Lab Interpretation: High skeletal muscle creatine kinase in adults

ALGORITHM — 

(algorithm 1)

IMMEDIATE ACTION — 

Rapidly identify patients with a potentially life-threatening muscle injury (rhabdomyolysis) usually associated with extreme (sometimes over 1000-fold) creatine kinase (CK) skeletal muscle enzyme elevations, electrolyte imbalances, and acute kidney injury (AKI), as may occur in the following settings:

●Muscle trauma, compression, vascular and cardiac surgeries

●Drugs/toxins

●Sepsis

●Heat stroke

Provide hemodynamic support. Identify any triggering event or drug/toxin (eg, dopamine antagonists, serotonin agonists, cocaine, amphetamine, alcoholic binge) (table 1). Manage fluid and electrolyte abnormalities. Life-saving interventions for critically ill patients should not be delayed while awaiting the results of diagnostic testing. (See "Rhabdomyolysis: Clinical manifestations and diagnosis" and "Rhabdomyolysis: Epidemiology and etiology".)

Obtain serial:

●CK measurements

●Serum electrolytes, creatinine, glucose

In patients whose CK does not decline as expected (ie, within three to five days of cessation of muscle injury), continued muscle injury or the development of a compartment syndrome may be present. (See "Acute compartment syndrome of the extremities".)

INITIAL EVALUATION — 

Patients not requiring immediate action require a timely evaluation to determine the clinical significance of the creatine kinase (CK) level. CK elevation may be incidentally noted on a routine biochemistry panel, it may be part of a diagnostic evaluation for muscle weakness to identify myopathy or motor neuron disease, or it may be used to monitor the course of patients with known muscle disease (eg, rhabdomyolysis, dermatomyositis, polymyositis).

Incidentally noted — When an elevated CK is noted on a routine biochemical panel in a patient with minimal or no muscle symptoms and no muscle weakness, neuromuscular disease is unlikely. However, an asymptomatic or minimally symptomatic CK elevation could be an early or only manifestation of neuromuscular disease.

In the absence of neuromuscular disease, muscle enzymes may be elevated in the following settings:

●Postexercise

●Iatrogenic muscle injury (eg, intramuscular injection, major surgery, electromyography, muscle biopsy)

●Renal disease

Confirm no recent intramuscular injections and obtain repeat CK after the patient has refrained from intense exercise for at least three to seven days.

Repeat CK normal or declining — No further evaluation of elevated CK.

Persistent CK elevation ≤1.5 times upper limit of normal and stable — If the CK level remains ≤1.5 times the upper limit of normal (based on age, sex, and race) and there are no worrisome clinical findings, no further evaluation for elevated CK is required. Because the normal range of CK in reference labs is two standard deviations above and below the mean of control samples, 5 percent of healthy individuals will have values greater than the normal range.

However, patients who develop worrisome clinical findings (eg, weakness, atrophy) or have an abnormal developmental history or suggestive family history of neuromuscular disorders should be evaluated for muscular dystrophies (eg, Becker, myotonic dystrophy), motor neuron disease (eg, ALS), and myopathies, disorders in which the CK may be mildly elevated (or normal). Obtain specialty consultation if indicated. (See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis" and "Diagnosis of amyotrophic lateral sclerosis and other forms of motor neuron disease", section on 'Laboratory testing'.)

Persistent CK elevation >1.5 times upper limit of normal or rising

●Perform a careful clinical examination to confirm absence of muscle weakness or myalgias. (See 'Muscle weakness or myalgias present' below.)

●Review the medication list and inquire about recent herbal remedies or drug exposures that could lead to a drug-induced CK elevation, particularly if the patient is treated with a statin drug. In mild cases of drug-induced CK elevation, patients may be incidentally found to have elevated CK levels with no associated muscle symptoms. (See "Drug-induced myopathies" and "Statin muscle-related adverse events".)

●Consider the possibility of macro CK, particularly if there is an unexpected increase in the MB isoenzyme, which can be identified by CK electrophoresis.

●Electromyography (EMG) can be performed to investigate nerve or muscle etiologies that might contribute to CK elevation.

●If worrisome clinical features (eg, weakness, muscle atrophy) develop or there is a family history of neuromuscular disorder, obtain specialty consultation. Neuromuscular disease specialists may obtain genetic studies, such as next generation sequencing neuromuscular panel tests, to identify a molecular diagnosis. (See 'Muscle weakness or myalgias present' below.)

Muscle weakness or myalgias present — True muscle weakness with a serum CK >1000 units/L usually indicates muscle disease. The major categories of muscle disease include inflammatory disorders, endocrinopathies, metabolic myopathies, drugs and toxins, infections, and the various causes of rhabdomyolysis (table 2). Muscle weakness accompanied by more modest elevation of CK may occur in some primary neurologic disorders, particularly motor neuron disease (eg, amyotrophic lateral sclerosis [ALS]).

Review the medication list and any recent drug exposures. Drugs may cause elevations in CK ranging from mild to massive. The clinical manifestations of a drug-induced myopathy are variable and include myalgia, fatigue, muscle weakness, or myoglobinuria.

Obtain:

●Serum electrolytes, creatinine, calcium, magnesium, phosphate, glucose

●Liver biochemical tests

●Thyroid-stimulating hormone (TSH)

●EMG

If an inflammatory myopathy and/or systemic rheumatic disease is suspected, obtain rheumatologic consultation.

If motor neuron disease (eg, ALS, spinal muscle atrophies) is suspected, obtain neurologic consultation. Neuromuscular disease specialists may obtain genetic studies (eg, next generation sequencing neuromuscular panel tests) to identify a molecular diagnosis. Testing should be a joint decision with the ordering provider and the patient. Access to a genetic counselor and geneticist should be available.

Monitoring of disease course — CK is used to monitor the course of patients with known rhabdomyolysis, dermatomyositis, and polymyositis. The frequency of monitoring depends on the clinical setting and whether symptoms are improving with therapy or whether an exacerbation is suspected.

REFERENCE RANGE — 

Normal creatine kinase (CK) levels vary depending on the patient population, muscle mass, and clinical laboratory. CK levels are higher in Black Americans compared with White, Hispanic, or Asian Americans and higher in males than females. Interpretation of a specific abnormal test result should be based upon the reference range reported with that result.

CITATIONS — 

The supporting references for this content are accessible in the linked topics.