Endocrine Abstracts

Background: Differential diagnosis of hyponatremia is challenging, particularly for thiazide associated hyponatremia (TAH), as patients might have either volume depletion in need for fluid substitution or syndrome of inappropriate antidiuresis (SIAD)-like presentation requiring fluid restriction. Urine indices are of little utility, because they are influenced by thiazide therapy. Apparent strong ion difference (aSID) describes the relation between sodium, potassium and chloride in serum and is used in evaluation of acid-base disorders according to Stewart model. aSID could help in the differential diagnosis of TAH because a value >40 identifies patients with contraction alkalosis due to relative hypochloremia, and hypochloremic alkalosis is a well-known possible adverse effect of thiazide diuretics.

Material and Methods: This was a post-hoc analysis of prospectively collected data of hospitalized patients with hypotonic hyponatremia <125 mmol/l. TAH patients were divided according to treatment response in patients needing intravenous fluid substitution or fluid restriction. Treatment response was defined as a sodium increase of at least 4 mmol/l/die or >130 mmol/l based on chart review. aSID at baseline was calculated with the formula serum sodium plus potassium minus chloride and a value >40 was used to identify volume-depleted TAH patients. Descriptive analysis was carried out to find differences between volume-depleted and SIAD-like TAH patients, and patients with SIAD without thiazide use. Logistic regression and ROC curves were computed to investigate the role of aSID>40 for differential diagnosis of hyponatremia in TAH patients, in addition to known factors for identifying SIAD patients as body mass index (BMI) and fractioned uric acid excretion (FUA) with the previous described cut-off of 12%.

Results: Out of 303 hyponatremia patients, 131 (43.2%) had a TAH and 75 (24.8%) SIAD without thiazide use. Among TAH patients, 81 (61.8%) were successfully treated with fluid substitution and 31 (23.7%) with fluid restriction. 19 patients (14.5%) were excluded as they received no treatment, or needed to switch treatment during hospitalization. No differences in baseline characteristics were seen between patients with SIAD and SIAD-like TAH patients, except for BMI, lower in SIAD patients (mean(SD) 23.5(5.1) vs 27.0(5.7) kg/m2, P=0.003). A higher BMI and a FUA<12% had a sensitivity of 84% with a specificity of 60% in identifying volume-depleted TAH patients. Adding aSID>40 improved the specificity to 74% maintaining a sensitivity to 82%.

Conclusion: In hospitalized patients with TAH, calculation of aSID may help differentiating patients with volume depletion in need of fluid substitution from SIAD-like manifestation requiring fluid restriction.