Diabetes Insipidus Workup

Updated: Feb 21, 2018
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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Workup

Approach Considerations

In a patient whose clinical presentation suggests diabetes insipidus (DI), laboratory tests must be performed to confirm the diagnosis. A 24-hour urine collection for determination of urine volume is required. In addition, the clinician should measure the following:

  • Serum electrolytes and glucose

  • Urinary specific gravity

  • Simultaneous plasma and urinary osmolality

  • Plasma antidiuretic hormone (ADH) level

Perform testing with the patient maximally dehydrated as tolerated—that is, at a time when ADH release is the highest and his/her urine is the most concentrated. Water deprivation testing may be useful in situations in which the diagnosis is uncertain.

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.

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. [25]

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Water Deprivation Testing

The water deprivation test (ie, the Miller-Moses test), a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis, is typically performed in patients with more chronic forms of DI. The extent of deprivation is usually limited by the patient’s thirst or by any significant drop in blood pressure or related clinical manifestation of dehydration.

With mild polyuria, water deprivation can begin the night before the test. With severe polyuria, water restriction is carried out during the day to allow close observation.

All water intake is withheld, and urinary osmolality and body weight are measured hourly. When 2 sequential urinary osmolalities vary by less than 30 mOsm/kg or when the weight decreases by more than 3%, 5 U of aqueous ADH or desmopressin are administered subcutaneously. A final urine specimen is obtained 60 minutes later for osmolality measurement.

In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma osmolality. Additionally, in normal, healthy subjects, administration of ADH produces an increase of less than 9% in urinary osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.

In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation. After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at all in nephrogenic DI. In primary polydipsia, urinary osmolality be above 750 mOsm/kg after water deprivation. A urinary osmolality that is 300-750 mOsm/kg after water deprivation and remains below 750 mOsm/kg after administration of ADH may be seen in partial central DI, partial nephrogenic DI, and primary polydipsia. [26]

Water deprivation test results may be misleading in patient with chronic primary polydipsia, who may experience partial washout of the medullary interstitial gradient and downregulation of ADH release. This would resemble nephrogenic DI, with an inability to concentrate urine. The combination of a plasma ADH assay with water deprivation testing can lead to greater accuracy in differentiating the different forms of DI from each other and from primary polydipsia. [27]

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Pituitary Studies

On MRI, T1-weighted images of the healthy posterior pituitary yield a hyperintense signal. This signal is also invariably present in primary polydipsia. In patients with central DI, this signal is absent, except in a few children with the rare, familial form of the disorder. [28] It is also absent in most patients with nephrogenic DI.

Measurement of circulating pituitary hormones other than ADH may be valuable after traumatic brain injury (TBI). In a study of 89 TBI patients, in which the patients’ hormonal function was evaluated at the time of injury and afterward (at 3, 6, and 12 months), Krahulik et al found primary hormonal dysfunction—including major deficits such as DI, growth hormone dysfunction, and hypogonadism—in 19 patients (21% of the cohort). [29]

The major deficits tended to occur in patients with the worst Glasgow Outcome Scale scores. Moreover, the occurrence of empty sella syndrome, as revealed on MRI scans, was highest in patients with deficits. The authors recommended that pituitary hormone testing be routinely performed within 6 months and 1 year after injury in patients who have sustained a moderate to severe TBI. [29]

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Imaging Studies

A study by Wang et al indicated that the extent of deformation of the third ventricle and hypothalamus, as evaluated through preoperative magnetic resonance imaging (MRI), may help to predict the occurrence of DI subsequent to transcranial surgery for pituitary adenoma. The investigators found a positive correlation between the degree of deformation of the third ventricle and hypothalamus and the development of immediate postoperative DI, with postoperative hemorrhage also being linked to a higher degree of deformation. Moreover, postoperative hemorrhage was found to be associated with permanent DI. [30]

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