Diabetes insipidus (DI) is a condition in which the kidneys cannot effectively concentrate urine, resulting in hypotonic polyuria. Central DI (CDI), the most common form of DI, is caused by decreased hypothalamic production or pituitary release of antidiuretic hormone (ADH), resulting in insufficient levels of circulating ADH. CDI can be primary (idiopathic) or secondary to brain lesions or injury. Nephrogenic DI (NDI) is characterized by ADH resistance and may be hereditary or acquired. Patients with DI typically develop polydipsia in response to excessive fluid loss. Most patients also experience nocturia, which can lead to sleep deprivation and daytime sleepiness. DI is initially diagnosed based on the presence of hypotonic polyuria on a 24-hour urine collection. Subsequently, confirmatory testing (e.g., water deprivation test) can differentiate between CDI, NDI, and primary polydipsia. Patients with DI should be encouraged to compensate for urinary fluid losses with oral fluids. For CDI, pharmacotherapy with desmopressin (a synthetic ADH analogue) may be used. For acquired NDI, management involves treating the underlying cause (e.g., correcting metabolic derangement, relieving obstructive uropathy, or discontinuing the causative drug); the condition is typically reversible within weeks to months, although lithium-induced NDI may be irreversible. In some cases, pharmacotherapy with thiazide diuretics, NSAIDs, or amiloride may be indicated.
- Prevalence in the US: 3:100,000 
- Sex: ♀=♂
Epidemiological data refers to the US, unless otherwise specified.
- Most common form: caused by insufficient or absent hypothalamic synthesis or posterior pituitary secretion of ADH
- Primary (∼ ⅓ of cases)
Secondary (∼ ⅔ of cases)
- Brain tumors (especially craniopharyngioma) and cerebral metastasis (most common: lung cancer and leukemia/lymphoma)
- Neurosurgery: usually after the removal of large adenomas
- Traumatic brain injury, pituitary bleeding, subarachnoid hemorrhage
- Pituitary ischemia (e.g., , ischemic stroke)
- Infection (e.g., meningitis)
- Subtype: adipsic diabetes insipidus
DI following neurosurgery (e.g., transsphenoidal surgery) is usually transient.
- Rare: caused by defective ADH receptors in the distal tubules and collecting ducts
- Hereditary (mutation in ADH receptor): very rare
- Acquired: typically reversible if the underlying cause is resolved
- ADH enables the integration of aquaporins into the plasma membrane of collecting duct cells → reabsorption of free water
- Either ↓ ADH (central DI) or defective renal ADH receptors (nephrogenic DI) → impaired ability of the kidneys to concentrate urine (hypotonic collecting ducts) → dilute urine (low urine osmolarity)
Hyperosmotic volume contraction 
- Loss of fluid with urine → increased extracellular fluid osmolarity → passage of fluid from the intracellular to the extracellular space → equalization of the osmolarities of the extracellular and intracellular fluid
- Due to the loss of fluid, the osmolarities of intracellular and extracellular compartments are now higher (hyperosmotic) than the initial values.
- The fluid volume is redistributed between the two compartments to equalize the osmolarities and remains lower than the initial values in each of them (volume contraction)
- Polyuria with dilute urine
- Nocturia → restless sleep, daytime sleepiness
- Polydipsia (excessive thirst)
- In cases of low water intake → severe dehydration (altered mental status, lethargy, seizures, coma) and hypotension
- Symptoms may worsen during pregnancy.
- Obtain a thorough patient history and perform a physical examination to assess for possible .
- Obtain initial studies including serum sodium, plasma osmolality, and urine osmolality.
- Obtain subsequent studies (e.g., water deprivation test) to distinguish between primary polydipsia, CDI, and NDI.
- See also “Differential diagnosis of polyuria-polydipsia syndromes” for expected laboratory findings.
- Obtain imaging to rule out brain tumors in patients with CDI.
