The aim of this study is to evaluate whether a new test using mannitol infusion can diagnose the cause of polyuria-polydipsia syndrome as accurately as the current standard test (hypertonic saline infusion) and to compare which test patients prefer. The goal is to identify a simpler and more patient-friendly diagnostic approach.
Age ≥ 18 years
Hypotonic polyuria/polydipsia syndrome defined as polyuria >40ml/kg body weight/24h and polydipsia >3l/24h; and urine osmolality <800mOsm/L or known AVP-D based on accepted criteria
Polyuria/polydipsia secondary to diabetes mellitus, hypercalcemia, or hypokalemia
Diagnosis of AVP-R (Copeptin > 21.4 pmol/L)
Evidence of acute illness
Epilepsy requiring treatment
Crossover
Mannitol
Diagnostic testIntravenous infusion of 1.5g/kg body weight (max. 120g) mannitol is given over 30 minutes (≙ 7.5ml/kg body weight).
Hypertonic Saline
Diagnostic testIntravenous infusion of NaCl 3% is given first as a bolus of 250ml over 15 minutes, then with an infusion rate of 0.15ml/kg body weight / minute (≙ 9ml/kg body weight/hour).
Overall Diagnostic Accuracy
The overall diagnostic accuracy is defined as the proportion of correct diagnoses out of all diagnoses based on the stimulated copeptin value. Final diagnosis will be made after termination of the study by two endocrine specialists who will be blinded to the copeptin results of the mannitol infusion.
Patient Test Preference
Patient-reported preference between mannitol infusion and hypertonic saline infusion, assessed using a 5-point Likert scale ranging from -2 (strong preference for hypertonic saline) to +2 (strong preference for mannitol).
Diagnostic Performance Measures for AVP-D
Sensitivity, specificity, positive predictive value, and negative predictive value of mannitol infusion and hypertonic saline infusion for diagnosing AVP deficiency using predefined copeptin cut-offs.
Diagnostic Performance Measures for PP
Sensitivity, specificity, positive predictive value, and negative predictive value of mannitol infusion and hypertonic saline infusion for diagnosing PP using predefined copeptin cut-offs.
Optimal copeptin cut-off after mannitol infusion
Exploratory determination and validation of optimal copeptin cut-off values for differentiating AVP deficiency from primary polydipsia following mannitol stimulation.
Frequency and severity of clinical symptoms
Frequency and severity of symptoms (e.g., thirst, headache, nausea, malaise) assessed using numeric rating scales during mannitol and hypertonic saline tests.
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