Adjusting copper concentrations for caeruloplasmin levels in routine clinical practice

Background: An investigation on copper metabolism usually includes the measurement of serum levels of copper and caeruloplasmin. Using these levels, some laboratories derive levels of non-caerulo-plasmin-bound copper (NCC); however, a considerable number of patients may show negative values, which is not physiologically possible. Aim: To derive an equation for adjusted copper in a manner similar to that widely accepted for adjusted calcium. Methods: A linear regression equation for the relationship between caeruloplasmin and copper was used: [copper] (mu mol/l) = 0.0526x[caeruloplasmin] (mg/l). An equation for copper adjusted for caeruloplasmin was derived using this equation and the reference interval of 10-25 mmol/l for copper. Results: The derived equation was [adjusted copper] (mmol/l) = [total copper] (mmol/l)+0.052x[caeruloplasmin] (mg/l)+17.5(mmol/l). The adjusted copper concentrations on the 2.5th and 97.5th centiles were 12.7 and 21.5 mmol/l, respectively, with the population having a gaussian distribution. The relationship between NCC and the adjusted copper concentrations is linear and independent of caeruloplasmin concentration. Conclusion: Calculation of copper adjusted for caeruloplasmin uses the same variables as those for NCC. Accordingly, the problems that are caused by the lack of specificity of caeruloplasmin immunoassays are the same as those identified for NCC. This calculation, however, overcomes the negative values that are found in a considerable minority of patients with NCC, as well as age and sex differences in the caeruloplasmin reference interval. As the concept is already familiar to non-laboratory healthcare professionals in the form of calcium adjusted for albumin, this method is potentially less confusing than that for NCC.