A 45-year-old previously healthy man comes to the office due to worsening muscle pain and weakness over the past 6 months. Carrying heavy items such as groceries has become increasingly difficult, and any prolonged activity causes diffuse muscle cramps. He has also had a 4.5-kg (10-lb) weight gain over this time. The patient takes no medications and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 140/90 mm Hg and pulse is 56/min. BMI is 26 kg/m². Physical examination shows muscle weakness, predominantly of the shoulder and hip girdles. When the knee reflex is elicited, the quadriceps muscle contracts briskly but relaxation takes longer than normal. There are splitting and peeling of the nails. Serum creatine kinase is elevated. Which of the following tests is most likely to identify the cause of this patient's muscle weakness?

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11ec160b_3ac1_991b_9249_07d420574fed_MD0001_00 An elevated creatine kinase (CK) level suggests a myopathic process with myocyte damage and release of muscle enzymes into the circulation. Common causes of myopathy with elevated CK include hypothyroidism, muscular dystrophies, inflammatory muscle diseases, and medications such as HMG-CoA reductase inhibitors. This patient's fatigue, weight gain, bradycardia, and brittle nails are highly suggestive of hypothyroid myopathy. Decreased thyroid hormone levels impair muscle glycogen and triglyceride use and increase oxidative stress, resulting in myocyte injury. Patients typically presents with myalgias, proximal muscle weakness, decreased exercise tolerance, and cramping. Myoedema (focal muscle contraction at the site of percussion) and delayed relaxation of deep tendon reflexes are characteristic findings that are caused by impaired reuptake of calcium by the sarcoplasmic reticulum. Hypothyroid myopathy and elevations in CK can be the first signs of hypothyroidism and can precede other manifestations by months to years. The diagnosis can be confirmed with an elevated TSH level. (Choice A) A 24-hour urine cortisol test is used as an initial test for Cushing syndrome. This disorder can present with proximal muscle weakness and atrophy due to the direct catabolic effects of cortisol on skeletal muscle. However, there is no associated muscle pain or rise in CK, reflexes are normal, and other cushingoid features (eg, stria, dorsocervical fatty hypertrophy) are usually present. (Choices B and C) Myasthenia gravis is caused by autoantibodies against nicotinic acetylcholine receptors on the postsynaptic membrane of the neuromuscular junction. It presents with fluctuating weakness that worsens through the day. Lambert-Eaton syndrome is a paraneoplastic disorder associated with small cell carcinoma of the lung (which can be identified on CT scan). It is caused by autoantibodies against voltage-gated calcium channels on the presynaptic membrane, which cause decreased release of acetylcholine. These disorders affect the neuromuscular junction rather than the muscle itself, and CK is normal. (Choice D) Muscle biopsy is often needed for diagnosis of inflammatory myositis (eg, polymyositis, dermatomyositis). However, this patient has symptoms suggestive of hypothyroidism (eg, weight gain, bradycardia, brittle nails), and histologic findings in hypothyroid myopathy are often nonspecific. Educational objective: Hypothyroid myopathy presents with myalgias, proximal muscle weakness, elevated creatine kinase levels, and delayed relaxation of deep tendon reflexes. The diagnosis can be confirmed with an elevated TSH level. Other common causes of myopathy with elevated creatine kinase levels include inflammatory myopathies, muscular dystrophies, and HMG-CoA reductase inhibitors.

A 45-Year-Old Previously Healthy Man Comes to the Office Due