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Abstract: PO1876

Cerebral Salt Wasting Caused by High-Dose Methotrexate

Session Information

Category: Onco-Nephrology

  • 1500 Onco-Nephrology


  • Shahoori, Neda, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
  • Samiratedu, Michael M., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
  • Chavez Morales, Efren Alejandro, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States

Severe acute hyponatremia is a rare complication of high-dose methotrexate (HDMTX) use.

Case Description

We present an interesting case of a 54 year-old man with relapsed diffuse large B-cell lymphoma with central nervous system (CNS) involvement who received a chemotherapy regimen including HDMTX. He received a single dose of 7.2 g of intravenous HDMTX. Baseline serum sodium (Na) was 140 mmol/L. Within 48 hours serum Na dropped to 120 mmol/L and patient developed mild headache and confusion. Laboratory evaluation revealed a urine Na 245 mmol/L, fractional excretion of sodium (FeNa) 2.5%, urine potassium 47 mmol/L and urine osmolality 561 mOsm/kg. Serum tests showed Na 120 mmol/L, chloride 81 mmol/L, osmolality 245 mOsm/kg, uric acid 2.5 mg/dL, TSH 0.6 uIU/mL, cortisol level 15 microg/dL, creatinine 0.6 mg/dL and a low serum ADH level (<0.8 pg/mL). Rest of serum electrolytes were within normal limits. Patient was polyuric and soon became hypotensive and tachycardic. He was treated with a combination of 3% hypertonic saline and oral loop diuretics with subsequent improvement in symptoms, increase in serum sodium and reduced natriuresis.


We hypothesize a case of cerebral salt wasting due to the toxic neurologic effect of HDMTX in a vulnerable patient with an underlying CNS tumor. HDMTX has been associated with toxicity to neurosecretory aspects of the cerebrum which may lead to activation of CNS natriuretic peptides which are thought to be responsible for fluid regulation. There are multiple literature reports about cases of subarachnoid hemorrhage, strokes or seizures who developed hyponatremia originally thought to be due to SIADH, but then attributed to stimulation of CNS natriuretic peptides. We did not measure a serum B-type natriuretic peptide (BNP) in our patient, however serum ADH level was low. BNP was initially called brain natriuretic peptide because it was first found in brain tissue. However, BNP is produced primarily by myocardial cells of the left ventricle in response to stretch. The primary natriuretic peptides of the CNS are thought to be C-type natriuretic peptide and D-type natriuretic peptide, which have been shown to induce natriuresis leading to hyponatremia and suppressed ADH levels, as was possibly seen in our patient. We report this case to allow clinicians to be aware of this possible occurrence.