Central diabetes insipidus 

Diabetes insipidus (DI)

• is a condition caused by loss of the effect of antidiuretic hormone on the collecting ducts of the kidneys, resulting in loss of free water.

• diabetes insipidus can be
  • central
  • nephrogenic

• Normal physiology
  • Vasopressin/antidiuretic hormone(ADH)  is produced in the hypothalamus and travels along nerve fibers to the posterior pituitary, where it is stored and released
  • Increased plasma osmolality stimulates release of ADH
  • ADH promotes reabsorption of water in the collecting duct of nephrons via translocation of aquaporins (water channels) to the plasma membrane from internal sites within the cells

Diabetes insipidus

• central DI (CDI) results from causes that impair the synthesis, transport, or release of ADH
• nephrogenic DI (NDI) results from receptor, or downstream, unrepsonsiveness to circulating ADH
• loss of ADH effect results in polyuria, dehydration, hypernatremia and a hyperosmolar state

CAUSES OF CENTRAL DIABETES INSIPIDUS

• Acquired
  • Surgery (transsphenoidal) – common
  • TBI – common
  • Idiopathic
  • Autoimmune
  • Tumours (suprasellar, lung, breast, lymphoma, leukaemia)
  • Hypoxic brain injury
  • Brain stem death
  • Profound hyponatraemia -> cerebral oedema
  • Radiotherapy
  • Inflammatory conditions – sickle cell, sarcoid, Wegener’s, histiocytosis X
  • Infections – Tb, abscess, encephalitis, meningitis
  • Vascular disease – CVA, SAH, Sheehan’s syndrome, pituitary apoplexy

• Congenital
  • Autosomal dominant mutation in ADH production
  • Wolfram syndrome

ASSESSMENT

• History
  • Polyuria
    • urine output >4 mL/kg/hr (averaged over a 6 hour duration)
  • Nocturia or new onset nocturnal enuresis
  • Polydipsia
    • drinking overnight
    • persistent focus on drinking any fluid (which is unusual for child)
    • drinking from unusual sources (eg animal bowls)
  • Loss of weight (fluid replacing food intake and dehydration)
  • Presence of intercurrent illness in a child with known DI (eg URTI, gastroenteritis)
  • Past or family history of DI
  • Head injury
  • Constipation (from dehydration)
  • Neurological symptoms (eg early morning headaches, vomiting, altered sensation, weakness)
  • Medications (eg diuretics)
• Examination
  • Dehydration
  • Neurological symptoms or signs (of an underlying disease)
  • Fundal examination and visual fields

DIAGNOSIS

• Key findings
  • plasma hyperosmolality (can be mild in partial DI)
  • hypernatraemia (na >155 mM)
  • polyuria (>3L/24h)
  • urine osmolality < 200 mOsm/kg
• Investigate for underlying cause

• MANAGEMENT
  • treat hypernatraemia
  • address deficit in total body H2O (dehydration and hypovolaemia)
  • supplement ADH
  • consider associated anterior pituitary dysfunction
  • treat underlying cause

• PROGNOSIS

• Post-traumatic diabetes insipidis is associated with:
  • more severe trauma
  • cerebral edema
  • lower GCS scores
  • higher mortality rate
  • 57-69% overall
  • 86-90% if early-onset (<3 days after injury)
  • brain death (DI is present in ~80% of brain dead TBI patients)
  • hypernatraemia correlates with higher mortality (e.g. Na >160 mmol/L)