Diabetes Insipidus

Pathophysiology

Diabetes insipidus (DI) is characterized by the inability to concentrate urine due to a dysfunction in the antidiuretic hormone (ADH). This results in the passage of large volumes of dilute urine. The two main subtypes of DI are:

  • Central DI: This occurs when the posterior pituitary gland fails to secrete ADH. Consequently, there is a deficiency of circulating ADH.
  • Nephrogenic DI: In this type, the kidneys are resistant to the effects of ADH, leading to a failure to reabsorb water in the collecting ducts.

Aetiology

The causes of DI vary depending on the subtype.

Central DI:

  • Tumors: Craniopharyngiomas, metastases, pituitary tumors
  • Trauma
  • Ischemia: Sheehan syndrome
  • Pituitary hemorrhage
  • Traumatic brain injury
  • Infections: Meningitis
  • Metastatic disease
  • Autoimmune disorders: Lymphocytic hypophysitis
  • Surgery: Hypophysectomy
  • Infiltration: Histiocytosis, sarcoidosis

Nephrogenic DI:

  • Drug-induced: Lithium, demeclocycline, amphotericin B
  • Metabolic: Hypercalcemia, hypokalemia, hyperglycemia
  • Renal disease: Renal failure with tubular dysfunction, sickle cell nephropathy, post-obstructive uropathy
  • Hereditary: Mutations in the receptor for ADH or in aquaporin 2

Epidemiology/Risk Factors

  • Central DI: Risk factors relate to the underlying causes, such as head trauma, pituitary surgery, or a family history of pituitary disorders.
  • Nephrogenic DI: Lithium use is a significant risk factor, as it can cause nephrogenic DI in a significant proportion of patients. Other risk factors include hypercalcemia, hypokalemia, and chronic kidney disease.

Clinical Features

The hallmark symptom of DI is polyuria (passing large volumes of urine >3 L/day), which is accompanied by polydipsia(excessive thirst). Other clinical features include:

  • Nocturia (frequent urination at night)
  • Enuresis (bedwetting)
  • Volume depletion: This occurs when access to water is restricted and can lead to symptoms such as:
    • Thirst (caused by hypertonicity)
    • Neurologic symptoms including altered mental status, weakness, focal neurologic deficits, and seizures

Investigations

Several investigations are used to diagnose and differentiate between the types of DI.

Laboratory tests:

  • Serum osmolality > urine osmolality: This indicates the kidneys are not concentrating urine appropriately.
  • ↓ Urinary sodium
  • Possible hypernatremia: Elevated serum sodium level due to free water loss

Water deprivation test:

  • Procedure: This test involves depriving the patient of water for a specified period (usually 8 hours) while monitoring their weight, urine output, and urine osmolality.
  • Interpretation:
    • Psychogenic polydipsia and normal renal physiology: Water restriction will lead to more concentrated urine.
    • Central and nephrogenic DI: Patients continue to excrete a high volume of inappropriately dilute urine.

Desmopressin acetate replacement test:

  • Procedure: This test involves administering desmopressin (DDAVP), a synthetic analog of ADH.
  • Interpretation:
    • Central DI: Urine output decreases and urine osmolarity increases by 50–100%.
    • Nephrogenic DI: No significant effect on urine output or urine osmolarity.

Imaging:

  • MRI may show a pituitary or hypothalamic mass in central DI.
  • Ultrasound of kidneys may be helpful in evaluating for causes of nephrogenic DI, such as renal artery stenosis.

Management

The management of DI focuses on treating the underlying cause and managing the symptoms.

Central DI:

  • Desmopressin (DDAVP) replacement: This can be administered intravenously, intranasally, or orally.

Nephrogenic DI:

  • Treat underlying cause
  • Salt restriction
  • Reduced water intake
  • Thiazide diuretics: Such as bendroflumethiazide or hydrochlorothiazide
  • Amiloride
  • NSAIDs: Lower urine volume and plasma sodium by inhibiting prostaglandin synthesis

Complications/Prognosis

Complications of DI:

  • Dehydration: This can lead to electrolyte imbalances (hypernatremia), altered mental status, seizures, and even death if untreated.
  • Growth retardation in children if the condition is not adequately managed.

Prognosis:

  • Central DI: The prognosis depends on the underlying cause. If the cause is treatable, such as a pituitary tumor, the prognosis can be good with appropriate management.
  • Nephrogenic DI: The prognosis can be variable and depends on the severity of the renal resistance to ADH and the underlying cause.