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

Context: Primary hyperparathyroidism is a common condition and results in hypercalcaemia, especially in older women. Thus, it is critical to obtain a robust estimate for the upper limit of the reference interval for albumin‐adjusted serum calcium in the general population. The current reference interval in use in the UK (Pathology Harmony range, 2.20 to 2.60 mmol/L) was based on a consensus.

Objectives: To establish a reference interval for albumin‐adjusted serum calcium in men and women.

Design: Cross‐sectional study of men and women who did not have chronic kidney disease or vitamin D deficiency; outliers were identified statistically and then rejected and then a 99% reference interval was calculated.

Patients: 502 524 men and women aged 40 to 69 years from the UK Biobank Study.

Measurements: Serum total calcium, albumin, 25‐hydroxyvitamin D, estimated glomerular function (eGFR).

Results: We developed an equation for albumin‐adjusted serum calcium and applied it to 178 377 men and women who did not have chronic kidney disease or vitamin D deficiency. We identified 2962 (1.7%) as outliers, and when excluded, we report a 99% reference interval of 2.19 to 2.56 mmol/L (8.76 to 10.24 mg/dL). We found that for older (55‐69 years) and younger women (40‐55 years) the upper limits were 2.59 mmol/L and 2.57 mmol/L and that for all men, the upper limit was 2.55 mmol/L.

Conclusions: We have established an upper limit of the reference range for older women that would identify all high outliers (2.60 mmol/L and above). The upper limit for young women and for men is lower, at 2.57 and 2.55 mmol/L respectively. The current reference interval in use has to be updated and improved based on these findings. These upper limits may prove helpful for identifying hypercalcaemic disorders like primary hyperparathyroidism in clinical practice.