Diabetes Insipidus Workup

Pituitary hormone testing

In a study of 89 patients with traumatic brain injury (TBI), 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).^[9]

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 magnetic resonance imaging (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.^[9]

Magnetic resonance imaging

On pituitary MRI, T1-weighted images of the healthy posterior pituitary yield a hyperintense signal. In patients with central diabetes insipidus, this signal is absent, except in the rare familial form of central diabetes insipidus.^[10]

The diagnosis of diabetes insipidus (DI) is often made clinically, while the laboratory tests provide confirmation. Perform testing with the patient maximally dehydrated as tolerated—that is, at a time when antidiuretic hormone (ADH) release would be highest and urine would be most concentrated. Ruling out secondary causes, such as diabetes mellitus, is also important.

The clinician should measure serum electrolytes and glucose, urine specific gravity, urinary sodium, simultaneous serum and urine osmolality, and ADH levels. A urine specific gravity of 1.005 or less and a urine osmolality less than 200 mOsm/kg are the hallmark of diabetes insipidus. Random plasma osmolality generally is greater than 287 mOsm/kg.

The water deprivation test (ie, the Miller-Moses test), a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis, is performed in ambiguous clinical circumstances, typically with more chronic forms of diabetes insipidus (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 urine osmolality and body weight are measured hourly. When 2 sequential urine osmolalities vary by less than 30 mOsm/kg or when the weight decreases by more than 3%, 5 U of aqueous ADH is administered subcutaneously. A final urine specimen is obtained 60 minutes later for osmolality measurement.

In healthy individuals, water deprivation leads to a urine osmolality that is 2-4 times greater than plasma osmolality. Administration of ADH results in less than 9% increment in urine osmolality. The time required to achieve maximal urine concentration ranges from 4-18 hours.

In complete central DI, testing reveals minimal ADH levels and activity, and the urine does not become concentrated despite excessively concentrated serum. In response to exogenous ADH, urine osmolality increases by more than 50%.

Patients with nephrogenic DI have a normal to elevated serum ADH level, and their kidneys fail to respond to exogenous ADH during the water deprivation test.