diabetes insipidus Flashcards
definition of DI
A disorder of inadequate secretion of or insensitivity to vasopressin (ADH)leading to hypotonic polyuria.
passage of >3L/day of dilute urine due to impaired water resorption by the kidney, because of reduced ADH secretion from posterior pit (cranial) or impaired response of the kidney to ADH (nephrogenic)
aetiology of DI
central/cranial - failure of ADH secretion by the posterior pituitary
nephrogenic - insensitivity of the collecting duct to ADH
aquaproins fail to activate and luminal membrane of collecting duct remains impermeable to water
= large vol of hypotonic urine and polydipsia
causes of central/cranial DI
idiopathic
tumour - pit tumour, craniopharyngioma, metastases
infilitrative - sarcoidosis, histiocytosis
autoimmune hypophysitis
infection - meningitis
vascular - aneurysm, sheehan syndrome
trauma - temporary if distal to the pituitary stalk, head injury, neurosurgery, hypophysectomy
DIDMOAD
congenital - defects in ADH gene
causes of nephrogenic DI
idiopathic
drugs - lithium, democlocycline
post obstructive uropathy
pyeloneophritis
pregnancy
osmotic diuresis - dm
inherited
metabolic - low K, high Ca
chronic renal disease
post-obstructive uropathy
DIDMOAD
Wolfram’s syndrome
diabetes insipidus, dm, optic atrophy and deafness
autosomal recessive with incomplete penetrance
WFS1 and ZCD2
wolframin - product of WFS1 a transmembrane protein in pancreatic B cells and neurons
epidemiology of DI
24yrs - median age of onset
sx of DI
polyuria
polydipsia
nocturia
enuresis and sleep disturbance in children
sx of hypernatrarmia (Lethargy, thirst, weakness, irritability, confusion, coma, and fits)
signs of DI
cranial DI - few signs if drink enough
UO >3L/24hr
if fluid intake
sign of cause - eg visual field defect
Ix for DI
blood
- UE
- Ca
- Na - may be high - dehydration
- increased plasma osmolarity
- decreased urine osmolarity
- Significant DI is excluded if urine to plasma (U:P) osmolality ratio is more than 2:1, provided plasma osmolality is no greater than 295mOsmol/kg.
- in primary polydipsia - dilutional hyponatraemia
- glucose - exclude dm
water deprivation test
water deprivation test for DI
restricted for 8hr
plasma and urine osmolarity measured every hour over 8hr
weigh pt hourly - monitor dehydration - stop if fall >3%
desmopressin given after 8h (2ug IM) - urine osmolarity measured
normal response to water deprivation test
increase plasma osmolarity and ADH = water resorption in collecting ducts = urine concentrated osmolarity >600mosmol/Kg
U:P ratio >2
DI response to water deprivation test
urine unable to concentrate,
urine osmolarity <400mosmol/kg
cranial DI response to water deprivation test
urine unable to concentrate, urine osmolarity <400mosmol/kg
urine osmolarity increases >50% with desmopressin
nephrogenic DI response to water deprivation test
urine unable to concentrate, urine osmolarity <400mosmol/kg
nephrogenic urine osmolarity increases <45% with desmopressin
Mx for DI
treat cause
cranial
- MRI head
- desmopressin (DDAVP) 10ug/day (vasopressin analogue)
- in mild - chlorpropamide or carbamazepine - potentiate effects of residual vasopressin
nephrogenic
- sodium and/or protein restriction may help polyuria
- thiazide diuretics bendroflumethiazide 5mg PO/24h
- NSAIDS lower urine volume and plasma Na+ by inhibiting prostaglandin synthase: prostaglandins locally inhibit the action of ADH
complications of DI
hypernatraemic dehydration
excess desmopression therapy might = hyponat
prognosis for DI
variable depending on cause
cranial may be transient from head trauma
cure may be possible on removal of cause - eg tumour/drug
ddx for DI
dm
diuretics
lithium
primary polydipsia
sx of polydipsia and polyuria and dilute urine
cause - poorly understood
may be associated with schizophrenia or mania (+- lithium therapy) or, rarely, hypothalamic disease (neurosarcoid; tumour; encephalitis; brain injury; HIV encephalopathy)
kidneys lose ability to fully concentrate the urine, due to wash out of normal concentrating gradient in the renal medulla
emergency Mx of DI
urgent plasma UE, serum and urine osmolarities
monitor urine output carefully - check UE twice daily
IVI to keep up with UO
if severe hypernatraemia - dont lower Na rapidly -> cerebral oedema and brain injury
. If Na+ is ≥170, use 0.9% saline initially—this contains 150mmol/L of sodium. Aim to reduce Na+ at a rate of less than 12mmol/L per day. Use of 0.45% saline can be dangerous
Desmopressin 2mcg IM (lasts 12–24h) may be used as a therapeutic trial.
primary polydipsia response to water deprivation test
Urine concentrates, but less than normal, eg >400–600mOsmol/kg