Initial laboratory studies 
- Routine studies: BMP, urinalysis
- 24-hour urine collection: to confirm hypotonic polyuria, i.e., urine volume > 50 mL/kg/24 hours with urine osmolality < 800 mOsm/kg
Serum sodium and plasma osmolality
- ↓ Na+ and/or ↓ plasma osmolality: primary polydipsia likely
- Normal values: diagnosis unclear; obtain subsequent studies to differentiate between polyuria-polydipsia syndromes.
- ↑ Na+ and/ or ↑ plasma osmolality: Diabetes insipidus likely; obtain subsequent studies to differentiate between CDI and NDI.
Subsequent laboratory studies 
- To distinguish between polyuria-polydipsia syndromes, ADH activity can be assessed directly or indirectly.
- Consult endocrinology for guidance and follow local testing protocols if available.
Water deprivation test (indirect assessment of ADH activity)
- Interpretation after period of water deprivation
Interpretation after desmopressin administration
- Urine osmolality (300–800 mOsm/kg) and:
- Urine osmolality (< 300 mOsm/kg) and:
- Circulating plasma copeptin levels reflect circulating ADH levels.
- Measure random plasma copeptin levels.
Brain imaging 
- Indications: suspected or confirmed CDI to determine the underlying cause
- Preferred modality: pituitary or sella protocol MRI
- Supportive findings: may reveal a tumor, inflammation, or infiltrative changes in the posterior pituitary gland
Differential diagnosis of polyuria-polydipsia syndromes
See also “Gestational diabetes insipidus.”
|Primary polydipsia vs. central DI vs. nephrogenic DI |
|Central diabetes insipidus||Nephrogenic diabetes insipidus||Primary polydipsia (psychogenic polydipsia)|
|Mechanism|| || |
|ADH|| || || |
|Initial studies||Serum sodium|| |
|Plasma osmolality|| || |
|Urine osmolality|| || |
Indirect assessment of ADH activity
|Water deprivation test|| |
|After desmopressin administration|| |
Other causes of polyuria and/or polydipsia
- Other causes of
- Beer potomania: dilutional hyponatremia secondary to limited renal free water excretion caused by intake of large amounts of beer 
The differential diagnoses listed here are not exhaustive.
General principles 
- Encourage adequate fluid intake and a low-sodium, low-protein diet.
- Initiate (i.e., ) as needed.
- Treat according to the underlying mechanism and cause.
Hypernatremia is rare in the ambulatory setting but may be present in patients with cognitive impairment, , and those who are hospitalized or cannot access water because of mobility impairment. 
- Management should be guided by an endocrinologist.
- Most patients are able to maintain eunatremia through increased oral fluid intake alone.
- Initiate pharmacotherapy in patients with either:
Desmopressin (preferred): synthetic ADH analogue without vasoconstrictive effects
- Intranasal administration is preferred.
- Typically at bedtime to relieve nocturia
- Start at a low dose to reduce the risk of overcorrection.
- Chlorpropamide (alternative): enhances the effect of ADH and increases its secretion
- Desmopressin (preferred): synthetic ADH analogue without vasoconstrictive effects
Most patients with CDI are able to increase their oral fluid intake to maintain eunatremia without pharmacotherapy. However, desmopressin is typically required to relieve bothersome symptoms of polyuria and polydipsia. 
- Consult nephrology as needed for guidance on management.
- Treat the underlying cause, if applicable, e.g.:
- Consider pharmacotherapy to manage polyuria and hypernatremia.
- Thiazide diuretics
- NSAIDs (e.g., indomethacin)
- Amiloride: indicated in patients with lithium-induced NDI who continue lithium therapy
Special patient groups
Gestational diabetes insipidus 
- Definition: transient diabetes insipidus caused by increased activity and/or circulating levels of vasopressinase during pregnancy that typically resolves after delivery
- Etiology: decreased metabolization of vasopressinase due to impairment in hepatic function (e.g., HELLP, AFLP, hemochromatosis)
- Clinical features: same as in non-pregnant individuals
- Treatment: desmopressin
- Complications: preeclampsia, oligohydramnios