Diabetes insipidus

Background/Epidemiology

• Rare disorder characterised by persistent excretion of excessive quantities of dilute urine and by thirst.
• 2 types
  • Cranial
    • deficient ADH production
    • Causes include tumours, surgery/injury, infection, radiotherapy, Sheehan’s syndrome; inherited disorders e.g. Wolfram syndrome; idiopathic
  • Nephrogenic
    • deficient response to ADH
    • causes include electrolyte disturbances (hypokalaemia, hypercalcaemia); CKD; drugs e.g. lithium; renal tubular acidosis; congenital disorders; pregnancy

Clinical Features

• Polyuria and polydipsia (can be severe)
  • Low specific gravity and osmolarity urine
  • If the patient is unable to replace fluids orally, DI can dehydrate patients very quickly and can be lethal
• NB If there is associated cortisol deficiency, DI may only present after this has been corrected

Investigations

• ADH levels can be measured (undetectable in DI; can be measured after infusion of hypertonic (5%) saline solution), however, most centres use a water deprivation test
  • Process
    • Patient is asked to drink normalls but omit caffeine (tea/coffee) and smoking on the test day
    • No fluids from 7:30 am
    • Measure body weight, plasma and urine osmolarity at 8:30 then every 2 hours, recording also urine volume and a thirst score
    • Stop if the patient loses 3% of body weight
    • If plasma osmolality reaches >300mOsm/kg and urine osmolality <600mOsm/kg, administer IM desmopressin (DDAVP)
      • confirms DI
      • if urine osmolality rises by 50% after desmopressin, DI is likely cranial (if not, DI is more likely nephrogenic
    • Primary polydipsia is suggested by low plasma osmolality at the start of the test (avoid desmopressin where possible)
      • plasma osmolality is also low (not high)
• If cranial DI,
  • test anterior pituitary function and image using MRI
• In nephrogenic DI
  • U&Es, calcium, renal function and possibly imaging of the renal tract (+/- biopsy)

Management

• Cranial DI
  • Desmopressin (can be oral or intranasal spray)
    • Titrate the dose to manage symptoms appropriately (i.e. reducing nocturia, avoiding excess treatment)
• Nephrogenic
  • Correct any causes e.g. drugs, metabolic abnormality
  • Diuretics- Thiazide diuretics +/- Amiloride
  • NSAIDS can also be used, although care should be taken if the underlying cause is kidney injury, as these may worsen glomerular filtration rate and thus kidney function.

Other causes of polyuria and polydipsia

• Primary polydipsia (most common)- no associated hormone impbalance