Enhancing diagnostic tools for vasopressin deficiency: insights from a single-center cohort study

Context: A recent multicenter trial confirmed that hypertonic saline-stimulated copeptin is superior to the arginine stimulation test (AST) for diagnosing vasopressin deficiency (AVP-D). The latter, though less accurate, is cheaper, better tolerated, and easier to perform. We aimed to improve AST diagnostic accuracy by incorporating additional parameters alongside copeptin. Methods: We retrospectively analysed ASTs from patients evaluated for suspected AVP-D. Final diagnosis was defined based on clinical, biochemical, radiological and follow-up data. We evaluated the test diagnostic accuracy based on either literature reported or ROC-based thresholds of several variables even in combination. Results: Nineteen patients were included and 8 were diagnosed with AVP-D. Copeptin response to AST was flat in AVP-D compared to primary polydipsia (PP) but showed limited discriminatory power with the maximal accuracy for copeptin-based parameters reaching 73.7%. AVP-D patients had lower urinary osmolarity (UOsm) and higher plasma osmolarity and serum sodium (Na) at AST end. Na at AST end was the best predictor of AVP-D (≥ 141 mmol/L: sensitivity 87.5%, specificity 100%, accuracy 94.7%, AUC 0.989). A multistep approach initially assessing Na at AST end and, in dubious cases (140-142 mmol/l), also either copeptin peak (≤ 4.1 pmol/L), UOsm (≤ 428 mOsm/kg), or absent posterior pituitary hyperintense signal achieved 100% diagnostic accuracy. Logistic regression using Na at AST end values combined with any of these aforementioned additional variables also reached complete discrimination between AVP-D and PP. Discussion: Combining multiple parameters after AST improved diagnostic accuracy, even without measuring copeptin. Despite the study's retrospective design, small sample, and absence of hypertonic saline testing, findings support the potential utility of a multivariable approach to AST interpretation.