Effect of newly proposed CK reference limits on neuromuscular diagnosis.

The objective was to determine the effect of a proposed increase in the upper reference limits of serum creatine kinase (CK) on neuromuscular disease diagnosis. This was a retrospective study of 94 Caucasian subjects (49 women and 45 men) in whom a neuromuscular physician ordered a CK as part of their evaluation. The patients were divided into two groups: those with diagnoses that either should or could elevate serum CK, and those with diagnoses that should not elevate serum CK. Sensitivities and specificities of the manufacturer's and the newly proposed upper reference limits were determined. For women, raising the upper reference limit of CK from 140 IU/L to 201 IU/L reduced the sensitivity of the test from 50% to 29%, while increasing the specificity from 67% to 80%. For men, raising the upper reference limit of CK from 174 IU/L to 322 IU/L reduced the sensitivity from 80% to 60%, while increasing the specificity from 63% to 80%. The newly proposed upper reference limits resulted in a false-negative CK of clinical significance in 7 of 94 subjects. Increasing the upper reference limit for CK reduced the sensitivity and increased the specificity of serum CK for neuromuscular disease diagnosis. Such a change will reduce unnecessary referrals and invasive diagnostic testing in patients with asymptomatic CK elevations. The clinical impact of the loss in sensitivity is small. If these new upper reference limits are adopted, neuromuscular physicians should be aware that a normal CK level does not exclude a diagnosis of myopathy.