Diabetes insipidus

Patients with diabetes insipidus present with hypotonic polyuria and polydipsia. There are two forms of diabetes insipidus – central and nephrogenic.

Causes of Central Diabetes Insipidus

Central (neurogenic) diabetes insipidus is rare, with a prevalence of 1:25,000. A hypothalamic lesion is present in up to 50% of patients. Pituitary adenomas are generally not large enough cause diabetes insipidus.

Diagnostic criteria of Diabetes Insipidus

Diagnostic criteria

• 24-hour urine volume >50ml/kg under conditions of ad-lib intake
• Urine specific gravity <1.010, Urine Osm <300mOsm/kg H2O
• Absence of solute diuresis (dipstick negative for glucose)

All three diagnostic criteria should be fulfilled before a formal water deprivation test. Indeed,  failure to meet any of these criteria (24hr urine) renders further evaluation unnecessary

Water deprivation test

The procedure of a formal water deprivation test. An overnight outpatient water deprivation test can be attempted safely in most cases prior to proceeding with a more laborious inpatient (formal) water deprivation test. Outpatient testing involves withholding all fluids after dinner until the following morning.

Serum sodium and spot urine osmolality should be assessed in the morning. If the urine osmolality is >800 mOsm per Kg of H20 (indeed >600 in most cases), diabetes insipidus is highly unlikely. As such, a formal water deprivation test will not be needed.

Water Deprivation Test

Formal (inpatient testing)

1. Withhold all fluids until body weight decreases by 3-5%, urine osmolality plateaus on 2-3 consecutive assessments, or serum sodium >145mEq/L
2. If any of the above criteria are met, administer 1 mcg of dDAVP subcutaneously and assess urine osmolality and volume in 2 hours.

Interpretation of the water deprivation test result

• If urine osmolality increases >50% after dDAVP administration, this suggests a diagnosis of central diabetes insipidus.
• If urine osmolality increases <10% after dDAVP administration, this suggests a diagnosis of nephrogenic diabetes insipidus.
• If urine osmolality increases between 10-50% (intermediate response) after dDAVP administration, this suggests an equivocal test (additional testing required)

Combined water deprivation test

1. Withhold ALL fluids until the patient’s body weight decreases by 3-5%, urine osmolality plateaus on 2-3 consecutive assessments or serum sodium >145mEq/L. If serum sodium is not >145mEq/L at the end, infuse 3% of NaCL (0.1ml/kg/min) for 1 to 2 hours until serum sodium is >145mEq/L.
2. Draw plasma AVP level, plasma osmolality, and urine osmolality both at the beginning and conclusion of the test, then administer 1mcg of dDAVP subcutaneously. Subsequently, measure urine osmolality and volume for 2 more hours.
3. Compare baseline and post-water deprivation AVP levels in relation to plasma and urine osmolalities in order to distinguish between central and nephrogenic diabetes insipidus.

Treatment of diabetes insipidus

 Desmopressin (dDAVP) is a synthetic analog of vasopressin in which the substitution of D-arginine markedly reduces vasopressor activity, and removing the terminal amine increases the half-life of an agent nearly 2000 times more specific for antidiuresis than the naturally occurring L-arginine vasopressin

• Desmopressin is administered, and the patient is permitted to drink fluid ad lib. A reduction in urine volume is typically noted within 1 to 2 hours. The estimated duration of action is usually 6 to 18 hours.
• Of note, an optimal treatment schedule can be achieved with a modest dose of2 mg of dDVAP orally (3 times a day) or 20 μg intranasally (two sprays, twice daily)

Management of postoperative diabetes insipidus

Patients undergoing transsphenoidal surgery for pituitary adenomas are at risk of developing diabetes insipidus. Expectant monitoring involves accurately recording fluid intake and output in the perioperative period. Significant polyuria in the postoperative period may be transient or suggestive of central diabetes insipidus. Urine osmolality, urine specific gravity, and serum sodium should be monitored every 4-6hours until the resolution of polyuria.