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.
| Etiology (prevalence) | Differentials |
| Neoplastic (50%) | Primary tumors (meningioma, craniopharyngioma, and pinealomas) Secondary tumors (lung or breast metastases) |
| Granulomatous diseases (20%) | Histiocytosis Sarcoidosis |
| Vascular lesions (15%) | Ligation or aneurysm of the anterior communicating artery Hypothalamic hemorrhage Internal carotid artery ligation/dissection |
| Miscellaneous (15%) | Idiopathic, hydrocephalus, ventricular cysts, or brain trauma. |
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)
- Withhold all fluids until body weight decreases by 3-5%, urine osmolality plateaus on 2-3 consecutive assessments, or serum sodium >145mEq/L
- 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
- 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.
- 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.
- 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
| Treament | Examples |
| Water | Required for maintaining hydration status. Ad lib hydration. |
| Water-retaining agents | L-arginine vasopressin, chlorpropramide, carbamazepine, clofibrate, indomethacin, desmopressin. |
| Natriuretic agents | Thiazide diuretics, Amiloride and Indapamide. |
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.
Diagnosis of postoperative central diabetes insipidus
- Urine volume of >250cc per hour for two consecutive hours
- Urine specific gravity <1.005, urine osmolality <200mOsm/Kg H2O.
- Absence of solute diuresis (dipstick negative for glucosuria)
- Serum sodium >145mEq/L
All of the above diagnostic criteria should be met before a diagnosis of postoperative diabetes insipidus can be made.
Initial and subsequent dosing of desmopressin
Administer desmopressin either intravenously or subcutaneously at an initial dose of 1-2mcg. DO NOT administer standing doses of desmopressin until stable due to the possibility of a triphasic response or transient diabetes insipidus. Repeat additional doses of desmopressin when urine output is 200-250cc per hour for at least two hours with either a urine specific gravity of <1.005 or urine osmolality of <200mOsm/kg of H2O.
Desmopressin dose titration and conversion in diabetes insipidus
| Route of administration | Equivalent dose range |
| Parenteral (SC or IV) | 1-2mcg q12h |
| Intranasal | 10-20mcg q8-12h |
| Oral | 100-200mcg (0.1-0.2mg) q6-8h |
Approximately 99% of oral dDAVP is denatured in the gut by peptidases. Oral dDAVP should be administered either 1 hour before or 2 hours after meals.
Maintenance of fluid balance
Patients should be permitted to drink according to their thirst. If patients are unable to keep up with fluid intake, supplement fluid requirements with hypotonic intravenous fluids. Start with 5% Dextrose in water (D5W) followed by 5% Dextrose in 0.45% (half-normal) saline.
Monitoring for transient or triphasic response of diabetes insipidus
A positive daily fluid balance exceeding 2L suggests inappropriate anti-diuresis. dDAVP should be suspended and fluids restricted to maintain serum sodium and osmolality within the normal reference range.
Management of possible anterior pituitary hormonal insufficiency
Patients should receive stress dose glucocorticoids – IV hydrocortisone 100mg every 8 hours. This should be tapered and converted to oral hydrocortisone 15-30mg daily until full anterior pituitary function can be assessed at a later date.
Clinical Pearl
- Serum hypoosmolarity in the setting of polyuria almost always clinches the diagnosis of primary polydipsia
- Serum hyperosmolarity in the setting of polyuria clinches the diagnosis of neurogenic/central diabetes insipidus
References
- Loh JA, Verbalis JG. Diabetes insipidus as a complication after pituitary surgery. Nat Clin Pract Endocrinol Metab. 2007 Jun;3(6):489-94.
- Verbalis JG. Acquired forms of central diabetes insipidus: Mechanisms of disease. Best Pract Res Clin Endocrinol Metab. 2020 Sep;34(5):101449.
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