Clinical interpretation of population-specific adjusted calcium values

To the Editor

My letter to Clinical Chemistry about adjusted calcium and ionised calcium ¹ has sparked a request for me to give my view on recent papers by Jassam et al.^2,3 about population-specific adjustment equations. To do so, I need to start nearly 50 years ago.

Our first 1973 adjusted calcium investigation ⁴ used 200 consecutive specimens with clinical requests for ‘liver function tests’ but not for calcium that were received from wards, outpatient departments and general practitioners, but excluded those from the department of renal medicine. They were measured on our new non-discretionary SMA Plus analyzer. We thought such specimens would have a high prevalence of abnormal proteins from patients with a low prevalence of clinically suspected disorders of calcium homeostasis. Calcium concentrations correlated closely with albumins from 20 to 48 g/L (r = 0.867). The least squares regression intercept value was close to reported values for ultrafilterable calcium and its width was similar to that of our calcium reference range.

Rather than report these low values as ‘non-protein-bound calcium’, we decided to adjust them by adding a constant, the difference between the intercept value and the mean of our normal (blood donor) reference range, 2.40 mmol/L, in an attempt to predict what an abnormal total calcium would be if its albumin were normal. The object was to help clinicians decide whether further investigation of calcium homeostasis was needed. The 95% confidence interval of the 200 patients’ adjusted calcium values was 2.25–2.60 mmol/L. We subsequently studied 100 consecutive sera received which did have requests for calcium (again excluding those from renal medicine). Only nine of 22 low calcium values remained low after adjustment and two that were high were joined by a third after adjustment, all with carcinoma of the breast. Jassam et al. ³ said they used the ‘Payne method’ to calculate adjustment equations for their populations.

I strongly endorse the views expressed by Gethin Roberts ⁵ in his letter about the calcium adjustment procedure used by Jassam et al.^2,3 I, too, do not understand why the authors chose to adjust data screened by ‘Payne criteria’ to the mean calcium concentration of the population rather than to the mean of the normal reference range that is used by clinicians.