Diabetes Insipidus

Question 1

What is the epidemiology of diabetes insipidus?

Answer 1

Uncommon, 1:250,000

Lithium induced nephrogenic DI is the most common; inherited forms are <10%

Question 2

What are the causes of neurogenic DI?

Answer 2

• Problem originates in the brain (hypothalamus or posterior pituitary) as a result of a decrease in the levels of circulating ADH
• Familial = autosomal dominant mutations in the vasopressin gene (AVP-NPII)
• Acquired = more common:
• Idiopathic (25% cases)
• Tumours (pituitary adenoma, craniopharyngiomas, metastatses)
• Trauma
• Neurosurgery
• Meningitis
• Vascular causes e.g. Sheehan’s syndrome
• Sarcoidosis
• Haemochromatosis

Question 3

What are the causes of nephrogenic DI

Answer 3

• Anything interferes with ADH binding in the kidney
• Familial = X-linked recessive ADH receptor gene mutations; autosomal recessive mutations in aquaporin-2 (responsible for reabsorption of water)
• Acquired = more common:
• Metabolic e.g. hypercalcaemia, hyperglycaemia, hypokalaemia
• Drugs e.g. lithium, demeclocycline
• Chronic renal disease
• Amyloidosis
• Post obstructive uropathy

Question 4

What other types of DI are there?

Answer 4

• Dispogenic DI = damage of thirst mechanism due to hypothalamic disease/trauma; patient excessively thirsty regardless of fluid status - large volumes of water ingested so ADH suppressed and urine output increased
• Gestational DI = placenta produces vasopressinase which degrades ADH, too much of this breakdown reduces circulating ADH
• Primary polydipsia = individual consuming large amounts of water so producing a large amount of dilute urine, commonly a behavioural disorder; similar to DI but differentiated with a fluid deprivation test (as will stop producing so much urine)

Question 5

How does DI present?

Answer 5

Excessive urination
Excessive thirst - especially for ice-cold water
Nocturia
Dehydration (dizziness, dry mouth, headache, cap refill long)
Hypotension
Dilute urine

Question 6

How do you investigate DI?

Answer 6

24-hr urine collection:
- Typically >3000ml of urine in 24hrs

Biochemistry:

• Plasma glucose - rule out DM
• cCa - to rule out hypercalcaemia (e.g. secondary to hyperparathyroidism)
• U+E - renal function and electrolyte abnormalities
• Urine specific gravity
• Simultaneous plasma and urine osmolality

Fluid deprivation test:

• Patient deprived of fluids for 8hrs or the loss of 5% body weight then give desmopressin
• There is a table comparing urine osmolalities before and after desmopressin which will indicate the likely diagnosis
• Neurogenic - osmolality will increase after desmopressing; nephrogenic - osmolality will NOT increase

MRI brain:
- Pituitary, hypothalamus and pineal gland - to assess for cranial causes

Renal tract USS:
- or UV pyelogram - used to assess for post obstructive uropathy

Question 7

How do you manage neurogenic DI?

Answer 7

Replacement with synthetic ADH - desmopressin (PO, intranasally, parentrally)

Monitoring:

• For signs of desmopresin overdose e.g. hyponatraemia signs
• Serum sodium osmolality every 1-3 months

Question 8

How do you manage nephrogenic DI?

Answer 8

If urine volume <4L/24hrs and patient not severely dehydrated, may not need treatment

Patients should drink enough to satisfy their thirst and not be dehydrated

Correct any metabolic abnormalities

Stop any drugs that are causative

May be prescribed amiloride, thiazide diuretics + NSAID to reduce the amount of urine

Sometimes high dose desmopressin is used for mild-moderate nephrogenic DI depending on the cause/how responsive the kidneys are to ADH