There are numerous challenges associated with identifying the underlying cause of polyuria. Among several possibilities, a diagnosis of diabetes insipidus (DI) must be considered. This condition affects an estimated 20% of patients after transsphenoidal surgery, typically within 24 to 48 hours, as a result of impaired hypothalamic-neurohypophyseal neuronal connections. DI also occurs in 20% of those with traumatic brain injury during the acute phase and in 15% of patients with subarachnoid hemorrhage.1

These cases are typically transient, with persistent DI occurring rarely. In addition, although 50% of DI cases were previously believed to be idiopathic, several studies point to autoimmune mechanisms, including research published in 2003 demonstrating that more than one-third of patients with idiopathic DI had positive vasopressin (AVP) cell antibodies.1,2

In patients with hypotonic polyuria, the first diagnostic task is to distinguish among 3 primary etiologies: insufficient arginine AVP secretion (central DI), impaired renal sensitivity to AVP (nephrogenic DI), and excessive thirst/fluid intake (primary polydipsia).1 It is critical to identify the underlying cause accurately, as misdiagnosis can lead to inappropriate treatment and severe complications.

Currently, the gold standard test for DI diagnosis is the indirect water deprivation test. “However, it is technically cumbersome to administer, and the results are often inaccurate,” wrote the investigators of a study published in August 2018 in the New England Journal of Medicine.3 These issues highlight the need for a simplified, more accurate diagnostic test for DI. To that end, the researchers investigated the direct testing of plasma copeptin — an “arginine vasopressin surrogate with high ex vivo stability that is easy to measure” — as an alternative to the water deprivation test. In previous research, copeptin has shown promise in distinguishing between the causes of hypotonic polyuria.4-6

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In the 2018 study, investigators examined the diagnostic accuracy of the water deprivation test compared with the accuracy of measuring hypertonic saline-stimulated copeptin in patients with hypotonic polyuria.3 The final sample for analysis included 141 participants who underwent both tests and were recruited from 11 medical centers in several countries. For the copeptin test, plasma copeptin was measured when the plasma sodium level had increased to ≥150 mmol/L after infusion of hypertonic saline.

Study results showed that an accurate diagnosis was identified with the water deprivation test in 76.6% of patients (95% CI, 68.9-83.2) vs 96.5% with the hypertonic saline infusion test (95% CI, 92.1-98.6; P <.001), using a copeptin cutoff level of >4.9 pmol/L.3

In distinguishing between primary polydipsia and partial central DI, the water deprivation test had an accurate result in 73.3% of cases (95% CI, 63.9-81.2) compared with 95.2% of cases with the hypertonic saline infusion test (95% CI, 89.4-98.1; adjusted P <.001).3

Only 1 serious adverse event was observed: desmopressin-induced hyponatremia resulting in hospitalization occurred in a patient undergoing the water deprivation test.3