Background: The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia. Its diagnosis requires decreased serum osmolality, inappropriately diluted urine (e.g. >100 mosm/kg), clinical euvolemia, and a urinary sodium excretion (U-Na) >30 mmol/L. In hyponatremic patients taking diuretics, however, this definition is unreliable due to the natriuretic effect of diuretics. Here we examined the diagnostic potential of alternative laboratory measurements to diagnose SIAD irrespective of the use of diuretics.

Methods: 86 consecutive hyponatremic patients (serum sodium <130 mmol/L) were classified based on their history, clinical evaluation, osmolality, and saline response to isotonic saline into a SIAD and a non-SIAD group. U-Na, serum urate concentration, fractional excretion (FE) of sodium, urea, and uric acid were measured in all subjects. The accuracy to diagnose SIAD was assessed using ROC analysis.

Results: Thirty-one patients (36%) had a diagnosis of SIAD and 55 patients (64%) were classified as non-SIAD. 57 patients (68%) were on diuretics (15 in the SIAD group, 42 in the non-SIAD group). In the absence of diuretic therapy, SIAD was accurately diagnosed using U-Na (area under the ROC curve [AUC] 0.96; 0.92-1.02). However, in patients on diuretics the diagnosis was unreliable (AUC 0.85; 0.73-0.97). There, FE-UA performed best compared to all other markers tested (AUC 0.96; 0.92-1.12) resulting in a positive predictive value of 100% if a cut-off value of 12% was used.

Conclusion: FE-UA allows the diagnosis of SIAD with excellent specificity. Combining the information on U-Na and FE-UA leads to a very high diagostic accuracy in hyponatremic patients with and without diuretic treatment.