A 79-year-old man comes to the physician for follow-up 6 months after hospitalization for acute decompensated heart failure. He reports mild fatigue, weakness, and frequent muscle cramps but no shortness of breath. The patient has non-ischemic cardiomyopathy with a left ventricular ejection fraction of 40%. His medications include carvedilol (25 mg twice daily), lisinopril (20 mg daily) and furosemide (80 mg daily). He also takes daily lansoprazole for non-ulcer dyspepsia. Blood pressure is 122/80 mm Hg and pulse is 78/min. Jugular venous pressure is estimated at 5 cm H₂O. The lungs are clear to auscultation bilaterally. Peripheral pulses are 2+ bilaterally with trace peripheral edema. Neuromuscular examination shows 5/5 muscle strength in both upper and lower extremities, mildly increased reflexes, and no muscle tenderness. Laboratory results are as follows: Which of the following is the best next step in evaluation of this patient's symptoms?

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This patient's presentation suggests magnesium deficiency, likely due to combined proton pump inhibitor (PPI) and diuretic use. Hypomagnesemia is commonly due to either gastrointestinal (eg, diarrhea, malabsorption) or renal (eg, diuretics, alcohol) losses. Chronic use of PPIs can contribute to hypomagnesemia by disrupting the ability of intestinal epithelial cells to absorb magnesium. The risk is significantly higher when PPIs are combined with other drugs (eg, diuretics) associated with hypomagnesemia. Patients typically develop fatigue, weakness, neuromuscular hyperexcitability (eg, muscle cramps, tremor, hyperreflexia), and cardiovascular abnormalities (eg, QRS widening). Hypocalcemia, hypokalemia, and metabolic alkalosis are frequent biochemical findings associated with hypomagnesemia. Serum magnesium levels should be checked before starting long-term PPI therapy and periodically while on therapy, especially in patients who are concurrently taking diuretics. Hypomagnesemia usually improves with oral magnesium supplementation or with stopping the PPI. (Choice A) Arterial Doppler study is used for evaluation of peripheral vascular disease, which typically presents with claudication or intermittent leg pain. Examination can show diminished pulses, cool extremities, and skin ulcers, but hyperreflexia would not be seen. (Choice C) Serum parathyroid hormone (PTH) level is useful in evaluation of calcium disorders. Severe hypomagnesemia can often lead to hypocalcemia by inducing PTH deficiency and/or resistance, but this patient has a normal calcium level. (Choice D) Elevated creatine kinase would indicate a myositis, which can present with proximal muscle weakness and myalgias. Deep-tendon reflexes are typically decreased rather than increased with myositis. (Choice E) Iron deficiency can be associated with restless leg syndrome (RLS). RLS causes discomfort in the legs that is worse at rest and relieved with movement, in addition to periodic limb movements during sleep. However, RLS does not cause muscle cramps or hyperreflexia. Educational objective: Chronic proton pump inhibitor (PPI) use can impair intestinal magnesium absorption and cause hypomagnesemia. The incidence of hypomagnesemia is significantly higher when PPIs are combined with other drugs (eg, diuretics) associated with hypomagnesemia. __________ References: Systematic review: hypomagnesaemia induced by proton pump inhibition. (http://www.ncbi.nlm.nih.gov/pubmed/22762246) Proton-pump inhibitor use is associated with low serum magnesium concentrations. (http://www.ncbi.nlm.nih.gov/pubmed/23325090)

A 79-Year-Old Man Comes to the Physician for Follow-Up 6