Symptoms of Tumor Lysis Syndrome
Tumor lysis syndrome presents with a constellation of clinical manifestations including nausea, vomiting, diarrhea, anorexia, lethargy, edema, fluid overload, hematuria, congestive heart failure, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, and possible sudden death, typically occurring within 12 to 72 hours after initiation of cytoreductive therapy. 1
Laboratory Abnormalities
The metabolic derangements that define tumor lysis syndrome include:
- Hyperuricemia (>8 mg/dL in adults) results from massive nucleic acid breakdown and can cause uric acid crystallization in renal collecting ducts, leading to acute oliguric renal failure 1, 2
- Hyperkalemia (≥6 mmol/L) develops from rapid release of intracellular potassium and is life-threatening, producing cardiac irregularities such as arrhythmias, ventricular tachycardia, fibrillation, or cardiac arrest 1, 2
- Hyperphosphatemia (>1.62 mmol/L) occurs from tumor cell lysis and can precipitate with calcium, worsening renal injury 1, 2
- Hypocalcemia results from calcium-phosphate precipitation in tissues and may cause tetany and seizures when symptomatic 1, 2
Laboratory TLS is defined by two or more abnormal serum values (uric acid, potassium, phosphate, or calcium) occurring within 3 days before or 7 days after chemotherapy initiation 1
Clinical Symptoms by System
Cardiac Manifestations
- Palpitations, arrhythmias, ventricular tachycardia, and cardiac arrest from hyperkalemia 1, 3
- Congestive heart failure from fluid overload 1
- Sudden death, with two of four deaths in one Burkitt's lymphoma cohort directly attributable to hyperkalemia 1, 3
Neuromuscular Effects
- Muscle cramps and paresthesias from elevated potassium levels 1
- Tetany and seizures from symptomatic hypocalcemia 1
- Lethargy and syncope 1
Gastrointestinal Symptoms
- Nausea, vomiting, diarrhea, and anorexia are common presenting symptoms 1
Renal Manifestations
- Hematuria, oliguria, and acute renal failure from uric acid crystal deposition 1
- Uremia (abnormally increased blood urea nitrogen) from multiple mechanisms including uric acid crystal deposition, calcium phosphate precipitation, and xanthine crystallization 1
- Edema and fluid overload 1
Timing of Symptom Onset
Symptoms most commonly appear within 12 to 72 hours after initiation of cytoreductive therapy, though they may occur before chemotherapy starts in cases of spontaneous tumor lysis syndrome. 1, 4
Critical Pitfalls
The mortality rate for clinical TLS reaches 83% when significant complications develop, compared to 24% without clinical TLS 3. In solid tumors, mortality approaches 35% due to delayed recognition 2. Hyperkalemia is particularly dangerous, as it can progress rapidly from mild symptoms (muscle cramps, palpitations) to life-threatening arrhythmias and sudden cardiac death 1, 3. Continuous ECG monitoring is mandatory for all patients with hyperkalemia 2, 3.