Therapy usually is initiated with isotonic saline intravenously. This restores blood volume and increases urinary calcium excretion. The aim is to maintain urine output in adults at 100 to 150 mL/hour. If the patient is fluid overloaded initially, a loop diuretic such as furosemide, which inhibits passive resorption of sodium, may be given. Patients should be monitored for hypomagnesemia, hypokalemia, and hypovolemia if a loop diuretic is given. Medications such as thiazide diuretics, which increase serum calcium, should be avoided.

Bisphosphonates inhibit calcium release by interfering with osteoclast-mediated bone resorption.⁵ Their maximum effect occurs in 2 to 4 days, and they are usually given with saline as above and possibly calcitonin.^2,6 Pamidronate, 60 to 90 mg IV over several hours, or zoledronic acid, 4 mg IV over at least 15 minutes, are recommended doses.² These medications can cause impaired renal function, hypophosphatemia, and osteonecrosis of the jaw.⁷

Calcitonin increases renal calcium excretion and decreases bone resorption. In intramuscular or subcutaneous doses of 4 IU/kg, salmon calcitonin works rapidly to lower serum calcium by 1 to 2 mg/dL within 4 to 6 hours.⁸ Glucocorticoids such as hydrocortisone, 100 mg IV every 6 hours, can be useful if the hypercalcemia is related to elevated levels of vitamin D, as in Hodgkin disease and some other lymphomas. Treatment of the underlying malignancy can control the hypercalcemia. As treatments of last resort, hemodialysis and peritoneal dialysis are effective therapies for hypercalcemia.^9,10

Syndrome of Inappropriate Antidiuretic Hormone

In patients with cancer, the syndrome of inappropriate antidiuretic hormone (SIADH) is a paraneoplastic syndrome resulting from the secretion of arginine vasopressin (also known as antidiuretic hormone [ADH]). The increased production of ADH results in a characteristic constellation of chemical abnormalities including hypo-osmolality, hyponatremia, and an inappropriately elevated urine osmolality, generally above 100 mOsm/kg. Urine sodium is usually above 40 mEq/liter. Potassium levels are typically unaffected, and acid-base balance should be normal unless there are confounding factors.^11,12

SIADH can result from many causes such as stroke, hemorrhage, infection, or other CNS disorders that can enhance ADH release. When due to ectopic production of ADH by a tumor, the cause is most often small cell carcinoma of the lung (and can occur in up to 10% of small cell carcinoma lung patients). However, other cancers of the head and neck, pancreas, and duodenum can be responsible.^13,14

The increase in ADH is usually the result of secretion of vasopressin by certain tumors, resulting in increased water resorption in the collecting ducts of the kidneys and an increased loss of sodium in the urine. Some drugs can enhance ADH release or effect, notably the chemotherapy drugs vincristine and cyclophosphamide.¹⁵ Recent chemotherapeutic agents should be reviewed, along with a search for CNS disease or pulmonary disease, especially pneumonia, asthma, atelectasis, and pneumothorax.16 There should not be other reasons for normovolemic hyponatremia such as diuretic therapy, preexisting renal disease, adrenal insufficiency, or hypothyroidism.