Diabetes insipidus (DI) is a condition in which the kidneys are unable to concentrate urine. Central DI, the most common form of diabetes insipidus, is caused by insufficient levels of circulating antidiuretic hormone (ADH); nephrogenic DI, however, is characterized by defective renal ADH receptors. Patients with DI excrete large quantities of diluted urine (polyuria), which causes excessive thirst (polydipsia) in response to fluid loss. Additionally, patients develop the need to urinate at night (nocturia), leading to sleep deprivation and daytime sleepiness. Desmopressin, a synthetic ADH analog, is the treatment of choice in central DI. In nephrogenic DI, hereditary forms are treated with thiazide diuretics or NSAIDs, while acquired forms are first managed by treating the underlying disease.
- Prevalence in the US: 3:100,000 
- Sex: ♀=♂
Epidemiological data refers to the US, unless otherwise specified.
Central diabetes insipidus (CDI)
- Most common form: caused by insufficient or absent hypothalamic synthesis or secretion of antidiuretic hormone (ADH) from the posterior pituitary
Primary (∼ ⅓ of cases)
- Most cases are idiopathic.
- The hereditary form is rare.
- Autoimmune etiology of primary CDI has been suggested 
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)
- Primary (∼ ⅓ of cases)
Nephrogenic diabetes insipidus (NDI)
- Rare: caused by defective ADH receptors in the distal tubules and collecting ducts
- 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)
Urine osmolality changes
- Normal: 500–800 mOsmol/kg
- Partial DI (300–500 mOsmol/kg)
- Complete DI (< 300 mOsmol/kg, often < 100 mOsmol/kg)
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)
- If DI is suspected, sodium, plasma osmolality, and urine osmolality are tested (see expected lab values in the table below).
- A water deprivation test then allows DI to be differentiated from primary polydipsia.
- The patient's response to the administration of desmopressin, furthermore, distinguishes CDI from NDI.
- If CDI is diagnosed, a CT scan or MRI of the head should be conducted to rule out brain tumors (especially craniopharyngioma).
Water deprivation test (confirmatory test) 
- After obtaining baseline lab values, patients stop drinking water for 2–3 hours before the first measurement
- After 2–3 hours without drinking water
- Water deprivation continues until one of the following occurs:
- In the latter two situations → administer desmopressin (a synthetic ADH analog)
|Primary polydipsia vs. central DI vs. nephrogenic DI|
|Primary polydipsia (psychogenic polydipsia)||Central diabetes insipidus||Nephrogenic diabetes insipidus|
|Mechanism|| || || |
Lab findings on presentation
|Sodium|| || |
|ADH levels|| || || |
|Plasma osmolality|| || |
|Urine osmolality|| || |
|Water deprivation test results|
|Desmopressin administration results|
Treat the underlying condition, ensure sufficient fluid intake, and initiate a low-sodium, low-protein diet.
- Central diabetes insipidus
- Nephrogenic diabetes insipidus