Description

• A condition in which there is reduced ability to concentrate the urine due to impaired reabsorption of water in the renal collecting tubules
• It is characterized by polyuria and, in sensate patients, pronounced thirst.
• Two main forms of diabetes insipidus (DI) are known. Central diabetes insipidus (CDI) represents vasopressin (antidiuretic hormone [ADH]) deficiency. Nephrogenic diabetes insipidus (NDI) represents target end organ (renal tubule) unresponsiveness to vasopressin/ADH. Rarely, DI can be induced by pregnancy, known as gestational diabetes insipidus (GDI).
• System(s) affected: endocrine/metabolic/renal

Epidemiology

Incidence

• DI occurs in 3/100,000 persons in the general population.
• Vasopressin deficiency (CDI) may occur at any age and has no gender preference.
• NDI in children is most often congenital and usually manifests during infancy.
• The most common causes of acquired NDI are long-term lithium therapy and chronic hypercalcemia.
• Pediatric NDI is encountered in males more commonly, reflecting its X-linked recessive mode of inheritance.

Prevalence

• CDI: 1 in 25,000 persons
• NDI: unknown
• GDI: 2 to 6 in 100,000 pregnancies (1)

Etiology and Pathophysiology

• CDI
  • Inadequate secretion of vasopressin may be due to loss or malfunction of the neurosecretory cells of the neurohypophysis (posterior pituitary) and the pituitary stalk.
  • Posterior pituitary lesions rarely cause CDI because ADH is produced in the hypothalamus and therefore, still may be secreted above the level of injury.
  • Collecting tubule fails to reabsorb water effectively from filtrate due to ADH deficiency or absence.
  • Can be complete or partial
  • Etiology:
    • Trauma/head injury: A study of 89 patients with traumatic brain injury found that primary hormonal dysfunction (including DI) occurred in 21% of patients and tended to occur in patients with the lowest Glasgow Outcome Scale scores (2).
    • Neurosurgery: A study of 102 consecutive craniopharyngioma surgeries found that postoperative DI is more common in children than adults (80% vs. 63%), with higher incidence of permanent DI in children (55.6%) (3).
    • Tumors (e.g., craniopharyngioma, lymphoma, metastasis)
    • Infections (e.g., meningitis, encephalitis)
    • Infiltrative diseases (e.g., sarcoidosis, histiocytosis)
    • Hypoxic encephalopathy
    • Vascular disorders
    • Congenital: Brain dysmorphisms may be identified in up to a quarter of children with CDI (4) but recognizable heritable defects only in 1–2%.
• NDI
  • Target organ (renal) unresponsiveness to vasopressin
  • Reabsorption of water from filtrate in collecting tubules is impaired despite presence of ADH.
  • Can be complete or partial
  • Etiology:
    • Drug-induced (amphotericin B, colchicine, demeclocycline, foscarnet and other antivirals, aminoglycosides, lithium carbonate, loop diuretics, methoxyflurane). Inappropriate or excessive use of vasopressin antagonists such as tolvaptan mimics NDI.
    • Heritable defects, including X-linked V₂ receptor gene mutation and autosomal recessive aquaporin-2 gene mutation
    • Electrolyte disorders, especially hypercalcemia and hypokalemia
    • Renal tubular disorders
    • Partial ureteral obstruction and postobstructive state
• GDI
  • Placentally-produced vasopressinase shortens half-life of vasopressin in circulation (1).
  • It is usually a transient condition but is commonly undiagnosed (1).

Risk Factors

• Intracranial neoplasm
• Infection
• Intracranial surgery (especially pituitary)
• Medications (amphotericin B, colchicine, demeclocycline, antiviral agents, aminoglycosides, lithium, loop diuretics, methoxyflurane)
• Head trauma
• Genetic predisposition

Commonly Associated Conditions

• NDI
  • Potassium depletion
  • Chronic hypercalcemia
  • Renal amyloidosis
  • Tubulointerstitial nephritides
  • Sjögren syndrome
  • Sickle cell anemia
  • Multiple myeloma
  • Developmental delay (in congenital NDI)
• CDI
  • Tumors (primary and metastatic)
  • Infections (encephalitis, TB, syphilis)
  • Xanthomatosis
  • Sarcoidosis
  • Histiocytoses
  • Wolfram syndrome (DIDMOAD: DI, diabetes mellitus, optic atrophy, deafness)