What is the further workup for a patient with high Parathyroid Hormone (PTH) levels?

Workup for Elevated Parathyroid Hormone (PTH) Levels

The comprehensive workup for elevated PTH should include serum calcium, phosphorus, 25-hydroxyvitamin D, renal function tests, and imaging studies to determine the underlying cause, with bone biopsy reserved for specific indications when non-invasive tests are inconclusive. 1

Initial Laboratory Evaluation

• Serum calcium: Critical first step to differentiate primary from secondary hyperparathyroidism

  • Normal/high calcium with high PTH suggests primary hyperparathyroidism
  • Low/normal calcium with high PTH suggests secondary hyperparathyroidism

• Additional essential labs:

  • Serum phosphorus (typically low in primary, high in secondary hyperparathyroidism)
  • 25-hydroxyvitamin D (to rule out vitamin D deficiency)
  • Renal function tests (creatinine, eGFR)
  • Alkaline phosphatase (to assess bone turnover)
  • 24-hour urinary calcium (to assess for hypercalciuria)
  • Chloride-to-phosphate ratio (elevated >33 suggests primary hyperparathyroidism)

Secondary Testing Based on Initial Results

If calcium is elevated or high-normal with elevated PTH:

• Focused parathyroid imaging:
  • Sestamibi scan with SPECT/CT
  • Ultrasound of the neck
  • 4D-CT scan if conventional imaging is negative

If calcium is normal/low with elevated PTH:

• Check for secondary causes:
  • Comprehensive CKD-MBD panel if renal dysfunction is present 1
  • 1,25-dihydroxyvitamin D levels
  • Magnesium levels (hypomagnesemia can cause PTH resistance)
  • Gastrointestinal absorption studies if malabsorption is suspected

If results are equivocal:

• Consider assay interference:
  • Repeat PTH measurement using a different assay 2
  • Polyethylene glycol precipitation test to rule out macro-PTH

Advanced Testing in Specific Scenarios

For patients with CKD:

• If PTH is between 100-500 pg/mL with unexplained hypercalcemia, bone pain, or increased bone alkaline phosphatase:
  • Consider bone biopsy to differentiate between adynamic bone disease and hyperparathyroidism 3
  • Bone biopsy should be performed after tetracycline labeling from the anterior iliac crest

For suspected tertiary hyperparathyroidism:

• Monitor calcium levels after renal transplantation
• Consider parathyroidectomy for persistent hypercalcemic hyperparathyroidism despite optimized medical therapy 4

For familial forms:

• Genetic testing for MEN1, MEN2, or other hereditary syndromes if there is family history of hyperparathyroidism 5

Management Considerations Based on Diagnosis

For primary hyperparathyroidism:

• Surgical consultation for parathyroidectomy if symptomatic or meeting surgical criteria
• Medical management with cinacalcet for non-surgical candidates 6

For secondary hyperparathyroidism in CKD:

• Manage with active vitamin D and/or decreasing oral phosphate supplements 3
• Consider calcimimetics (cinacalcet) for persistent secondary hyperparathyroidism 1
• Target PTH levels based on CKD stage:
  • CKD G3: <70 pg/mL
  • CKD G4: <110 pg/mL
  • CKD G5: <300 pg/mL 1

For tertiary hyperparathyroidism:

• Parathyroidectomy (total, subtotal, or limited) is the primary treatment 4

Common Pitfalls to Avoid

• Falsely elevated PTH: Consider assay interference from heterophile antibodies or macro-PTH when PTH levels don't correlate with clinical picture 2
• Overlooking vitamin D deficiency: Always check and correct vitamin D deficiency before further workup
• Premature parathyroid ablation: Any patient with PTH levels <800-1000 pg/mL may require bone biopsy prior to parathyroid ablative therapy to confirm hyperparathyroidism 3
• Ignoring aluminum toxicity: In CKD patients with history of aluminum exposure, bone biopsy should be performed before parathyroid ablation therapy 3
• Overtreatment with calcium: May increase risk of nephrocalcinosis in certain conditions 1

By following this structured approach to evaluating elevated PTH, clinicians can efficiently determine the underlying cause and implement appropriate management strategies to improve patient outcomes related to morbidity, mortality, and quality of life.