IM Board Review

Progressive muscle weakness: More there than meets the eye

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Our patient, a 56-year-old woman, presents with proximal muscle weakness in all four limbs. It started a few months ago and has gradually become severe, so that she now has difficulty rising from a seated position and has trouble opening jars. She has fallen several times. She says she has no muscle pain, difficulty swallowing, or difficulty breathing.

She sought medical attention at another hospital and was found to be hypothyroid, with a thyrotropin (thyroid-stimulating hormone [TSH]) level of 38 μU/mL (reference range 0.4–5.5), for which she was started on levothyroxine (Synthroid) 100 μg daily. She also had a low serum potassium level, for which potassium supplements and spironolactone (Aldactone) were started. She was taking furosemide (Lasix) 20 mg/day at the time.

Despite the thyroid replacement therapy, she continued to become weaker and had more falls. She also noticed a new, nonpainful rash on her lower abdomen.

Review of systems

  • Night sweats
  • Leg swelling
  • Puffiness and discoloration around the eyes, with easy bruisability.

Medical history

  • Diabetes mellitus
  • Seizures in the 1970s
  • Resection of a thymic tumor in 2003 (the exact pathology is unknown)
  • Cirrhosis of unknown etiology
  • No known history of hypertension
  • No history of alcohol or intravenous drug use
  • Quit smoking many years ago
  • Coronary artery bypass surgery in 2003
  • One sibling with myasthenia gravis.

Medications

  • Levothyroxine
  • Rosuvastatin (Crestor)
  • Omeprazole (Prilosec)
  • Spironolactone
  • Furosemide
  • Potassium chloride
  • Metoprolol tartrate (Lopressor)
  • Metformin (Glucophage)
  • Ramipril (Altace).

Physical examination

She is hemodynamically stable and is not hypertensive. Her thyroid is not enlarged. Her lungs are clear to auscultation. Her heart sounds are normal, except for a nonradiating pansystolic murmur most audible at the apex.

Her abdomen is soft and is not distended. Her abdominal rash has a dermatomal distribution consistent with an L1 distribution, with vesicles over an erythematous base. Purpuric lesions are noted over her lower extremities.

Her leg strength is 3 on a scale of 5 on both sides; her arm strength is normal. Ankle and knee reflexes are absent bilaterally.

Initial laboratory analysis

Initial laboratory analysis (Table 1) indicates mild renal insufficiency, hypokalemia, elevated liver enzymes, and a normal TSH level. An acetylcholine receptor antibody assay is negative. Her creatine kinase level is also normal.

PROGRESSIVE MUSCLE WEAKNESS

1. What are possible causes of her muscle weakness?

  • Myasthenia gravis
  • Hypothyroidism
  • Dermatomyositis-polymyositis
  • Drug-induced myopathy
  • Cushing syndrome
  • All of the above

All of these are potential causes of muscle weakness.

Myasthenia gravis

Myasthenia gravis, an autoimmune disease, can affect people of all ages and either sex. It presents with muscle weakness and fatigability, which characteristically fluctuate during the day. Some patients present in crisis with respiratory failure, which may require ventilatory support.1,2

Myasthenia gravis is characterized by auto-antibodies against the postsynaptic membrane of the neuromuscular junction. Most patients have antibodies to the extracellular portion of the acetylcholine receptor; a small number of patients have antibodies against a muscle-specific tyrosine kinase that interacts with this receptor.

About 15% of patients with myasthenia gravis have a thymoma thought to be involved in the pathogenesis of the disease. Treatments include immune suppressive therapy and thymectomy.

Our patient has a history of thymic lesion resection, but her antibody workup for myasthenia gravis was negative.

Hypothyroidism

Hypothyroidism, the most common disorder of the thyroid gland, is especially prevalent in women.3 Its common symptoms include fatigue, exercise intolerance, muscle weakness, cramps, and stiffness.

Both the TSH and the free thyroxine (T4) level must be measured to diagnose hypothyroidism. This information can also help differentiate primary hypothyroidism (ie, due to a defect in the thyroid gland) from secondary hypothyroidism (ie, due to a defect in the pituitary gland). Elevated TSH with low free T4 levels indicates primary thyroid failure, whereas the combination of a normal or low TSH and a low free T4 usually indicates pituitary failure. Subclinical hypothyroidism is characterized by mildly to moderately elevated TSH, but total T4 and free T4 values are still within the reference range. Replacement therapy is with levothyroxine.3–6

Our patient has a history of hypothyroidism, which could explain her muscle weakness, but she is currently on replacement therapy, and her TSH level on admission was normal.

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