Increased CK activity in serum without symptoms: Further investigations often unnecessary

Introduction: Increased activity of the enzyme creatine kinase (CK) in serum is not infrequently encountered in routine diagnostic laboratory investigations. Patients are often referred to a neurologist specialized in neuromuscular disorders for evaluation. In many cases, however, this hyperCKemie is physiological or results from physical activity or muscle trauma. Then, further investigations are not necessary. Case description: We report four cases of hyperCKemie, two of which are physiological or due to non-neuromuscular factors (medication, physical activity). In the other two patients, the hyperCKemia was the first recognized sign of an underlying neuromuscular disorder. In these two cases, specific aspects of the (family) history or physical examination prompted further investigations which led to the diagnosis of malignant hyperthermia and Becker muscular dystrophy respectively. We present guidelines for ancillary investigations by general practitioners or specialist who encounter patients with hyperCKemie. These include three steps: 1) Is the hyperCKemia persistent? (HyperCKemia is defined as a CK > 1.5 times the upper limit of normal of the local laboratory for the specific sex and race; it is verified in two measurements under standardized conditions); 2) Is there a non-neuromuscular cause for the hyperCKemia? (medications, local trauma, metabolic or endocrine causes); and 3) Which test to perform in case of persistent hyperCKemia without non-neuromuscular causes? (extended familiy history, electromyography to confirm a clinical suspicion of a neurogenic disorder, genetic testing for dystrofinopathy, muscle biopsy in other cases). Conclusion: We discuss the various physiological and other non-neuromuscular factors that may cause hyperCKemie. It is important to recognize these causes before referral to a neurologist with neuromuscular expertise. This can be done by any physician encountering patients with hyperCKemia.