- Clinical science
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 in the kidneys. 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.
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., )
- 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
- Complete DI (< 300 mOsmol/kg, often < 100 mOsmol/kg)
- Partial DI (300–500 mOsmol/kg)
- If DI is suspected, sodium, plasma osmolality, and urine osmolality values 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).
- After obtaining baseline lab values, patients stop drinking water for 2–3 hours before the first measurement
- After 2–3 hours without drinking water
- Test urine volume and osmolality every hour
- Test sodium and plasma osmolality every two hours
- Water deprivation continues until one of the following occurs:
- In the latter two situations → administer desmopressin (a synthetic ADH analog)
|Primary polydipsia (psychogenic polydipsia )||CDI||NDI|
Lab findings on presentation
|Water deprivation test results|| |
|Desmopressin administration results|| || |
The differential diagnoses listed here are not exhaustive.
- Treat the underlying condition and initiate a low-sodium, low-protein diet
- Central diabetes insipidus
- Nephrogenic diabetes insipidus