Hyponatremia in a patient with cryptococcal meningitis: syndrome of inappropriate antidiuretic hormone (SIADH) or cerebral salt wasting (CSW)?

An 83-year-old man admitted for weakness, lethargy, and mental status changes was found to have human immunodeficiency virus (HIV) disease and cryptococcal meningitis. His hospital course was complicated by worsening hyponatremia (sodium < 136 mEq/L). By hospital day 6, the patient’s serum sodium had declined to 127 mEq/L from his admission level of 133 mEq/L. The initial impression was that the patient had syndrome of inappropriate antidiuretic hormone (SIADH) and fluid restriction to less than 1500 mL per day was initiated. By hospital day 11, serum sodium continued to decline, to 123 mEq/L, despite fluid restriction. The past medical history was remarkable for coronary artery disease, hypertension, hyperlipidemia, and anemia, but by self-report he had not been taking any medications. His review of systems was positive for intermittent bouts of diarrhea. Vital signs on day 11 included a temperature of 37.3 C, blood pressure (BP) of 105/55 mm Hg, and pulse of 90 beats per minute. The BP on admission had been 145/86 mm Hg but had steadily declined with fluid restriction. On physical examination, he appeared thin and cachetic with no evidence of jugular venous distention, rales, or peripheral edema to suggest volume overload. He had been receiving 2 to 4 L of isotonic saline daily for 5 days before the fluid restriction was initiated. The urine output continuously exceeded his intake by at least 500 mL per day throughout his hospital course. His only inpatient medications were amphotericin B and flucytosine. For nutritional supplementation, he was receiving a high-calorie supplement with free-water flushes via a nasogastric tube. Laboratory results revealed a serum sodium concentration of 123 mEq/L, serum potassium of 4.4 mEq/L, serum creatinine of 0.6 mg/dL, urine sodium of 139 mEq/L, serum osmolality of 272 mOsm/kg, and urine osmolality of 598 mOsm/kg (see Table 1). Urinalysis revealed a specific gravity of 1.030. A random serum cortisol level was 11.1 lg/dL. A thyroid-stimulating hormone (TSH) level was 1.32 lIU/mL. Brain natriuretic peptide (BNP) was elevated, at 686 pg/mL. A fractional excretion of uric acid was also elevated, at 83.8%. The clinical assessment was volume depletion given the high urine specific gravity, decreasing BP, and a negative fluid balance. The hyponatremia was determined to be due to sodium loss rather than dilution from inappropriate antidiuretic hormone secretion. Intravenous fluid (IVF) hydration with isotonic saline was initiated with a goal to keep the patient in positive fluid balance. The serum sodium level gradually improved to 140 mEq/L over the next 10 days. Attempts to decrease the rate of IVF resulted in a fall in serum sodium and improved when isotonic saline was increased. Eventually, the patient was placed on fludrocortisone, which normalized his urine output and serum sodium. The response to the treatment regimen supported our diagnosis of cerebral salt wasting (CSW). The patient’s serum sodium concentration upon discharge was 135 mEq/L.