to rule out vitamin D deficiency as a cause of secondary hyperparathyroidism 2
• Assess renal function with serum creatinine and estimated GFR, as chronic kidney disease is a common cause of secondary hyperparathyroidism 3
• Consider 24-hour urinary calcium excretion to help differentiate causes of hyperparathyroidism 2

Management Algorithm Based on Calcium Status

If Hypercalcemia with Elevated PTH:

• This suggests primary hyperparathyroidism 1
• Additional workup should include:
  • Measurement of 24-hour urinary calcium to exclude familial hypocalciuric hypercalcemia 1
  • Parathyroid imaging (sestamibi scan, ultrasound, CT, or MRI) to localize abnormal gland(s) 3
• Consider referral for surgical evaluation for parathyroidectomy, especially if:
  • Patient has symptoms (nephrolithiasis, bone pain, fractures)
  • Serum calcium >1 mg/dL above upper limit of normal
  • Evidence of decreased bone mineral density
  • Age <50 years 1

If Normocalcemia with Elevated PTH:

• Rule out causes of secondary hyperparathyroidism:
  • Vitamin D deficiency (most common cause)
  • Very low calcium intake
  • Medications (lithium, thiazides, antiresorptive therapies)
  • Renal calcium leak (hypercalciuria)
  • Malabsorption syndromes 2
• If no cause of secondary hyperparathyroidism is identified, consider normocalcemic primary hyperparathyroidism 2
• A calcium load test may help differentiate normocalcemic primary hyperparathyroidism from secondary causes 2

If Hypocalcemia with Elevated PTH:

• This represents appropriate secondary hyperparathyroidism 4
• Treatment should focus on the underlying cause:
  • For vitamin D deficiency: Supplement with vitamin D (cholecalciferol or ergocalciferol) 3
  • For chronic kidney disease: Consider active vitamin D analogs (calcitriol or alfacalcidol) and phosphate binders 3

Management of Secondary Hyperparathyroidism in Chronic Kidney Disease

• For patients with CKD and elevated PTH:
  • Initial treatment includes phosphate restriction and phosphate binders 3
  • If PTH remains elevated, consider active vitamin D sterols (calcitriol or alfacalcidol) 3
  • Monitor calcium levels closely when initiating vitamin D therapy 3
  • If PTH remains elevated despite vitamin D therapy, consider calcimimetics (cinacalcet) 5
  • Cinacalcet starting dose is 30 mg once daily, titrated every 2-4 weeks based on PTH levels 5
  • Parathyroidectomy should be considered for tertiary hyperparathyroidism (persistent hypercalcemic hyperparathyroidism) 3

Special Considerations

• PTH levels between 100-500 pg/mL in CKD patients may be difficult to interpret; consider bone biopsy if there is unexplained hypercalcemia, bone pain, or increased bone alkaline phosphatase 3
• Cinacalcet is contraindicated if serum calcium is below the lower limit of normal 5
• When starting thyroid hormone replacement in patients with both thyroid and parathyroid abnormalities, ensure adequate calcium levels first to prevent hypocalcemia 3
• PTHrP (parathyroid hormone-related peptide) testing should be considered if PTH is suppressed (<26 ng/L) in the setting of hypercalcemia to evaluate for malignancy-related hypercalcemia 6

Monitoring

• For patients with primary hyperparathyroidism: Monitor serum calcium every 2 months 5
• For patients with secondary hyperparathyroidism on treatment: Monitor calcium, phosphorus, and PTH levels regularly 3
• For patients on cinacalcet: Monitor serum calcium within 1 week after initiation or dose adjustment 5
• For patients with CKD on dialysis: Monitor serum calcium approximately monthly 5