A 72-year-old man presents to his primary care physician with weakness. He has felt very weak every morning with his symptoms persisting throughout the day. He notes minor improvement when he rides his bike but otherwise has not noticed any change in his symptoms with rest or ibuprofen use. The patient has lost 12 pounds recently and has had a chronic cough. The patient lives alone and drinks 7 alcoholic beverages per day and smokes 1-2 packs of cigarettes per day for the past 40 years. His temperature is 99.5°F (37.5°C), blood pressure is 177/108 mmHg, pulse is 93/min, respirations are 17/min, and oxygen saturation is 92% on room air. A chest radiograph is ordered as seen in Figure A. Which of the following diagnostic tests would most likely elucidate the cause of this patient's weakness?
CT scan of the chest
Electromyography
Lung biopsy
Muscle biopsy
Electromyography
This patient who presents with weakness that improves with activity in the setting of a lung mass most likely has Lambert-Eaton syndrome. The most appropriate diagnostic test to confirm this syndrome is electromyography.

Small cell lung cancer presents with fatigue, weight loss, cough, and a coin lesion on chest radiograph typically in a smoker. A common paraneoplastic syndrome in small cell lung cancer is Lambert-Eaton syndrome which presents with muscle weakness that improves with activity and worsens with rest. Activity improves symptoms due to accumulation of calcium with exercise which allows for acetylcholine release. This occurs secondary to antibodies against presynaptic calcium channels which decrease acetylcholine release. The diagnosis of Lambert Eaton syndrome can be confirmed with electromyography. Treatment includes addressing the underlying lung tumor.

Kesner et al. review the diagnosis and etiology of Lambert-Eaton syndrome. They discuss how this disease is associated with lung cancer. They recommend making the diagnosis using electrophysiologic studies.

Figure/Illustration A is a chest radiograph with a coin lesion in the left lung field (red circle). This finding is suggestive of small cell lung cancer.

Incorrect Answers:
Answer A: Blood laboratory tests could assess for multidrug resistance 1 protein (MDR-1 aka P-glycoprotein or ABCB1) which predicts resistance to chemotherapy for small cell lung cancer; however, it would not further elucidate this patient's muscle weakness.

Answers 2 & 4: CT scan of the chest and lung biopsy would further elucidate this patient's small cell lung cancer; however, it would not explain his weakness that improves with activity. In the setting of an elderly smoker with fatigue and weight loss and a coin lesion, the diagnosis of lung cancer is essentially established.

Answer E: Muscle biopsy would be the most accurate diagnostic test for dermatomyositis, polymyositis, and inclusion body myositis; however, it would not assess for conditions such as myasthenia gravis and Lambert-Eaton syndrome.

Bullet Summary:
Electromyography is the diagnostic test of choice for Lambert-Eaton syndrome.