Signs of Tumor Lysis Syndrome
Tumor lysis syndrome presents with at least 2 of 4 characteristic metabolic abnormalities—hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia—occurring within 3 days before or 7 days after chemotherapy initiation. 1
Laboratory TLS (Biochemical Signs)
Laboratory TLS requires at least 2 of the following 4 metabolic derangements to be present: 2, 1
- Hyperuricemia: Elevated serum uric acid levels due to massive purine release from lysed tumor cells 2, 3
- Hyperkalemia: Elevated potassium from intracellular ion release, which can be life-threatening when ≥6 mmol/L 2, 4
- Hyperphosphatemia: Elevated phosphate levels from tumor cell breakdown 2, 5
- Hypocalcemia: Secondary to calcium-phosphate precipitation as phosphate binds calcium 2, 6
These biochemical abnormalities typically manifest 48-72 hours after initiation of cancer treatment, though they can occur spontaneously in highly aggressive malignancies 6.
Clinical TLS (Life-Threatening Signs)
Clinical TLS is defined as laboratory TLS plus at least one of the following clinical complications: 1
Renal Manifestations
- Acute oliguric renal failure or anuria: Uric acid crystallization in collecting ducts and renal vessels causes acute kidney injury 2
- Decreased urine output: Despite aggressive hydration, indicating uric acid nephropathy 4
- Elevated serum creatinine: >1.5 times upper limit of normal or eGFR ≤60 mL/min 7
Cardiac Manifestations
- Cardiac arrhythmias: Hyperkalemia-induced ECG changes and potentially fatal dysrhythmias requiring continuous ECG monitoring 2, 7
- Hemodynamic instability: From severe electrolyte derangements 2
Neurological Manifestations
- Seizures: From severe hypocalcemia or metabolic encephalopathy 2, 7
- Tetany: Neuromuscular irritability from symptomatic hypocalcemia 2
- Uremic encephalopathy: In severe cases with advanced renal failure 2
Additional Clinical Signs
Metabolic Derangements
- Severe metabolic acidosis: From renal failure and cellular breakdown 3, 5
- Volume overload: Unresponsive to diuretic therapy, indicating need for dialysis 2, 4
Laboratory Markers of High Risk
- Markedly elevated LDH: Can increase up to 17-fold (as high as 87,608 U/L in documented cases), indicating massive tumor lysis 8
- Elevated baseline uric acid: Pre-treatment hyperuricemia >7.5 mg/dL increases risk 7, 8
- Pre-existing azotemia: Baseline renal impairment worsens prognosis 8, 6
Common Pitfalls in Recognition
Asymptomatic hypocalcemia does not require treatment and should not be treated, as calcium administration can precipitate calcium-phosphate crystals in tissues and worsen renal injury 2, 1. Only treat symptomatic hypocalcemia manifesting as tetany or seizures 2.
Mild hyperphosphatemia (<1.62 mmol/L) does not require treatment, though more severe elevations necessitate phosphate binders 2. Hyperphosphatemia-induced acute renal failure from intrarenal calcium-phosphate precipitation can occur even during appropriate therapy 5.
The mortality rate for TLS in solid tumors approaches one in three patients when not prevented, emphasizing the critical importance of early recognition 8. Risk is highest in patients with bulky disease, elevated LDH, pre-existing renal impairment, and highly chemotherapy-sensitive tumors 9, 1, 8.