Use of Copeptin Measurement after Arginine Infusion for the 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 discomfort for patients due to the rise in plasma
sodium levels above 149mmol/l and requires the presence of medical staff at all
times for controls of plasma sodium levels.
The arginine stimulation test is routinely used to stimulate growth hormone.
Own data in 96 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 93% and
the infusion is generally well tolerated.
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.

The primary objective of this prospective international multicenter diagnostic
study is the comparison of the diagnostic accuracy between copeptin measurement
after arginine-stimulation (CAS) and the current best diagnostic test copeptin
measurement after hypertonic saline infusion (HIS) in the differential
diagnosis of diabetes insipidus

diagnostic study

A) Arginine infusion test
Intravenous infusion of 0.5 g / kg body weight (max. 40 g) L-Arginine
Hydrochlorid (21%) diluted in 500 ml NaCl 0.9% is administered for 30 minutes.
Blood samples for later copeptin measurement are collected before, 60 and 90
minutes after the start of the infusion

B) 3% NaCl infusion test
Intravenous infusion of NaCl 3% is first given as a bolus of 250 ml for 15
minutes, then with an infusion rate of 0.15 ml per kg body weight per minute
until the sodium content in plasma has risen to> 149 mmol / l. Plasma copeptin
is measured at this point. Once the measurement is complete, patients should
drink at least 30 ml / kg body weight within 60 minutes while simultaneously
administering 5% 500 ml glucose to ensure that plasma sodium levels fall within
the normal range.

The infusion with arginine is also used in children and adults to stimulate
growth hormone and has no relevant side effects. Rarely, nausea and a low level
of discomfort have been reported during the infusion.

The most common symptoms during the 3% NaCl infusion test were thirst, moderate
headache, and moderate malaise. All symptoms are to be expected due to
hypertonic stimulation and immediately improved after discontinuation of the
infusion.

According to the information provided above, we consider the risk of this
diagnostic test to be small. For safety reasons, patients with epilepsy,
uncontrolled arterial hypertension, heart failure, cirrhosis of the liver or
unadjusted adrenal or thyroid deficiency are excluded from participation.