The copper/caeruloplasmin ratio in routine clinical practice in different laboratories

Background: The diagnosis of copper deficiency and excess states is challenging. It was hoped that the non-caeruloplasmin-bound ("free'') copper would reduce this difficulty; however, it has its own problems. The copper/caeruloplasmin ratio has been advocated as an alternative index of copper status, especially as it would not need gender-derived or age-derived reference intervals. However, there are no comparative data for different populations using different assays. Method: Independent paired copper and caeruloplasmin data were retrospectively obtained for three laboratories. From these data, the copper/caeruloplasmin ratio was calculated, and descriptive statistics for the populations and methods were obtained. The relationship between the copper/caeruloplasmin ratio and both copper and caeruloplasmin were also investigated for the three laboratories. Results: All three datasets displayed a non-Gaussian distribution. The Burton median was statistically different from the two other medians, which did not differ significantly from each other. The regression lines for both copper and caeruloplasmin with the ratio differed from each other. Conclusion: The copper/caeruloplasmin ratio behaves differently depending on the laboratory, the population studied, or both. Thus, cut-offs in the literature are not transferable. Each laboratory should therefore derive its own cut-offs.