Diabetes Insipidus

Pathological absence of or insensitivity to ADH which impairs renal concentrating ability, leading to:

• Polyuria
  Obligatory solute load is cleared in a very dilute urine.
• Polydipsia
  If awake, and able to maintain free water intake.
• Hypovolaemia and hyperosmolarity
  If unable to meet free-water requirements.

DI is subdivided into:

• Nephrogenic DI
  Insensitivity of the kidney to circulating ADH.
• Neurogenic (central) DI
  Complete or partial loss of ADH production.
• Gestational DI
  Various mechanisms, including:
  • ↑ Placental vasopressinase production
    May be the sole cause, or unmask a previous relative ADH deficiency.
  • Pre-eclampsia
  • HELLP syndrome

Epidemiology and Risk Factors

Pathophysiology

Under normal circumstances:

• The daily obligatory solute loss is ~800mmol
  300mmol of urea and 500mmol of assorted ions.
• The kidney can produce urine:
  • As dilute as 25mOsmol/kg
    
  • As concentrated as ~1200mOsmol/kg

Excretion of the ordinary daily solute load therefore requires:

• ~666mL, assuming a maximally-concentrated urine
• ~32L, assuming a maximally-dilute urine

• Variations in urine output occur due to changes in free water intake
• Diuresis describes urine output >1.5mL/kg/hr, and can be:
  • Water diuresis
    Normal solute excretion with low urine osmolality.
  • Solute diuresis
    Higher solute excretion with variable urine osmolality:
    • Iso-osmolar if hypervolaemic
    • Hyperosmolar if hypo- or euvolaemic
      
      
• Volume and plasma osmolality are regulated by different mechanisms and so can occur independently
  • The RAAS is the prime determinant of volume state
  • ADH is the prime determinant of osmolality
    • Secreted in response to ↓ plasma osmolality
    • V₂ receptors in the kidney:

Partial or complete absence of ADH leads to:

• Impaired water reabsorption
• Production of a large volume of dilute urine
  • In an awake patient with intact thirst mechanisms, this is matched with a high volume of free water intake
  • Otherwise, results in hypovolaemia and hyper-osmolar serum

In pregnancy, there is a:

• ↓ In normal plasma osmolality (to 265-285mOsmol/kg) and sodium (130-145mmol/L)
• ↑ In ADH secretion
• ↑ In aldosterone production
• ↑ GFR and solute load

Aetiology

Neurogenic DI:

Neurogenic DI may be complete or partial, depending on the severity of the lesion.

• Vascular
  • Strokes
  • Sheehan’s syndrome
  • Aneurysm
• Inflammatory
  • Sarcoidosis
  • Sickle-cell disease
  • Encephalitis
  • Wegener’s granulomatosis
• Neoplasm
  • Primary tumour
    Suprasellar.
  • Metastatic disease
• Drugs
  • Amiodarone
  • Lithium
    May also cause nephrogenic DI.
• Idiopathic
• Congenital
  • Congenital cranial DI
    Autosomal dominant loss of ADH producing cells that reveals itself between 1 and middle age.
• Autoimmune
• Trauma
  • Hypoxic brain injury
  • Surgery

Nephrogenic DI:

• Renal
  • Post-obstructive diuresis
  • Polycystic kidney disease
  • Pyelonephritis
  • Transplant
• Electrolyte
  • Hypercalcaemia
  • Hypokalaemia
  • Hypoproteinaemia
• Drugs
  • Lithium
    >20% of patients on chronic lithium therapy.
  • Amiodarone
  • Frusemide
  • Gentamicin
  • Amphotericin B

Clinical Manifestations

Diagnostic Approach and DDx

Investigations

Bedside:

Laboratory:

• Blood
  • UEC
  • Osmolality
    Measured osmolality may be high.
  • ↑ Na⁺
  • TFT
  • Prolactin
• Urinalysis
  Paired with serum.
  • Sodium
  • Osmoles

With complete absence of ADH, >20L/day of very dilute (25-200mOsmol/kg) of urine can be produced.

Partial absence of ADH may lead to ~3L/day of moderately dilute (500-800mOsmol/kg) urine.

Imaging:

• MRI
  Investigation of hypothalamic or pituitary injury and likelihood of recovery.

Hypothalamic lesions are less likely to recover than pituitary injuries.

Other:

• Water deprivation test

Management

• Correction of hypernatraemia
• Correction of volume state
• Correction of underlying ADH deficiency
• Investigation of other anterior pituitary hormone deficiencies

Neurogenic Diabetes Insipidus

Specific therapy:

Free water deficit can be crudely estimated as: \(Free \ Water \ Deficit = 0.6 \times Weight \times (1 - {Na_{ideal} \over Na_{serum}})\)

Where:

• Free water deficit is in litres
• Weight is in kg
• Serum sodium is in mmol/L

• Pharmacological
  • Sodium correction
    Hypernatraemia >48 hours duration should be corrected at <10mmol/L/day.
  • Volume correction
    • 0.9% Saline is preferable
    • Careful titration is required in hypernatraemia to avoid a rapid correction
      • Consider hypertonic saline to ↓ rate
  • Exogenous ADH
    Indicated if euvolaemic and UO >3mL/kg/hr.
    • DDAVP 1-4μg IV daily
      Adjusted to control of UO.
  • Consider corticosteroids
    Indicated if clinical concern about adrenal insufficiency due to anterior pituitary disruption.
    • 100mg hydrocortisone

Nephrogenic Diabetes Insipidus

Specific therapy:

• Pharmacological
  • Cease precipitants (drugs)
  • Diuretic
    • Thiazide
      • Corrects hyperosmolar plasma by driving natriuresis
      • Relative hypovolaemia results in RAAS activation, ↓ GFR, and ↓↓ UO
    • Amiloride
      Offsets potassium loss from thiazide.
  • Exogenous ADH
    DDAVP 1-4μg IV daily.
  • Other agents
    • NSAID
      ↓ GFR and therefore ↓ UO.
      • Synergistic with diuretics
      • Obvious risk of AKI
    • Chlorpropamide
      ↑ ADH release and renal ADH sensitivity.
    • Carbamazepine
      High doses ↓ UO in partial disease.

Supportive care:

• F
  • Electrolyte correction
    Replacement of magnesium, potassium, calcium, etc.
  • ↓ Solute intake
    ↓ Daily solute load results in a ↓ total UO, and may make it more manageable.
    • Salt restriction (<100mmol/day)
    • Protein restriction to minimum daily requirements

Marginal and Ineffective Therapies

• Clofibrate
  Superseded by DDAVP.

Anaesthetic Considerations

Complications

Prognosis

Key Studies

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References

1. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.