The actual reference range of serum uric acid has been assessed according to its variations among healthy individuals. i.e. those without clinical evidence of gout. By this approach, serum uric acid values between 3.5 and 7.2 mg/dL in adult males and postmenopausal women and between 2.6 and 6.0 mg/dL in premenopausal women have been identified as normal in many countries. However, this definition of normal range of serum uric acid in the general population is inevitably influenced by what we consider as "normal", since the absence of gout flares does not necessarily imply the absence of uric acid-related damage. Indeed, a growing body of evidence indicates that silent deposition of monosodium urate crystals as a result of hyperuricaemia may occur and lead to early destructive skeletal changes. In addition, a growing body of evidences demonstrates that uric acid might play a pathophysiological role in many "cardio-nephro-metabolic" disorders, which seems to be independent of the deposition of monosodium urate crystals, since it is evident also for serum uric acid concentrations below the saturation point for monosodium urate. Taken together, these findings strongly suggest to carefully reconsider the concept of "asymptomaticity" for chronic hyperuricemia and to consequently revise the normal range of serum uric acid levels also considering the progressive worldwide increase of circulating levels of uric acid, which could lead to a "shift to right" (i.e. toward higher values) of normal range. In the light of the new scientific knowledge on the pathophysiological role of uric acid in human disease, a threshold value < 6.0 mg/dL (< 360 µmol/L) seems to better identify true "healthy subjects" and should reasonably be considered for all subjects.
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