Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study

Use of Copeptin Measurement After Arginine Infusion for the Differential Diagnosis of Diabetes Insipidus - the CARGOx Study

The differential diagnosis of central diabetes insipidus (cDI) is difficult and the current test with the highest diagnostic accuracy is copeptin measurement after hypertonic saline infusion (HIS). Although the HIS improved diagnostic accuracy compared to the standard water deprivation test used for decades before, it still comprises great discomfort for patients due to the rise in serum sodium levels above 149mmol/l and requires the presence of medical staff at all times to guarantee safety of the test.

The arginine stimulation test is routinely used to stimulate growth hormone. Own data in 52 patients with polyuria / polydipsia syndrome showed that arginine infusion is a potent stimulator of the neurohypophysis and provides a new diagnostic tool in the differential diagnosis of cDI. Copeptin measurements upon arginine stimulation (CAS) discriminated patients with diabetes insipidus vs. patients with primary polydipsia with a high diagnostic accuracy of 94%.

To validate these results and to compare them against the HIS a large multicenter trial is needed, where the diagnostic accuracy of the CAS is compared to the HIS.

Inclusion Criteria:

• Age ≥ 18 years
• Hypotonic polyuria / polydipsia syndrome defined as: polyuria >50ml/kg body weight/24h and polydipsia >3l /24h or known diabetes insipidus under treatment with DDAVP
• Urine-Osmolality <800mOsm/L

Exclusion Criteria:

• Polyuria / polydipsia secondary to diabetes mellitus, hypercalcemia or hypokalemia
• Nephrogenic diabetes insipidus (defined as baseline copeptin level >21.4pmol/L)
• Evidence of any acute illness
• Epilepsy requiring treatment
• Uncontrolled arterial hypertension (blood pressure >160/100mmHg at baseline)
• Cardiac failure (NYHA III-IV)
• Liver cirrhosis (Child B-C)
• Uncorrected adrenal or thyroidal deficiency
• Patients refusing or unable to give written informed consent
• Pregnancy or breast feeding
• End of life care