Redefining Diagnostic Cut-Offs for the Indirect Water Deprivation Test

Objective: An incorrect diagnosis of arginine vasopressin deficiency and resistance (AVP-D and AVP-R) results in the potentially dangerous use of desmopressin in healthy individuals. The water deprivation test is a central diagnostic test in patients with polydipsia polyuria syndrome (PPS). This study aims to determine the effectiveness of the current interpretation of reference ranges.

Methods: This is a retrospective analysis of 135 patients who underwent a water deprivation test between August 2014 and August 2023. All patient diagnoses were reviewed, and variability and receiver operating characteristic (ROC) curves were determined for serum osmolality, serum sodium and urine osmolality.

Results: Serum sodium demonstrated reduced variability compared with serum osmolality (0.72% vs. 1.16%, respectively, 37.5% reduction; p < 0.001). The standard serum osmolality cut-off value of ≥ 300 mOsm/kg in diagnosing AVP-D, AVP-R, and primary polydipsia (PP) achieved a sensitivity of 76.19% and specificity of 76.92%. A serum sodium cut-off value of ≥ 148 mmol/L demonstrated 100% specificity in excluding PP. This cut-off was used alongside urine osmolality cut-off values of > 630 mOsm/kg (for PP) and < 383 mOsm/kg (for AVP-D/AVP-R). Review of post-desmopressin urine osmolality and clinical monitoring was performed in equivocal diagnostic cases (n = 6), achieving 100% sensitivity and 100% specificity within the study sample.

Conclusions: This study demonstrates that a serum sodium cut-off of ≥ 148 mmol/L in tandem with urine osmolality yields the best diagnostic accuracy to differentiate between AVP-D, AVP-R, and PP. Serum sodium may be more reliable than serum osmolality in the investigation of patients with PPS, demonstrating lower biological and analytical variability.