Basics
Description
Polyuria and polydipsia caused by the inability to produce or respond to antidiuretic hormone; also called arginine vasopressin
Epidemiology
Incidence
Because most cases are secondary to another disease, the incidence depends on the primary cause.
Risk Factors
Genetics
- Rare genetic causes of central diabetes insipidus (DI) are usually autosomal dominant mutations (neuronal degeneration) and rarely recessive (biologically inactive hormone).
- Nephrogenic DI is usually familial (autosomal recessive or dominant and X-linked).
Pathophysiology
- Antidiuretic hormone stimulates the formation of cyclic adenosine monophosphate (cAMP) in the renal collecting ducts, thereby increasing water permeability and increasing reabsorption of free water.
- Lack of antidiuretic hormone effect results in urinary loss of free water.
- Patients with an intact thirst mechanism drink copiously (polydipsia) to compensate for free water loss.
- If the thirst mechanism is not present or if access to free water is limited (e.g., infants, developmentally delayed child, or vomiting), severe dehydration can occur.
Etiology
- Insufficient antidiuretic hormone secretion
- Traumatic or postsurgical
- Nonaccidental injury
- Related to tumor invasion of posterior pituitary
- Extension from anterior pituitary/suprasellar: optic glioma, rarely adenomas
- Hypothalamic: germinoma, craniopharyngioma, meningioma
- Lymphoma
- Granulomas: histiocytosis, sarcoidosis
- Metastatic carcinoma
- Post-severe ischemic or hypoxic injury to the brain
- Familial (autosomal dominant)
- Congenital malformation of CNS
- Infection: viral encephalitis, meningitis, tuberculosis
- Increased metabolic clearance of antidiuretic hormone (gestational DI)
- Drug or toxin related: snake venom, tetrodotoxin
- Autoimmune disorders: hypophysitis (inflammation of the pituitary gland)
- Psychogenic: excessive water drinking
- Idiopathic: must observe for many years to exclude slow-growing tumors
- Unresponsive to antidiuretic hormone
- Familial or nephrogenic (X-linked dominant and autosomal recessive forms)
- Tumor related
- Urinary tract obstruction, especially in utero
- Renal medullary cystic disease
- Electrolyte disturbances: hypokalemia, hypercalcemia (hypercalciuria)
- Drugs: usually reversible (diuretics, diphenylhydantoin, reserpine, cisplatin, rifampin, lithium [may become permanent], demeclocycline, ethanol, chlorpromazine, volatile anesthetics, foscarnet, amphotericin B)
- Loss of the medullary concentrating gradient due to excessive free water intake relative to solute intake
Alert
Pitfalls
- Management of patients without an intact thirst mechanism and of newborns is difficult.
- Patients with psychogenic polydipsia may fail a water deprivation test because prolonged excessive water intake can wash out the renal medullary gradient required for concentrating the urine.
- Surreptitious water intake during water deprivation test
- Idiopathic, acquired DI can be caused by slowly growing brain tumors not visible on the initial magnetic resonance image.
Diagnosis
History
- Abnormal growth can be a sign of DI.
- Waking up during the night to drink or void:
- True DI is associated with polyuria throughout the day and night. Enuresis may be the first sign in a child who previously acquired bladder control. Patients, including infants, prefer ice-cold water to other liquids.
- Number of hours the patient goes without drinking:
- Patients with complete DI do not voluntarily stop drinking for >1-2 hours unless the thirst mechanism is also abnormal.
- Patients with DI have such overwhelming thirst that they will drink anything, including bath and toilet water.
- Volume of urine output in a day (not just frequency of urination):
- The daily volume of urine can be as high as 4-10 L. Younger or dehydrated children with DI tend to make less urine daily than older or hydrated children with DI.
- Familial history of DI:
- Nephrogenic DI will typically affect maternal uncles during infancy, and mothers may have a mild form.
- Frequent episodes of dehydration requiring medical attention:
- Families may disregard the polydipsia as normal behavior. Repeated episodes of severe dehydration can damage the brain.
- Treatment of adrenal insufficiency in a patient with panhypopituitarism can unmask DI (i.e., one needs cortisol in order to excrete free water).
Physical Exam
- Signs of dehydration:
- DI is typically associated with dry, pale skin and mucous membranes. Because this is hyperosmolar dehydration, the patient may not look as severely dehydrated as she or he is.
- Complete neurologic exam:
- Check for impaired visual fields, which can be the first sign of brain tumor.
Diagnostic Tests & Interpretation
Lab
- Morning urinary osmolality with simultaneous serum sodium and serum osmolality
- If urine osmolality is at least 2 times higher than serum osmolality, patient does not have complete DI but may still have partial DI.
- Water deprivation test
- Although definitive, it requires admission to the hospital for controlled testing under the close supervision of a pediatric endocrinologist. Patient fails test if urinary osmolality cannot concentrate more than twice serum osmolality at the same time that serum osmolality exceeds 305 mOsm/kg; serum osmolality exceeds 305 mOsm/kg at any time; or patient loses >5% of body weight and becomes symptomatic from hypovolemia.
- Once patient fails the water deprivation test, a dose of aqueous vasopressin should be given followed by close monitoring of urinary osmolality to document responsiveness to antidiuretic hormone.
- Never attempt a water deprivation trial at home. Tell parents to allow free access to water at home in any suspected cases.
- Urinary specific gravity (nonspecific)
- Insufficient by itself and nondiagnostic during a water deprivation test
- 24-hour urine collection (home testing)
- To obtain accurate urinary volume while patient has free access to water
Imaging
MRI of the brain with and without contrast, with special cuts of the pituitary and hypothalamus: to confirm the bright spot normally seen in the posterior pituitary and to search for tumors. Its absence is not pathognomonic of central DI.
