What is the initial workup for hyperparathyroidism?

Workup for Hyperparathyroidism

Measure serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH) simultaneously—this is the cornerstone of diagnosis and should be your first step. 1, 2

Initial Laboratory Tests

The biochemical diagnosis requires these specific measurements:

• Serum calcium (corrected for albumin) and iPTH measured together to establish the diagnosis—hypercalcemia or high-normal calcium with elevated or inappropriately normal PTH confirms primary hyperparathyroidism 1, 2
• Serum phosphate should be measured as it is typically low or low-normal in primary hyperparathyroidism 3, 2
• 25-hydroxyvitamin D levels must be checked because vitamin D deficiency can elevate PTH and complicate interpretation—this is a critical step that is often missed 1, 3, 2
• Serum creatinine to evaluate kidney function, as chronic kidney disease causes secondary hyperparathyroidism and affects management 2, 4

Additional Diagnostic Tests

Once the initial workup suggests hyperparathyroidism, obtain:

• 24-hour urine collection for calcium, creatinine, oxalate, uric acid, citrate, sodium, and potassium to evaluate complications and rule out familial hypocalciuric hypercalcemia (FHH) 2, 5
• Serum chloride as it may be elevated in primary hyperparathyroidism 5, 6
• 1,25-dihydroxyvitamin D for differential diagnosis when needed 5, 6

Critical Interpretation Points

Primary hyperparathyroidism: Elevated or inappropriately normal PTH with hypercalcemia or high-normal calcium 2, 5, 6

Secondary hyperparathyroidism: Elevated PTH with normal or low calcium, typically from chronic kidney disease or vitamin D deficiency 1, 4, 7

Tertiary hyperparathyroidism: Elevated PTH with hypercalcemia in patients with end-stage renal disease or after prolonged secondary hyperparathyroidism 1, 7

Familial hypocalciuric hypercalcemia (FHH): If calcium-to-creatinine clearance ratio is <0.01, consider FHH rather than primary hyperparathyroidism 5

Imaging Studies (After Biochemical Diagnosis)

Imaging is for localization only, not diagnosis:

• Neck ultrasound as the first-line localization study 1, 2
• Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT provides high sensitivity for localizing adenomas 1, 2
• Combination of ultrasound and sestamibi scan offers the highest sensitivity 1, 2
• MRI or CT may be considered if initial imaging is negative or for reoperative cases 1, 2

Common Pitfalls to Avoid

• Not measuring vitamin D status is the most common error—vitamin D deficiency can cause secondary hyperparathyroidism and must be excluded 1, 3, 2
• Using different PTH assay generations without considering their varying sensitivity to PTH fragments can lead to misinterpretation—use assay-specific reference ranges 8, 1, 3, 2
• Biotin supplements can interfere with PTH assays and cause falsely elevated or decreased results 3, 2
• Ordering imaging before biochemical confirmation—imaging is for localization after diagnosis is established, not for diagnosis itself 5
• Collecting blood in the wrong tube—use EDTA tubes for PTH measurement as PTH is most stable in EDTA plasma 2

Special Clinical Scenarios

• Patients with chronic kidney disease: Different diagnostic criteria apply—secondary hyperparathyroidism is characterized by elevated PTH with normal or low calcium 1, 4, 7
• Suspected MEN syndromes: Screen for primary hyperparathyroidism starting at age 11 for high-risk variants and age 16 for moderate-risk variants 1, 2
• Clinical red flags requiring evaluation: Nephrolithiasis, nephrocalcinosis, bone pain, pathologic fractures, osteoporosis on DEXA, personal history of neck irradiation, or family history of MEN syndromes 4, 5, 6