Spontaneous Tumor Lysis Syndrome
A 61-year-old man with high-grade non-Hodgkin lymphoma and bulky lymphadenopathy was to start chemotherapy the following week. He had poorly controlled type 2 diabetes. He was found collapsed at home and died. Blood on arrival showed potassium 7.4 mmol/L, uric acid 16 mg/dL, phosphate 2.6 mmol/L, corrected calcium 1.7 mmol/L, creatinine 310 µmol/L and lactate dehydrogenase 2100 U/L. Which of the following is the most likely cause of death?
- A.Drug-induced nephropathy
- B.Spontaneous tumor lysis syndromeCorrect
- C.Undiagnosed diabetic nephropathy
- D.Distal renal tubular acidosis
Explanation
The biochemical quartet of hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia with acute kidney injury and a very high lactate dehydrogenase defines tumor lysis syndrome. Although it is usually seen 12 to 72 hours after starting cytotoxic therapy, it can occur spontaneously before any treatment in tumors with a very high proliferative rate and large burden, classically Burkitt lymphoma and other high-grade non-Hodgkin lymphomas, as well as acute leukemias with high white cell counts. Massive cell turnover releases intracellular potassium, phosphate and nucleic acids; the nucleic acids are catabolized to uric acid, which precipitates in the renal tubules, while calcium phosphate deposition causes both further nephrocalcinosis and secondary hypocalcemia. Death results from hyperkalemic cardiac arrhythmia, and the elevated creatinine reflects urate and phosphate nephropathy rather than chronic disease. Diabetic nephropathy of long standing would produce a chronic rise in creatinine with proteinuria and possibly hyperkalemia, but not marked hyperuricemia with hyperphosphatemia and hypocalcemia appearing acutely alongside a lactate dehydrogenase of 2100 U/L. A drug-induced nephropathy would likewise not generate this specific electrolyte pattern, and no nephrotoxic exposure is described. Distal renal tubular acidosis characteristically causes hypokalemia with a normal anion gap acidosis and nephrolithiasis, the opposite potassium abnormality. Prevention in high-risk patients relies on aggressive intravenous hydration with allopurinol, or rasburicase where the urate load is high, plus close biochemical monitoring and early dialysis for refractory hyperkalemia or oliguria.
Why each option
- A.
- No nephrotoxic drug exposure is described, and drug-induced injury would not produce hyperuricemia with hyperphosphatemia and hypocalcemia.
- B.
- Correct. Hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia with a high lactate dehydrogenase in bulky high-grade lymphoma indicate spontaneous tumor lysis syndrome.
- C.
- Chronic diabetic nephropathy causes a gradual creatinine rise with proteinuria and does not explain the acute metabolic profile.
- D.
- Distal renal tubular acidosis typically causes hypokalemia with a normal anion gap acidosis, not hyperkalemia with hyperuricemia.
Reference: UpToDate 2025, Tumor lysis syndrome: Prevention and treatment
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