How is diabetes insipidus (DI) diagnosed?

Updated: Mar 18, 2020
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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A urinary specific gravity of 1.005 or less and a urinary osmolality of less than 200 mOsm/kg are the hallmark of DI. Random plasma osmolality generally is greater than 287 mOsm/kg. Suspect primary polydipsia when large volumes of very dilute urine occur with plasma osmolality in the low-normal range. Polyuria and elevated plasma osmolality despite a relatively high basal level of ADH suggests nephrogenic DI.

Water deprivation followed by the administration of vasopressin may help to differentiate central from nephrogenic DI. The result of this test must be interpreted with caution, however, because patients with partial nephrogenic DI or primary polydipsia may show a response similar to that seen in central DI.

A prospective study by Winzeler et al indicated that measurement of plasma copeptin at baseline and following arginine stimulation may be an effective means of differentiating DI from primary polydipsia. In healthy adults and patients with primary polydipsia, arginine stimulation resulted in a rise in copeptin concentrations from 5.2 pM and 3.6 pM, respectively, to a maximum of 9.8 pM and 7.9 pM, respectively. In patients with DI (in this study, central DI), however, the concentration rose from 2.1 pM to a maximum of only 2.5 pM. Using a cutoff of 3.8 pM of copeptin at 60 minutes, the stimulation test reached optimal accuracy, at 93%, with a sensitivity of 93% and a specificity of 92%. [29]

Historically, diagnostic tests in DI can be traced back to the 1930s, when Gilman and Goodman first demonstrated recovery of an antidiuretic substance in the urine of rats following dehydration with hypertonic saline. When animals were provided free access to water, no antidiuretic activity was recovered from urine, and no antidiuretic activity could be recovered from the urine of hypophysectomized rats dehydrated with hypertonic saline. [30]

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