Normal Serum Urate Levels Do Not Rule Out Gout Diagnosis
A normal serum urate level does not exclude the diagnosis of gout, as serum urate levels may be normal during acute gout attacks and do not reliably confirm or exclude the disease. 1, 2
Relationship Between Serum Urate and Gout Diagnosis
While hyperuricemia is the most important risk factor for gout, serum uric acid levels do not confirm or exclude gout diagnosis because many people with hyperuricemia never develop gout, and during acute attacks, serum levels may be normal 1
Demonstration of monosodium urate (MSU) crystals in synovial fluid or tophus aspirates permits a definitive diagnosis of gout, regardless of serum urate levels 1
Studies have shown that approximately 14-63% of patients may have normal serum urate levels (<6 mg/dL) during acute gout attacks 3, 4
Mechanisms Behind Normal Urate Levels During Gout Attacks
Serum urate behaves as a negative acute phase reactant, being temporarily lowered during episodes of acute inflammation and stress 2
Increased renal excretion of uric acid during acute episodes is suggested as the mechanism for this temporary reduction in serum urate levels 2, 4
One study found that 55% of patients with acute gout and normal serum urate levels had increased urinary excretion of uric acid 4
Clinical Implications for Diagnosis
For typical presentations of gout (such as recurrent podagra with hyperuricemia), a clinical diagnosis alone is reasonably accurate but not definitive without crystal confirmation 1
A routine search for MSU crystals is recommended in all synovial fluid samples obtained from undiagnosed inflamed joints to establish a definitive diagnosis 1
Identification of MSU crystals from asymptomatic joints may allow definite diagnosis in intercritical periods when serum urate levels may be misleading 1
Management Considerations
Despite normal serum urate levels during an acute attack, the therapeutic target for long-term management remains a serum urate level <6 mg/dL (<360 mmol/L) to prevent future attacks 1
In patients with severe gout, such as those with tophi or frequent attacks, the target should be a serum urate level <5 mg/dL (<300 mmol/L) until clinical remission is achieved 1
Patients who achieve serum urate levels below 6 mg/dL have significantly lower risk of acute gout attacks (approximately 5%) compared to those with higher levels (10-15%) 1, 5
Common Pitfalls and Caveats
Relying solely on serum urate levels for diagnosis may lead to misdiagnosis, especially during acute attacks when levels may be normal 2, 3
Even when serum urate levels are below the theoretical saturation point of 6.8 mg/dL, gout attacks can still occur due to persistence of tophi and an increased body uric acid pool 3
The timing of serum urate measurement is important - levels are more reliable for diagnostic purposes when measured between attacks rather than during acute flares 2
Patients on allopurinol therapy may have lower serum urate levels during acute attacks compared to those not on urate-lowering therapy, further complicating the diagnostic picture 3