What is the diagnostic workup for secondary hyperparathyroidism?

Diagnostic Workup for Secondary Hyperparathyroidism

The diagnostic workup for secondary hyperparathyroidism requires simultaneous measurement of serum calcium and intact parathyroid hormone (iPTH), along with assessment of renal function, vitamin D status, and phosphorus levels to identify the underlying cause. 1

Initial Laboratory Evaluation

• Simultaneous measurement of serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH) is essential for accurate diagnosis 1
• Serum phosphorus measurement is critical as hyperphosphatemia is a common cause of secondary hyperparathyroidism, especially in chronic kidney disease 2
• 25-hydroxyvitamin D level should be assessed, as vitamin D deficiency is a frequent cause of secondary hyperparathyroidism 1, 3
• Renal function tests (serum creatinine, estimated glomerular filtration rate) are necessary to evaluate for chronic kidney disease 2, 4
• Serum albumin measurement for correction of total calcium values 1

Differential Diagnosis Parameters

• Secondary hyperparathyroidism is characterized by normal or low serum calcium with elevated PTH, often seen in chronic kidney disease, vitamin D deficiency, and malabsorption syndromes 1
• In patients with chronic kidney disease, iPTH levels are often persistently greater than 2-9 times the upper limit of normal 2
• Calcium-to-creatinine clearance ratio can help differentiate from primary hyperparathyroidism 1

Additional Testing Based on Clinical Context

• For patients with chronic kidney disease:

  • Calcium-phosphorus product calculation (Ca × P) is important, as values >70 mg²/dL² indicate increased risk of extraskeletal calcification 5, 4
  • Alkaline phosphatase measurement to assess bone turnover 5
  • Assessment for symptoms of renal osteodystrophy, calciphylaxis, bone/joint pain, and pathological fractures 5

• For patients with normal renal function:

  • Evaluation of intestinal absorption with calcium challenge test (oral calcium 600 mg twice daily with reassessment of iPTH after 2-3 weeks) can confirm secondary hyperparathyroidism due to insufficient calcium intake or absorption 3
  • 24-hour urinary calcium excretion to assess for hypercalciuria 1

Imaging Studies

• Imaging studies are not typically required for diagnosis of secondary hyperparathyroidism but may be needed if parathyroidectomy is being considered 1
• When surgical intervention is planned, the following may be indicated:
  • Ultrasound of the neck as the first-line localization study 1
  • Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT (parathyroid scan) for localizing parathyroid hyperplasia 1
  • MRI or CT scan if initial imaging is negative 1

Common Pitfalls to Avoid

• Not assessing vitamin D status can complicate the interpretation of PTH levels, as vitamin D deficiency is a common cause of secondary hyperparathyroidism 1
• Using different PTH assay generations without considering their varying sensitivity to PTH fragments can affect clinical decisions 5
• Failure to correct total calcium for albumin can lead to misdiagnosis 1
• Not recognizing that iPTH levels should be assessed no earlier than 12 hours after dosing with calcimimetics like cinacalcet 6
• Overlooking the possibility of tertiary hyperparathyroidism in patients with long-standing secondary hyperparathyroidism, particularly in end-stage renal disease 1

Monitoring Recommendations

• For patients with chronic kidney disease on dialysis, serum calcium and phosphorus should be measured within 1 week and iPTH should be measured 1 to 4 weeks after initiation or dose adjustment of treatment 6
• Once maintenance treatment is established, serum calcium should be measured approximately monthly for patients with secondary hyperparathyroidism with CKD on dialysis 6
• Regular monitoring of iPTH, calcium, phosphorus, and vitamin D levels is necessary to assess treatment efficacy and prevent complications 2