A 65-year-old woman comes to the office for follow-up. Two months ago, the patient was found to have low bone mineral density on screening dual-energy x-ray absorptiometry. Her serum calcium and vitamin D levels were within normal limits, and weekly alendronate therapy was prescribed. After starting the bisphosphonate, the patient had burning epigastric discomfort and nausea, which improved with over-the-counter antacids. She also has hypertension, for which she takes chlorthalidone. She takes no other medications or supplements and does not use tobacco, alcohol, or illicit drugs. The patient consumes a balanced diet and performs weight-bearing exercises regularly. Blood pressure is 110/66 mm Hg and pulse is 88/min. Physical examination is normal. Laboratory results are as follows: Serum creatinine was 0.8 mg/dL 2 months ago. Which of the following is the most likely cause of this patient's hypercalcemia?

Question

A 65-year-old woman comes to the office for follow-up.  Two months ago, the patient was found to have low bone mineral density on screening dual-energy x-ray absorptiometry.  Her serum calcium and vitamin D levels were within normal limits, and weekly alendronate therapy was prescribed.  After starting the bisphosphonate, the patient had burning epigastric discomfort and nausea, which improved with over-the-counter antacids.  She also has hypertension, for which she takes chlorthalidone.  She takes no other medications or supplements and does not use tobacco, alcohol, or illicit drugs.  The patient consumes a balanced diet and performs weight-bearing exercises regularly.  Blood pressure is 110/66 mm Hg and pulse is 88/min.  Physical examination is normal.  Laboratory results are as follows:  Serum creatinine was 0.8 mg/dL 2 months ago.  Which of the following is the most likely cause of this patient's hypercalcemia?

Quizplus · Accepted Answer

11ec25c8_d3ca_e91f_bc81_31c76c7f1418_MD0003_00 This patient has acute kidney injury associated with hypercalcemia and metabolic alkalosis (ie, increased serum bicarbonate). In light of her recent use of over-the-counter antacids, this most likely represents milk-alkali syndrome. Milk-alkali syndrome is due to excessive intake of calcium and absorbable alkali, usually in the form of calcium carbonate taken for heartburn (eg, antacids) or osteoporosis. Hypercalcemia in milk-alkali syndrome causes renal vasoconstriction and decreased glomerular blood flow. In addition, inhibition of the Na-K-2Cl cotransporter (due to activation of calcium-sensing receptors in the thick ascending loop) and impaired activity of antidiuretic hormone lead to the loss of sodium and free water. This results in hypovolemia and increased reabsorption of bicarbonate (augmented by the increased intake of alkali). Risk factors include chronic kidney disease and concurrent use of thiazide diuretics (which promote volume depletion and calcium retention), ACE inhibitors, or nonsteroidal anti-inflammatory drugs (which decrease glomerular filtration). Evaluation of milk-alkali syndrome should include measurement of serum parathyroid hormone (PTH), which would be expected to be suppressed. Additional findings can include hypophosphatemia due to intestinal binding of phosphate by calcium carbonate, and hypomagnesemia due to decreased renal reabsorption of magnesium. Initial management includes isotonic saline followed by loop diuretics (eg, furosemide). (Choice A) Bisphosphonate-induced osteonecrosis is rare in patients on low-dose bisphosphonates for osteoporosis and is typically associated with local pain (eg, in the mandible) and exposed bone. Bisphosphonates generally cause hypocalcemia, not hypercalcemia. (Choices C and D) Primary hyperparathyroidism can cause hypercalcemia and increased renal production of 1,25-dihydroxyvitamin D. However, it does not cause alkalosis, and when renal insufficiency occurs, it is usually associated with more severe hypercalcemia. (Choice E) Overdiuresis with thiazide diuretics (eg, chlorthalidone) can cause hypercalcemia, hypomagnesemia, and a contraction alkalosis with renal insufficiency. However, this is usually associated with hypokalemia, and not hypophosphatemia. Educational objective: Milk-alkali syndrome is characterized by hypercalcemia, acute kidney injury, and metabolic alkalosis. It is caused by excessive intake of calcium and absorbable alkali, usually in the form of calcium carbonate taken for heartburn or osteoporosis. References: Calcium-alkali syndrome in the modern era. (http://www.ncbi.nlm.nih.gov/pubmed/24288027)

A 65-Year-Old Woman Comes to the Office for Follow-Up