Diabetes insipidus Flashcards
Define diabetes insipidus. What are the two types?
Disorder characterised by polydipsia, polyuria, and formation of inappropriately hypotonic (dilute) urine.
Two types exist: central diabetes insipidus (DI), due to reduced synthesis or release of arginine vasopressin (AVP) from the hypothalamo-pituitary axis; and nephrogenic DI, due to renal insensitivity to AVP.
What are the risk factors for diabetes insipidus?
Central:
- Pituitary surgery
- Craniopharyngioma
- Infiltrative pituitary stalk lesions
- TBI
- SAH
- Congenital hypothalamo-pituitary defects
- AI disorders
- Wolfram syndrome
Nephrogenic:
- lithium therapy
- CKD
- chronic hypercalcaemia
- hypokalaemia
genetic mutations can cause inherited forms of both types
What is the aetiology of central diabetes insipidus?
Acquired
- Pituitary surgery for adenoma - transient or permanent DI
- Craniopharyngioma
- Head injury - most transient
- Pituitary stalk lesions - common in Langerhans’ cell histocytosis
- AI disorders - Hashimoto’s thyroiditis, DM type 1
- CNS infection - meningitis/encephalitis
- Medications - phenytoin, temozolamide
- CO poisoning
Congenital
- Malformations of the pituitary/hypothalamus
- Wolfram syndrome
- AVP-neurophysin gene mutations
What is the aetiology of nephrogenic diabetes insipidus?
Acquired:
- Medication - lithium, demeclocycline, cisplatin, colchicine, gentamicin, rifampin
- Systemic disease, electrolyte imbalance, post-obstructive uropathy - CKD, renal sarcoidosis, renal amyloidosis, ureteric obstruction
Inherited
- AVPR2 mutation - mediates antidiuretic action of AVP - 90% MALE because X linked
- AQP2 gene mutations
Pregnancy
- Osmotic thresholds for thirst and AVP release are altered in pregnancy - AVP is cleared more quickly so DI can be masked in pregnancy
What are the signs and symptoms of DI?
- polyuria - 3-20L a day
- polydipisa
- nocturia
- dehydration
- dilute urine
Physical examination:
- dry mucous membranes
- irritability, restlessness, lethargy, muscle twitching, spasticity - hypernatraemia
- pituitary CNS effects
- other manifestations of disease
What investigations would you do for diabetes insipidus?
Urine osmolality - low (<300mOsm/kg)
Serum osmolality - high
Water deprivation and desmopressin stimulation test -
- Water deprivation test- confirms inability to concentrate urine properly - <300 mOsm/kg
- Desmopressin (AVP) stimulation test - only if WDT is positive; kidneys should respond to increase urine osmolality to >750mOsm/kg otherwise nephrogenic.
Other:
- U&Es including calcium
- serum sodium - elevated sodium with hypotonic urine strongly suggests DI
- glucose - exclude DM
- 24hr urine collection - >3L
Other:
- Urine dipstick - negative for glycosuria; proteinuria if underlying renal disease
- cranial MRI
- other hormones
How would you manage central diabetes insipidus?
- Desmopressin (DDAVP) - long acting analogue of AVP. Start at lowest possible dose. There is risk of transient SIADH.
- Oral/IV fluids - hypotonic fluid replacement is required. IV dextrose 5% and 0.45% NaCl may be required.
How do you manage nephrogenic diabetes insipidus?
- Sodium restriction- low sodium diet (<500mg/day), low protein; may reduce output
- Thiazide diuretic and indometacin may reduce urine output. Nephrologist should prescribe this.
Other:
- Maintain adequate fluid intake - to match the output and insensible losses e.g. 12L
- Treat underlying cause e.g. discontinue drug, treat hypercalcaemia/hypokalaemia
- Consult nephrology specialist
What are the complications of diabetes insipidus? What is the prognosis?
Hypernatraemia - in impaired access to water. Normal thirst response is protective against this.
Thrombosis - increased risk due to hypernatraemia and dehydration
Bladder and renal dysfunction
Iatrogenic hyponatraemia - on DDAVP. Most remains asymptomatic.
Outcome - depends on underlying aetiology. DI in pregnancy resolves with delivery.
What is Wolfram’s syndrome?
DIDMOAD is the association of:
- cranial Diabetes Insipidus,
- Diabetes Mellitus,
- Optic Atrophy
- and Deafness
