Reference interval for albumin-adjusted calcium based on a large UK population.

Area of Science:

• Clinical Biochemistry
• Endocrinology
• Population Health

Background:

• Primary hyperparathyroidism is a common cause of hypercalcaemia, particularly in older women.
• Accurate reference intervals for albumin-adjusted serum calcium are critical for diagnosis.
• The current UK reference interval is based on consensus rather than empirical data.

Purpose of the Study:

• To establish a robust, data-driven reference interval for albumin-adjusted serum calcium in adult men and women.
• To provide updated upper limits for serum calcium that can aid in identifying hypercalcaemic disorders.

Main Methods:

• A cross-sectional study utilizing UK Biobank data from 502,524 men and women aged 40-69.
• Statistical outlier identification and exclusion were performed before calculating a 99% reference interval.
• Serum calcium, albumin, 25-hydroxyvitamin D, and estimated glomerular filtration rate (eGFR) were measured.

Main Results:

• A 99% reference interval for albumin-adjusted serum calcium was determined to be 2.19 to 2.56 mmol/L (8.76 to 10.24 mg/dL) after excluding outliers.
• Specific upper limits were identified: 2.59 mmol/L for older women, 2.57 mmol/L for younger women, and 2.55 mmol/L for men.
• The upper limit for older women effectively identifies high outliers (≥2.60 mmol/L).

Conclusions:

• The established reference intervals, particularly the upper limits, provide a more accurate basis for clinical assessment than the current consensus-based range.
• Updated reference intervals are recommended to improve the identification of hypercalcaemic disorders, such as primary hyperparathyroidism.
• These findings support the revision of current UK laboratory guidelines for serum calcium measurement.