Adjusting copper concentrations for caeruloplasmin levels in routine clinical practice

Area of Science:

• Clinical Chemistry
• Trace Element Metabolism
• Biochemical Assays

Background:

• Copper metabolism assessment typically involves serum copper and caeruloplasmin measurements.
• Existing methods for calculating non-caeruloplasmin-bound copper (NCC) can yield physiologically impossible negative values.
• Caeruloplasmin immunoassays may lack specificity, impacting copper level accuracy.

Purpose of the Study:

• To develop an equation for adjusted copper, analogous to adjusted calcium calculations.
• To provide a more accurate and interpretable measure of copper status in patients.

Main Methods:

• A linear regression model established the relationship between copper and caeruloplasmin: [copper] (micromol/l) = 0.052x[caeruloplasmin] (mg/l).
• An equation for copper adjusted for caeruloplasmin was derived using this regression and the copper reference interval (10-25 micromol/l).
• The derived equation is: [adjusted copper] (micromol/l) = [total copper] (micromol/l) + 0.052x[caeruloplasmin] (mg/l) + 17.5 (micromol/l).

Main Results:

• The adjusted copper equation produced physiologically plausible values, with 2.5th and 97.5th centiles at 12.7 and 21.5 micromol/l.
• The distribution of adjusted copper concentrations was Gaussian.
• The relationship between non-caeruloplasmin-bound copper (NCC) and adjusted copper was linear and independent of caeruloplasmin levels.

Conclusions:

• The adjusted copper calculation addresses the limitations of NCC, including negative values and age/sex variations in caeruloplasmin reference intervals.
• This method is potentially less confusing for clinicians than NCC due to its similarity to adjusted calcium calculations.
• It offers a more reliable assessment of copper status, mitigating issues from caeruloplasmin immunoassay specificity.