Polyuria and polydipsia caused by the inability to produce or respond to antidiuretic hormone; also called arginine vasopressin
Because most cases are secondary to another disease, the incidence depends on the primary cause.
- 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).
- 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.
- Insufficient antidiuretic hormone secretion
- Traumatic or postsurgical
- Nonaccidental injury
- Related to tumor invasion of posterior pituitary
- Extension from anterior pituitary/suprasellar region: optic glioma, rarely adenomas
- Hypothalamic: germinoma, craniopharyngioma, meningioma
- 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
- 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.
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