Diabetes Insipidus

Basics

Description

Polyuria and polydipsia caused by the inability to produce or respond to antidiuretic hormone; also called arginine vasopressin

Epidemiology

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 region: 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.

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