What is the appropriate management for a 45-year-old woman with fatigue, muscle weakness, and cramping in the lower extremities, hypertension (HTN) treated with lisinopril (angiotensin-converting enzyme inhibitor), mildly decreased strength in the proximal muscles, sluggish ankle jerks, normal erythrocyte sedimentation rate (ESR), and elevated serum creatine kinase (CK) level?

Appropriate Management for a Patient with Muscle Weakness, Elevated CK, and Possible Medication-Induced Myopathy

The most appropriate next step in management for this 45-year-old woman with fatigue, muscle weakness, and elevated creatine kinase is to order serum TSH and free T4 tests (option B).

Clinical Presentation Analysis

The patient presents with several key findings that guide our diagnostic approach:

• 45-year-old woman with fatigue and muscle weakness in lower extremities
• Cramping in legs after walking short distances
• Hypertension treated with lisinopril (ACE inhibitor)
• Mildly decreased strength in proximal muscles of lower extremities
• Sluggish ankle jerks bilaterally
• Normal erythrocyte sedimentation rate (ESR)
• Elevated serum creatine kinase (CK) level

Diagnostic Reasoning

Medication-Induced Myopathy vs. Thyroid Dysfunction

The combination of proximal muscle weakness, elevated CK, and use of lisinopril creates a clinical picture that strongly suggests either:

1. Medication-induced myopathy: ACE inhibitors like lisinopril can cause muscle symptoms and elevated CK levels 1, 2. However, this is less common than with other medications like statins.

2. Thyroid dysfunction: Hypothyroidism is a common cause of proximal muscle weakness, fatigue, and elevated CK levels. This condition can present with exactly the constellation of symptoms seen in this patient.

Why TSH and Free T4 Testing is Most Appropriate

Thyroid function testing is the most appropriate next step because:

• Hypothyroidism is a common, treatable cause of proximal muscle weakness and elevated CK
• The pattern of proximal weakness with preserved reflexes (though sluggish) is classic for metabolic myopathies like hypothyroidism
• Normal ESR suggests against inflammatory myopathies
• Testing is non-invasive and highly diagnostic if positive

Evaluation of Other Options

A. Antinuclear antibody (ANA) test

• Less appropriate because the normal ESR makes inflammatory myopathies less likely
• The absence of other systemic symptoms (rash, arthritis, fever) makes autoimmune conditions less probable

C. Electromyogram (EMG)

• Would be a reasonable second step if thyroid testing is normal
• More invasive and should be reserved for when simpler tests don't yield a diagnosis
• EMG would help distinguish between myopathy, neuropathy, and neuromuscular junction disorders

D. Muscle biopsy

• Most invasive option and should be reserved for when less invasive testing is inconclusive
• Premature at this stage before ruling out common metabolic causes

Management Algorithm

1. First step: Order TSH and free T4 tests to evaluate for thyroid dysfunction

   • If abnormal: Treat thyroid disorder and reassess symptoms
   • If normal: Proceed to step 2

2. Second step: Consider medication effect

   • Evaluate timing of symptom onset in relation to lisinopril initiation
   • Consider trial of alternative antihypertensive if clinically appropriate

3. Third step: If steps 1-2 are negative, proceed with EMG to characterize the nature of the weakness

4. Fourth step: Based on EMG results, consider:

   • Additional laboratory testing (ANA, myositis-specific antibodies)
   • Muscle biopsy if a specific myopathy is suspected

Clinical Pearls

• Up to 10% of patients with hypothyroidism present with myopathy as their predominant symptom
• CK elevation can be seen in both hypothyroidism and medication-induced myopathies
• Proximal muscle weakness (difficulty climbing stairs, rising from chairs) is characteristic of myopathy rather than neuropathy
• While lisinopril is not commonly associated with myopathy, any medication should be considered as a potential cause of muscle symptoms 3

By starting with thyroid function testing, we follow a logical, stepwise approach from least to most invasive testing, prioritizing the most common and treatable causes of the patient's presentation.