What 24‑hour urine calcium excretion is normal in adults and what level supports primary hyperparathyroidism versus familial hypocalciuric hypercalcemia?

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24-Hour Urine Calcium in Hyperparathyroidism

Normal 24-hour urine calcium excretion in adults is <250 mg/day (6.2 mmol/day) in females and <4 mg/kg/day (0.1 mmol/kg/day) for all adults, while primary hyperparathyroidism typically shows hypercalciuria (>250-300 mg/day), and familial hypocalciuric hypercalcemia characteristically demonstrates low urinary calcium (<100 mg/24hr or <2.5 mmol/24hr). 1

Normal Reference Ranges

  • 24-hour urinary calcium excretion in healthy adults is typically <250 mg/day (6.2 mmol/day) in females and <4 mg/kg/day (0.1 mmol/kg/day) for all adults 1

  • The collection must be performed on a random diet with proper acidification to prevent calcium precipitation 1

  • Creatinine measurement is essential to verify collection completeness 1

Primary Hyperparathyroidism (PHPT) Pattern

Most PHPT patients demonstrate hypercalciuria due to the increased filtered calcium load from hypercalcemia 2:

  • Typical 24-hour urine calcium: >250-300 mg/day (>6.2-7.5 mmol/day) 2

  • Urine calcium >400 mg/day identifies patients at increased risk for kidney stones and bone complications, and serves as a surgical indication for parathyroidectomy 2

  • In one surgical series, median 24-hour urine calcium in PHPT was 8.3 mmol/24hr (range 5.6-11.2), significantly higher than FHH 3

Important Caveat

  • Vitamin D deficiency can suppress urine calcium excretion in PHPT patients, potentially masking hypercalciuria and creating diagnostic confusion 2

  • Ensure 25-hydroxyvitamin D ≥50 nmol/L (≥20 ng/mL) before interpreting urinary calcium results 2, 4

Familial Hypocalciuric Hypercalcemia (FHH) Pattern

FHH characteristically shows inappropriately low urinary calcium despite hypercalcemia 2:

  • Typical 24-hour urine calcium: <100 mg/day (<2.5 mmol/day) 5, 3

  • In genetically confirmed FHH, median 24-hour urine calcium was 3.2 mmol/24hr (range 2.1-6.1), markedly lower than PHPT 3

  • Mean urinary calcium excretion in FHH: 6.6 ± 5.4 mEq/day versus 14.8 ± 7.5 mEq/day in typical PHPT 6

Diagnostic Algorithm: PHPT vs FHH

Step 1: Calculate Calcium-to-Creatinine Clearance Ratio (CCCR)

CCCR is the preferred initial test to distinguish PHPT from FHH 2, 5, 4:

  • CCCR >0.02: Strongly suggests PHPT (proceed with standard PHPT evaluation) 5, 3

  • CCCR 0.01-0.02: Intermediate zone—obtain 24-hour urine calcium for additional data 5, 3

  • CCCR <0.01: Raises suspicion for FHH—proceed to Step 2 5, 7

Step 2: When CCCR <0.01, Use Clinical Context to Exclude FHH

A CCCR <0.01 occurred in 17% of PHPT patients, so do not reflexively order genetic testing 7. Instead, FHH can be excluded by:

  • 24-hour urine calcium >100 mg/day (>2.5 mmol/day): Rules out FHH with 95.2% negative predictive value 5, 7

  • Prior documented normocalcemia: FHH presents with lifelong hypercalcemia from infancy 7

  • Renal insufficiency (eGFR <60): Reduces calcium excretion independent of FHH 7

  • Absence of family history of hypercalcemia: FHH is autosomal dominant 7

  • Thiazide diuretic use: Lowers urinary calcium and can mimic FHH 7

Step 3: Genetic Testing for FHH

Order genetic testing (CASR, GNA11, AP2S1 genes) only when:

  • CCCR <0.01 AND 24-hour urine calcium <100 mg/day (<2.5 mmol/day) 5

  • Family history of hypercalcemia with failed parathyroid surgery 5

  • Young age at presentation with mild hypercalcemia 5

In practice, only 1-4% of patients with suspected PHPT require genetic testing when this algorithm is followed 7

Test Performance Characteristics

24-Hour Urine Calcium

  • Sensitivity for PHPT: 96% (using cut-off ≥2.5 mmol/24hr) 3

  • Specificity for FHH: 29.4% (using cut-off <2.5 mmol/24hr) 3

  • Negative predictive value for FHH: 95.2% when <2.5 mmol/24hr 5

CCCR

  • Specificity for FHH: 93% (using cut-off <0.02) 3

  • Sensitivity for PHPT: 47% (using cut-off >0.02) 3

  • At CCCR cut-off ≤0.015, negative predictive value for FHH is 100% 5

  • At CCCR cut-off ≤0.020, negative predictive value for FHH is 100% with positive predictive value of only 2.33% 5

Clinical Pitfalls to Avoid

  • Do not rely solely on 24-hour urine calcium to exclude FHH—it has poor specificity (29.4%) and will prompt unnecessary genetic testing in many PHPT patients 3

  • Do not order genetic testing when CCCR <0.01 without first checking 24-hour urine calcium and clinical context—this avoids unnecessary testing in 99% of cases 7

  • Always check vitamin D status before interpreting urinary calcium—deficiency suppresses calcium excretion and can make PHPT mimic FHH 2

  • Interpret CCCR in context of renal function—chronic kidney disease lowers urinary calcium independent of FHH 7

  • Use albumin-adjusted serum calcium when calculating CCCR, as 70.3% of UK clinicians do 4

  • Four-gland hyperplasia is more common when CCCR <0.01 (17% vs 4% when CCCR ≥0.01), but surgical outcomes remain equivalent 7

References

1
Guideline

Diagnostic Criteria for Hyperparathyroidism

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

2
Guideline

Diagnosing Primary Hyperparathyroidism

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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