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Hypercalcemia in malignancy: This patient's presentation of altered mental status with severe dehydration, vomiting, and abdominal pain in the setting of malignancy suggests paraneoplastic syndrome of hypercalcemia. Electrolyte tests confirmed the diagnosis, revealing the following levels: Ca, 14.8 mg/dL; K, 5.8 mmol/L; BUN, 90 mg/dL; and creatinine, 2.4 mg/dL. Hypercalcemia is relatively common. More than 90% of cases are associated with hyperparathyroidism leading to increased Ca absorption mediated by parathyroid hormone (PTH) or to malignancy due to increased osteoclastic activity or a paraneoplastic process secondary to the production of a PTH-related peptide; the latter is the most common in the ED.
The classic ECG finding is shortening of the QT interval, the opposite of that seen in hypocalcemia. This finding occurs because the refractory period after the action potential is shortened. In general, life-threatening dysrhythmias are rare with isolated hypercalcemia, unless they are coupled with concomitant hyperkalemia. Hyperkalemia may be due to the loss of renal concentrating ability secondary to the elevated Ca levels and resultant dehydration with prerenal failure or the renal insult from the deposited Ca in the tubules that leads to direct renal injury and, ultimately, renal failure. Cardiac conduction abnormalities may also occur, with bradydysrhythmias being the most common.
Patients with hypercalcemia (total Ca levels generally 14-16 mg/dL) typically present with weakness, lethargy, and confusion. Significant hypercalcemia (usually with Ca level >15 mg/dL) may present with stupor and coma. A mnemonic often used to characterize the signs and symptoms of hypercalcemia is "stones, bones, moans, and groans," indicating renal calculi, osteolysis and resultant bone pain, psychiatric disorders (eg, depression), and abdominal pain (due to peptic ulcer disease, pancreatitis, and constipation). Hypercalcemia should be suspected in any patient with metastatic bone disease, especially if the primary cancer involves the lungs, breast, or kidneys, as well as in patients with a combination of medical problems, such as kidney stones, pancreatitis, and peptic ulcer disease.
Treatment of hypercalcemia is generally based on the clinical signs and not on a specific absolute serum level, though empiric therapy is often initiated for Ca levels greater than 14 mg/dL. The mainstay of treatment is intravenous volume repletion with normal saline 200-500 mL/h and intravenous bisphosphonate therapy (inhibition of osteoclastic bone resorption). A diuretic may be added as an adjunct to promote calciuresis and volume overload if the patient is euvolemic or if he or she has been adequately rehydrated. Because of their Ca-sparing effect, thiazide diuretics should be avoided. Loop diuretics, such as furosemide, can be used.
81%, positive predictive value [PPV] = 43%); for this purpose, RaVR was better than a QRS interval of 0.010 s (sensitivity = 82%, PPV = 35%).
Calcitonin, a naturally occurring hormone that prevents bone resorption and increases Ca excretion, can be added, though its effect is often short lived. Other slower-acting agents should also be used. Plicamycin (Mithracin), another osteoclast inhibitor, was the mainstay of therapy for hypercalcemia of malignancy; however, bisphosphonates have largely replaced it because of their favorable adverse-effect profile. Gallium nitrate is approved in the United States for treatment of hypercalcemia of malignancy, but the need for continuous intravenous administration over 5 days limits its use. Hydrocortisone and other steroids do not directly treat hypercalcemia, but they have been used in some cases related to vitamin D toxicity and in specific malignancies (sarcoid, multiple myeloma, and some lymphomas); results have been mixed.
Hemodialysis may be required in refractory cases, especially in patients with renal failure, hyperkalemia, or congestive heart failure (when large volumes of saline are contraindicated). Attention must be paid to the treatment of the specific cancer and to end-of-life issues, as the prognosis of a patient with hypercalcemia in malignancy can be dismal.
For more information on hypercalcemia, see Hypercalcemia (within the Internal Medicine specialty) and Hypercalcemia (within the Emergency Medicine specialty).
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