What laboratory tests do you order to evaluate a patient with weakness?

Laboratory Workup for Weakness

For a patient presenting with weakness, order a comprehensive metabolic panel, complete blood count with differential, thyroid-stimulating hormone (TSH), creatine kinase (CK), and inflammatory markers (ESR/CRP) as your initial laboratory evaluation.

Core Laboratory Panel

The essential first-tier laboratory tests for evaluating weakness include:

• Complete Blood Count (CBC) with differential – identifies anemia, infection, or hematologic disorders that commonly contribute to weakness 1
• Complete Metabolic Panel – includes electrolytes (sodium, potassium, calcium, magnesium, phosphate), renal function (BUN, creatinine), hepatic function (AST, ALT, alkaline phosphatase), and glucose 1
• Thyroid-Stimulating Hormone (TSH) – screens for hypo- or hyperthyroidism, both common reversible causes of weakness 1
• Creatine Kinase (CK) and Aldolase – essential for detecting muscle inflammation or myositis; transaminases (AST/ALT) and LDH may also be elevated in muscle disease 1
• Inflammatory markers (ESR and CRP) – help identify inflammatory or autoimmune conditions contributing to weakness 1

Additional Testing Based on Clinical Context

If Muscle Disease is Suspected

When the history and examination suggest primary muscle pathology (true motor weakness rather than fatigue, possible myositis or myopathy):

• Troponin – evaluate for myocardial involvement, particularly if CK is elevated 1
• Vitamin B12 level – deficiency can cause weakness and neuropathy 1
• Homocysteine level – elevated in B12 deficiency and other metabolic conditions 1
• Urinalysis – screen for rhabdomyolysis if CK is markedly elevated 1
• Autoantibody testing – consider anti-AChR and antistriational antibodies if myasthenia gravis is suspected; myositis-specific antibodies (anti-TIF1γ, anti-NXP2) if inflammatory myopathy is considered 1

If Cognitive or Behavioral Symptoms Coexist

When weakness presents alongside cognitive changes or in elderly patients:

• Glycohemoglobin (HbA1c) – assess for diabetes and glycemic control 1
• Lipid profile – part of comprehensive cardiovascular risk assessment 1
• Urinalysis – screens for systemic disease 1

Critical Interpretation Points

Distinguishing True Weakness from Fatigue

The most challenging initial task is determining whether the patient has true muscle weakness (loss of power with reduced motor function) versus subjective fatigue 2, 3. This distinction fundamentally changes your diagnostic approach and laboratory interpretation.

• True weakness shows objective loss of motor strength on formal testing (use Medical Research Council Manual Muscle Testing scale) 3
• Fatigue presents as generalized tiredness without demonstrable motor strength loss 2, 4

Pattern Recognition Guides Testing

• Asymmetric weakness suggests neurologic conditions (stroke, radiculopathy, neuropathy) – prioritize imaging over extensive metabolic workup 3
• Symmetric weakness with elevated CK (≥3× upper limit of normal) indicates myositis or myopathy – add troponin, autoantibodies, and consider urgent rheumatology/neurology referral 1
• Weakness with pain more commonly represents neuropathy or radiculopathy rather than primary muscle disease 3

Common Pitfalls to Avoid

Do not order muscle enzymes (CK, aldolase) in isolation without checking TSH and electrolytes – thyroid disorders and electrolyte abnormalities are more common reversible causes of weakness than primary muscle disease 1.

Recognize that normal CK does not exclude myopathy – some inflammatory myopathies and metabolic myopathies can present with normal or minimally elevated CK 1.

Check medication history before extensive workup – statins, corticosteroids, and other medications commonly cause weakness and may elevate CK 1, 3.

In patients over 60 years, consider frailty and sarcopenia as clinical syndromes that may present as generalized weakness without specific laboratory abnormalities 3.