What laboratory tests or medications are administered to confirm primary hyperparathyroidism?

Diagnosing Primary Hyperparathyroidism

To confirm primary hyperparathyroidism, you must simultaneously measure serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH), with the hallmark finding being hypercalcemia or high-normal calcium with elevated or inappropriately normal PTH levels. 1

Essential Diagnostic Tests

• Measure serum calcium (total calcium corrected for albumin) and intact parathyroid hormone (iPTH) simultaneously as the primary diagnostic test 1, 2
• Check serum phosphate levels, which are typically low or low-normal in primary hyperparathyroidism 1
• Assess vitamin D status (25-hydroxyvitamin D) as vitamin D deficiency can complicate interpretation of PTH levels 1, 3
• Measure serum creatinine to evaluate kidney function, which is essential in diagnosing primary hyperparathyroidism 1
• Check serum chloride levels to help with differential diagnosis 1, 4

Confirmatory Testing

• Obtain a 24-hour urine collection for calcium, oxalate, uric acid, citrate, sodium, potassium, and creatinine to evaluate complications and other metabolic abnormalities 1
• Calculate calcium-to-creatinine clearance ratio; a ratio <0.01 suggests familial hypocalciuric hypercalcemia rather than primary hyperparathyroidism 4
• Consider measuring 1,25-dihydroxyvitamin D levels, which are often elevated in primary hyperparathyroidism 4, 5

Interpretation of Results

• Primary hyperparathyroidism is confirmed by demonstrating persistent hypercalcemia (or normal-high serum calcium) with inappropriately normal or elevated iPTH 4
• Be aware that approximately 3% of patients with primary hyperparathyroidism may have both calcium and PTH within the reference range 6
• Different presentations of primary hyperparathyroidism include:
  • Classic presentation (70%): Concomitant elevation of both calcium (≥10.5 mg/dL) and PTH (≥65 pg/dL) 6
  • Normocalcemic hyperparathyroidism (21%): Normal calcium (≤10.5 mg/dL) with elevated PTH (≥65 pg/dL) 6
  • Normohormonal hyperparathyroidism (6%): Elevated calcium (≥10.5 mg/dL) with normal PTH (≤65 pg/dL) 6

Important Considerations

• Use assay-specific reference values for PTH measurement, as different assay generations can affect clinical interpretation 3
• Be aware that PTH assays differ in the antibodies used and consequently measure different PTH fragments and isoforms in addition to biologically active PTH 3
• Standardization of PTH assays is ongoing, and lack of standardization leads to significant differences in PTH concentrations measured in different laboratories 3
• Collect blood samples in EDTA tubes for PTH measurement as PTH is most stable in EDTA plasma 3
• Consider factors that influence PTH levels such as race, age, BMI, and vitamin D status when interpreting results 3

Differential Diagnosis

• Secondary hyperparathyroidism: Normal or low serum calcium with elevated PTH, commonly seen in chronic kidney disease or vitamin D deficiency 1, 2
• Tertiary hyperparathyroidism: Hypercalcemia with elevated PTH, typically in end-stage renal disease 1, 2
• Familial hypocalciuric hypercalcemia: Hypercalcemia with hypocalciuria (calcium-to-creatinine clearance ratio <0.01) 4
• Non-parathyroid causes of hypercalcemia: Malignancy, granulomatous diseases, vitamin D intoxication, or medications (check for suppressed PTH) 4, 5
• Rare cases of parathyroid adenomas producing PTHrP with hypercalcemia but normal PTH levels 7

Next Steps After Biochemical Diagnosis

• If primary hyperparathyroidism is confirmed, seek advice from a specialist with expertise in this condition 3, 1
• Imaging studies should only be performed after biochemical confirmation of primary hyperparathyroidism 1, 4
• Ultrasound of the neck is recommended as the first-line localization study 1, 2
• Dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT provides high sensitivity for localizing parathyroid adenomas 1, 2

Common Pitfalls to Avoid

• Not measuring vitamin D status when interpreting PTH levels can lead to misdiagnosis 1, 3
• Using different PTH assay generations without considering their varying sensitivity to PTH fragments can result in inaccurate diagnoses 3, 2
• Failing to recognize atypical presentations of primary hyperparathyroidism, such as normocalcemic or normohormonal variants 6, 5
• Not considering biotin supplements, which can interfere with PTH assays and lead to under or overestimation depending on the assay design 3