New Diagnostic Test Accurately Differentiates Diabetes Insipidus From Polyuria Polydipsia Syndrome


The new test should replace the water deprivation test as the new standard of care, investigators say.

Prof. Mirjam Christ-Crain, MD, PhD

Investigators from the University of Basel and University Hospital Basel, in Switzerland, have found a better way to test for diabetes insipidus than the previously-used and oft-unpleasant water deprivation test.

In diabetes insipidus, pituitary glands lack the hormone vasopressin, therefore, leading to a salt content disregulation in the body. Without the ability to concentrate their urine, patients lose a lot of fluid and have to drink water constantly to prevent dehydration.

Of course, drinking water is recommended, but drinking a lot of water is rarely a remarkable feat. Drinking by the liter—a condition known as polyuria-polydipsia syndrome—can be part of a daily habit, or even stem from mental illness, but is different from diabetes insipidus due to the vasopressin deficiency.

Previously, the only way to differentiate between the 2 conditions was by using a water deprivation test, which prohibits a patient from drinking any liquid for 16 hours. After that period of time, doctors would interpret the patient’s urine. However, the test has often been considered to be misleading, with physicians having to correct diagnoses in about half of the cases they used the test for.

For their study, published in the New England Journal of Medicine, the investigators sought to compare the water-deprivation test with a new diagnostic method which featured direct detection of the biomarker plasma copeptin, a precursor-derived surrogate of vasopressin.

To do this, the investigators recruited 156 patients with hypotonic polyuria at 11 medical centers. A total of 144 patients underwent the water-deprivation and hypertonic saline infusion tests. After the latter test was given, the investigators measured the concentration of copeptin in the patients’ blood.

“The most surprising observation is that the new test has a much higher diagnostic accuracy to differentiate 2 diverse diseases: diabetes insipidus and primary polydipsia, as compared to the classical water deprivation test (which has been done for decades as gold standard),” Professor Mirjam Christ-Crain, MD, PhD, told Rare Disease Report®. “The hypertonic saline plus copeptin test should, therefore, replace the ‘old’ test as the new gold standard.”

Although the water deprivation test determined the correct diagnosis with 76.6% accuracy, the copeptin test had a 97% rate of correct diagnoses. The investigators said that this allowed patients to receive faster treatment. Of the 144 patients that underwent both tests, 62 patients had forms of diabetes insipidus and 82 patients had polydipsia.

“Implications for physicians are, therefore, that they should perform the new test, in order to correctly diagnose their patients,” Prof. Christ-Crain continued, adding that the new test is now available for clinical use. “A correct diagnosis is very important since treatment between the different entities differs: Patients with diabetes insipidus are treated with a vasopressin analogue, whereas patients with primary polydipsia are treated with fluid restriction. The wrong treatment in each of these patient groups can have deleterious complications—such as water intoxication if e.g. patients with primary polydipsia are wrongly treated with vasopressin analogues.”

In a related editorial, a duo from the Tufts University School of Medicine and the Maine Medical Center Research Institute pointed out that the patients whose diagnosis was misclassified in the study with the water deprivation test received the correct diagnosis after completing the copeptin test. They also said that 1 flaw with the style of the new test is that saline infusions to stimulate copeptin could induce congestive heart failure in high-risk patients.

“These caveats notwithstanding,” Clifford J. Rosen, MD, and Julie R. Ingelfinger, MD, wrote in their editorial, “copeptin measurement after hypertonic saline infusion will probably now replace the water deprivation test to precisely define the cause of polyuria.”

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