A recent trial published in the New England Journal of Medicine shed light on the challenging diagnosis of arginine vasopressin (AVP) deficiency versus primary polydipsia, a puzzle in the field of water balance disorders. The study involved 158 adult patients and compared the diagnostic accuracy of two stimulation methods: hypertonic saline and arginine.
Out of the participants, 44% received a diagnosis of AVP deficiency, while 56% were diagnosed with primary polydipsia. The diagnostic accuracy was notably higher with hypertonic saline–stimulated copeptin (95.6%) compared to arginine-stimulated copeptin (74.4%). The estimated difference of -21.2 percentage points emphasizes the superiority of hypertonic saline in diagnosing AVP deficiency.

Interestingly, 72% of the participants expressed a preference for arginine testing over hypertonic saline, indicating a potential shift in the landscape of diagnostic preferences.
Adverse events associated with both tests were generally mild. Notably, arginine-stimulated copeptin at or below 3.0 pmol per liter demonstrated a specificity of 90.9% for diagnosing AVP deficiency. Conversely, levels exceeding 5.2 pmol per liter led to a diagnosis of primary polydipsia with a specificity of 91.4%.
These findings carry significant clinical implications, suggesting that hypertonic saline–stimulated copeptin is the preferred method for accurately diagnosing AVP deficiency in adult patients with polyuria polydipsia syndrome. The results underscore the need for a nuanced approach to water balance disorders and provide clinicians with valuable insights into optimizing diagnostic protocols.
This trial marks a crucial step forward in refining diagnostic approaches for water balance disorders, potentially revolutionizing the way AVP deficiency is identified and managed. The study calls for a reassessment of current diagnostic paradigms, with hypertonic saline emerging as the frontrunner in accuracy and patient preference.
Source:
Refardt, J., Atila, C., Chifu, I., Ferrante, E., Erlic, Z., Drummond, J. B., Indirli, R., Drexhage, R. C., Sailer, C. O., Widmer, A., Felder, S., Powlson, A. S., Hutter, N., Vogt, D. R., Gurnell, M., Soares, B. S., Hofland, J., Beuschlein, F., Fassnacht, M., … Christ-Crain, M. (2023). Arginine or Hypertonic Saline–Stimulated Copeptin to Diagnose AVP Deficiency. In New England Journal of Medicine (Vol. 389, Issue 20, pp. 1877–1887). Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2306263