What lab values indicate primary hyperparathyroidism?

Laboratory Values Indicating Primary Hyperparathyroidism

The hallmark laboratory finding in primary hyperparathyroidism is hypercalcemia (or high-normal calcium) with an elevated or inappropriately normal parathyroid hormone (PTH) level—a PTH that is not suppressed despite elevated calcium is diagnostic. 1, 2

Essential Diagnostic Laboratory Panel

Core Biochemical Findings

• Serum calcium (corrected for albumin): Elevated above 10.3 mg/dL or high-normal range 3

  • Corrected calcium >0.25 mmol/L (approximately 1 mg/dL) above the upper limit of normal indicates more severe disease 3
  • In healthy individuals, any hypercalcemia from non-parathyroid causes should suppress PTH to undetectable or very low levels 2

• Intact parathyroid hormone (iPTH): Elevated or inappropriately normal (not suppressed) in the presence of hypercalcemia 1, 2

  • A "normal" PTH in the presence of elevated calcium is physiologically inappropriate and diagnostic of primary hyperparathyroidism 2
  • The parathyroid glands autonomously secrete PTH despite elevated calcium 3

• Serum phosphate: Typically low or low-normal 1, 3

Additional Required Laboratory Tests

• 25-hydroxyvitamin D: Must be measured to exclude vitamin D deficiency as a cause of secondary hyperparathyroidism 1, 2

  • Vitamin D deficiency causes secondary hyperparathyroidism and must be excluded before diagnosing primary hyperparathyroidism 3
  • PTH reference values are 20% lower in vitamin D-replete individuals compared to those with unknown vitamin D status 3

• Serum creatinine and estimated GFR: Essential to evaluate kidney function 1, 3

  • Impaired kidney function (GFR <60 mL/min/1.73 m²) is a surgical indication in confirmed primary hyperparathyroidism 3

• 24-hour urine calcium (or spot urine calcium/creatinine ratio): Evaluates for hypercalciuria and kidney stone risk 1, 3

  • Most primary hyperparathyroidism patients demonstrate hypercalciuria (>4 mg/kg/day or >250-300 mg/day) 1
  • Levels >400 mg/day indicate increased risk for kidney stone formation and bone complications 1

Atypical Presentations to Recognize

Normocalcemic Primary Hyperparathyroidism

• Calcium: Within normal range (8.6-10.3 mg/dL) 3
• PTH: Persistently elevated 1, 4
• This diagnosis should only be made after careful exclusion of all causes of secondary hyperparathyroidism 4
• These patients remain at risk for developing complications associated with classic primary hyperparathyroidism 5

Normohormonal Primary Hyperparathyroidism

• Calcium: Elevated (≥10.5 mg/dL) 6
• PTH: Within reference range but inappropriately normal for the degree of hypercalcemia 6
• Represents approximately 6% of primary hyperparathyroidism cases 6

Critical Technical Considerations for PTH Measurement

Pre-analytical Factors

• Sample collection: Use EDTA plasma rather than serum, as PTH is most stable in EDTA plasma 5, 3
• Storage: PTH is more stable at 4°C than at room temperature 5
• Sampling site: PTH concentrations are higher in central blood than peripheral blood 5
• Timing: PTH has a circadian rhythm, though optimal sampling time is not definitively established 5

Analytical Factors

• Assay variability: PTH measurements can vary up to 47% between different assay generations 3
• Use assay-specific reference values: Different assays measure different PTH fragments and isoforms in addition to biologically active PTH 1, 3
• Biological variation: PTH variation is substantial (20% in healthy individuals), so differences must exceed 54% to be clinically significant 3
• Biotin interference: Biotin supplements can interfere with PTH assays and lead to under or overestimation depending on assay design 1

Factors Influencing PTH Reference Values

• Age: PTH levels increase with age due to decreased glomerular filtration rate 1
• Race: Higher PTH levels are found in Black individuals 1
• BMI: Elevated body mass index increases PTH levels 1
• Vitamin D status: PTH levels are 20% lower in individuals with sufficient vitamin D 1

Common Diagnostic Pitfalls to Avoid

• Not assessing vitamin D status: Vitamin D deficiency can complicate interpretation of PTH levels and lead to misdiagnosis 1
• Ignoring assay-specific reference ranges: Using different PTH assay generations without considering their varying sensitivity to PTH fragments can result in inaccurate diagnoses 1
• Vitamin D deficiency masking hypercalciuria: Vitamin D deficiency can suppress urine calcium excretion in primary hyperparathyroidism patients, potentially masking hypercalciuria 1
• Ordering imaging before biochemical confirmation: Imaging has no utility in confirming or excluding the diagnosis of hyperparathyroidism; it is used only for localization after biochemical diagnosis is established 1