Laboratory Workup for Muscle Cramps
Order creatine kinase (CK) first as the single most important test to differentiate benign muscle cramps from serious inflammatory myositis or rhabdomyolysis, followed by a basic electrolyte panel (sodium, potassium, calcium, magnesium) to identify common reversible metabolic causes. 1
Essential Initial Laboratory Tests
The core laboratory workup should include:
Creatine kinase (CK): This is the most critical test. Markedly elevated CK indicates myositis or rhabdomyolysis, while normal CK effectively rules out inflammatory muscle disease. 1 However, be aware that CK may be normal in the first 24-48 hours of acute muscle injury, so repeat testing may be necessary if clinical suspicion remains high. 1
Electrolyte panel (sodium, potassium, calcium, magnesium): Electrolyte abnormalities are common reversible causes that must be identified early. 1 These metabolic derangements are frequently encountered in clinical practice and can be easily corrected once identified. 2, 3
Renal function (creatinine, BUN): Kidney dysfunction causes electrolyte imbalances and uremic myopathy, making this assessment essential. 1
Inflammatory markers (ESR, CRP): Highly elevated inflammatory markers with normal CK suggest polymyalgia-like syndrome rather than true myositis, which is critical for treatment decisions. 1
Additional Testing When Weakness Accompanies Cramps
If the patient presents with muscle weakness in addition to cramps, expand the workup to include:
Complete blood count (CBC): To rule out systemic infection or hematologic disorders. 1
Comprehensive metabolic panel: Including liver enzymes (AST, ALT) as part of a thorough metabolic assessment. 1
Thyroid function tests (TSH, free T4): Thyroid disorders can cause muscle symptoms and are easily treatable once identified. 1
When Myositis is Suspected
If clinical presentation suggests inflammatory myopathy:
Aldolase: An additional muscle enzyme marker that complements CK. 1
Troponin: Myositis can involve cardiac muscle, which is life-threatening and requires immediate recognition. 1
Myositis-specific antibody panel: Consider this testing, though there is no evidence that specific autoantibodies predict immune checkpoint inhibitor-associated myositis. 1
Critical Pitfalls to Avoid
Do not assume normal CK rules out all serious pathology early in presentation: CK may be normal in the first 24-48 hours of acute muscle injury. 1 If clinical suspicion remains high, repeat testing is necessary.
Always ask about medications: Statins, corticosteroids, and other drugs cause myopathy and typically show normal or mildly elevated CK. 1, 2 This is a frequently overlooked cause of muscle symptoms.
Consider the broader differential: Muscle cramps may be symptomatic of radiculopathies, Parkinson's disease, hypothyroidism, diabetes mellitus, vascular problems, or metabolic myopathies. 2, 3 The laboratory workup should be guided by clinical context.
When to Proceed Beyond Laboratory Testing
If laboratory tests are unrevealing but symptoms persist:
Electromyography (EMG): Shows muscle fibrillations in myopathy but is normal in benign cramps. 1
MRI of affected muscles: Demonstrates edema and inflammation in myositis. 1
Muscle biopsy: Confirmatory test for inflammatory myopathy when diagnosis remains uncertain. 1
Special Considerations
In patients with cirrhosis and muscle cramps, the approach differs: diuretics should be discontinued if incapacitating muscle cramps develop, and albumin infusion or baclofen administration (10 mg/day, with weekly increases of 10 mg/day up to 30 mg/day) are recommended. 4
For polyneuropathy evaluation (which may present with cramps), screening should include complete blood count, erythrocyte sedimentation rate, comprehensive metabolic panel (blood glucose, renal function, liver function), thyroid function tests, serum B12 with metabolites (methylmalonic acid and homocysteine), and serum protein immunofixation electrophoresis. 4 Vitamin B12 deficiency was found in 2.2-8% of patients with polyneuropathy, and testing metabolites increases diagnostic yield when serum B12 is in the low normal range of 200-500 pg/dL. 4