• Clinical science

Diabetes insipidus

Abstract

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.

Epidemiology

References:[1]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[1][2][3][4][5][6][7][8][9]

Pathophysiology

  • 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)

References:[1][10]

Clinical features

  • Polyuria with dilute urine
  • Nocturia → Restless sleep, daytime sleepiness
  • Polydipsia
  • In cases of low water intake → severe dehydration (altered mental status, lethargy, seizures, coma) and hypotension

In the absence of nocturia, diabetes insipidus is very unlikely!
References:[9][11]

Diagnostics

Approach

  • 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).

Water deprivation test (confirmatory test)

  • 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:
    • Urine osmolality rises and reaches a normal value (> 600 mOsmol/kg) → DI ruled out and primary polydipsia confirmed
    • No change in urine osmolality despite a rising plasma osmolality (> 290 mOsmol/kg)
    • Plasma osmolality > 295–300 mOsmol/kg or sodium ≥ 145 meq/L
  • In the latter two situations → administer desmopressin (a synthetic ADH analog)
Primary polydipsia (psychogenic polydipsia ) CDI NDI

Lab findings on presentation

  • Hyponatremia (< 137 meq/L)
  • Plasma osmolality: low-normal (255–280 mOsmol/kg)
  • Very low urine osmolality (< 250 mOsmol/kg)
  • Mild hypernatremia (> 150 mEq/L)
  • High-normal plasma osmolality (280–290 mOsmol/kg) or slightly elevated
  • Low urine osmolality
    • Partial DI: 300–500 mOsmol/kg
    • Complete DI: < 300 mOsmol/kg
Water deprivation test results
  • Plasma osmolality: normal (275–290 mOsmol/kg)
  • Urine osmolality: rises, reaches normal value (> 600 mOsmol/kg) This result shows that both ADH release and effect are intact.
  • Plasma osmolality: rises (> 290 mOsmol/kg)
  • Urine osmolality: no change
Desmopressin administration results
  • Plasma osmolality: normalizes (275–290 mOsmol/kg)
  • Urine osmolality rises:
    • In partial CDI: ∼ 10%
    • In complete CDI: by > 50%
  • Plasma osmolality remains elevated
  • Urine osmolality remains low:
    • In partial NDI: ∼10%
    • In complete NDI: no change

References:[1][10][12][13]

Differential diagnoses

References:[14]

The differential diagnoses listed here are not exhaustive.

Treatment

References:[15][16][17][18][19][20]