Alert
Do not restrict water intake unless the patient is in the hospital under close surveillance.
Differential Diagnosis
- Psychogenic polydipsia
- Abnormal thirst mechanism (dipsogenic DI)
- Hypernatremic dehydration
- Diabetes mellitus
- Polyuric renal failure (e.g., renal tubulopathy)
- Hypercalcemia
- Cerebral salt wasting
- Hyperthyroidism
- Hypokalemia
Treatment
Medication
- DDAVP: intranasal spray or oral tablets
- Aqueous vasopressin: subcutaneous (SC):
- Comes as 4 mcg/mL solution and doses range from 0.05 mcg up to 1 mcg SC b.i.d. daily. Titrate dose as you would with DDAVP.
- Duration of action of DDAVP is variable from patient to patient. Titration and frequency of dosing should be made under supervision of a pediatric endocrinologist.
- Control of DI in infants is more difficult. These patients may increase fluid intake because of hunger or increase caloric intake because of thirst, thereby causing an imbalance between free water intake and output. Infants can be treated with diluted formula-the volume and frequency of feedings will be increased, but intake of free water will better match urine output. DDAVP should not be used in infants. In some cases, low renal solute load formula (e.g., Similac PM 60/40) and/or thiazide diuretics have been used in infancy. Strict record keeping of intake/output and accurate daily weighing are usually necessary for infants or patients without an intact thirst mechanism. All infants with DI must be treated by experienced providers.
- Nephrogenic DI may be treated with diuretics and solute restriction as these patients are resistant to DDAVP.
- Side effects:
- Facial flushing
- Increased blood pressure
- Headache
- Nasal congestion
- Hyponatremia: caused by water overdose (intoxication), not by overdose of drug. Taking a higher dose of DDAVP will generally extend the period of antidiuresis but will not cause hyponatremia. Drinking too much water in the setting of antidiuresis causes hyponatremia. Water intoxication most often occurs in antidiuresed patients who also are on intravenous fluids, lack an intact thirst mechanism, or have psychogenic polydipsia.
- Treatment duration is generally lifelong; some tumors regress with radiation, allowing recovery of antidiuretic hormone secretion.
- Possible conflicts with other treatments:
- Nasal congestion or gastrointestinal illness can affect the absorption of DDAVP administered.
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Depends on the patient and underlying disease causing the DI
- When to expect improvement:
- Effects of DDAVP are immediate.
- Most cases of DI are lifelong; one exception is DI that occurs during the 7-10 days immediately after neurosurgery because this postsurgical DI may resolve spontaneously within 1-2 weeks after surgery (part of the triple-phase response).
- Signs to watch for:
- Lethargy
- Somnolence
- Irritability
- Hyperpyrexia
- Any sign of dehydration
- Seizures
Diet
- Patients with an intact thirst mechanism should drink only when thirsty.
- Patients without an intact thirst mechanism should drink only a carefully calculated fluid volume.
Prognosis
- Generally good but depends on the primary cause
- May cause developmental delay if the hypernatremia is prolonged
Complications
- Without treatment and without access to water:
- Hypernatremia
- Dehydration
- Coma
- When overdosed with water:
- Hyponatremia
- Seizures
- Cerebral edema
Additional Reading
- Di Iorgi N, Napoli F, Allegri AE, et al. Diabetes insipidus-diagnosis and management. Horm Res Paediatr. 2012;77(2):69-84. [View Abstract]
- Ghirardello S, Garr ¨ ML, Rossi A, et al. The diagnosis of children with central diabetes insipidus. J Pediatr Endocrinol Metab. 2007;20(3):359-375. [View Abstract]
- Linshaw MA. Back to basics: congenital nephrogenic diabetes insipidus. Pediatr Rev. 2007;28(10):372-380. [View Abstract]
- Maghnie M, Cosi G, Genovese E, et al. Central diabetes insipidus in children and young adults. N Engl J Med. 2000;343(14):998-1007. [View Abstract]
- Rivkees SA, Dunbar N, Wilson TA. The management of central diabetes insipidus in infancy: desmopressin, low renal solute load formula, thiazide diuretics. J Pediatr Endocrinol Metab. 2007;20(4):459-469. [View Abstract]
Codes
ICD09
- 253.5 Diabetes insipidus
- 588.1 Nephrogenic diabetes insipidus
ICD10
- E23.2 Diabetes insipidus
- N25.1 Nephrogenic diabetes insipidus
SNOMED
- 15771004 Diabetes insipidus (disorder)
- 111395007 Nephrogenic diabetes insipidus (disorder)
- 61165007 Hereditary nephrogenic diabetes insipidus
- 81475007 Acquired nephrogenic diabetes insipidus
- 45369008 Neurohypophyseal diabetes insipidus (disorder)
- 237696003 Familial central diabetes insipidus (disorder)
FAQ
- Q: In a patient with an intact thirst mechanism and partial DI, is the use of DDAVP necessary?
- A: No, as long as the patient has constant access to free water.
- Q: How does therapy of DI affect daily life? Is it easily integrated into normal activity and eating patterns?
- A: DDAVP is used in a patient with an intact thirst mechanism to facilitate the daily routine as well as to allow patients to sleep without the need to void frequently during the night.
- Q: Is there a longer acting preparation or an implantable pump for dosing?
- A: The longest acting form of antidiuretic hormone is an injected medication and can have effects for 3 days, increasing the risks of hyponatremia. Home use of the nasal spray or tablets, therefore, is easier and safer than the use of injections.
- Q: In cases of central DI, is it necessary to screen for anterior pituitary hormone deficiencies?
- A: Yes-at diagnosis of DI and during follow-up as other pituitary hormone deficiencies can occur over time.