Copeptin in the differential diagnosis of hypotonic polyuria



Copeptin is secreted in equimolar amount to Arginine Vasopressin (AVP) but can easily be measured with a sandwich immunoassay. Both peptides, copeptin and AVP, show a high correlation. Accordingly, copeptin mirrors the amount of AVP in the circulation and its measurement provides an attractive marker in the differential diagnosis of diabetes insipidus.

The polyuria polydipsia syndrome

Diabetes insipidus—either central or nephrogenic—has to be differentiated from primary polydipsia. Differentiation is crucial since wrong treatment can have deleterious consequences. Since many decades, the “gold standard” for differential diagnosis has been the classical water deprivation test, which has several limitations leading to an overall limited diagnostic accuracy. In addition, the test has a long duration of 17 hours and is cumbersome for patients. Clinical signs and symptoms as well as MRI characteristics overlap between patients with diabetes insipidus and primary polydipsia. Direct measurement of AVP upon osmotic stimulation was first shown to overcome these limitations, but failed to enter clinical practice mainly due to technical limitations of the AVP assay.

Copeptin as diagnostic tool in the polyuria polydipsia syndrome

We have recently shown that copeptin, without prior water deprivation, identifies patients with nephrogenic diabetes insipidus. On the other hand, for the more difficult differentiation between central diabetes insipidus and primary polydipsia, a copeptin level of 4.9 pmol/L stimulated with hypertonic saline infusion differentiates between these two entities with a high diagnostic accuracy, and is superior to the water deprivation test. It is important to note that close sodium monitoring during the hypertonic saline test is a prerequisite.


Therefore, we propose that copeptin upon hypertonic saline infusion should become the new standard test in the differential diagnosis of diabetes insipidus.

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Fig. 1

Adapted from [8]

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Fig. 3

Modified from [14].

Fig. 4

Modified from [61]


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M. Christ-Crain was supported by a grant from the Swiss National Science Foundation (SNF-162608) and the University Hospital Basel, Switzerland.

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Correspondence to M. Christ-Crain or W. K. Fenske.

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MCC and WF received speaker honoraria from Thermofisher AG, the manufacturer of the Copeptin assay.

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Christ-Crain, M., Fenske, W.K. Copeptin in the differential diagnosis of hypotonic polyuria. J Endocrinol Invest 43, 21–30 (2020).

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  • Diabetes insipidus
  • Primary polydipsia
  • Differential diagnosis