diabetes insipidus

Question 1

definition of DI

Answer 1

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)

Question 2

aetiology of DI

Answer 2

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

Question 3

causes of central/cranial DI

Answer 3

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

Question 4

causes of nephrogenic DI

Answer 4

idiopathic

drugs - lithium, democlocycline

post obstructive uropathy

pyeloneophritis

pregnancy

osmotic diuresis - dm

inherited

metabolic - low K, high Ca

chronic renal disease

post-obstructive uropathy

Question 5

DIDMOAD

Answer 5

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

Question 6

epidemiology of DI

Answer 6

24yrs - median age of onset

Question 7

sx of DI

Answer 7

polyuria

polydipsia

nocturia

enuresis and sleep disturbance in children

sx of hypernatrarmia (Lethargy, thirst, weakness, irritability, confusion, coma, and fits)

Question 8

signs of DI

Answer 8

cranial DI - few signs if drink enough

UO >3L/24hr

if fluid intake

sign of cause - eg visual field defect

Question 9

Ix for DI

Answer 9

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

Question 10

water deprivation test for DI

Answer 10

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

Question 11

normal response to water deprivation test

Answer 11

increase plasma osmolarity and ADH = water resorption in collecting ducts = urine concentrated osmolarity >600mosmol/Kg

U:P ratio >2

Question 12

DI response to water deprivation test

Answer 12

urine unable to concentrate,

urine osmolarity <400mosmol/kg

Question 13

cranial DI response to water deprivation test

Answer 13

urine unable to concentrate, urine osmolarity <400mosmol/kg

urine osmolarity increases >50% with desmopressin

Question 14

nephrogenic DI response to water deprivation test

Answer 14

urine unable to concentrate, urine osmolarity <400mosmol/kg

nephrogenic urine osmolarity increases <45% with desmopressin

Question 15

Mx for DI

Answer 15

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

Question 16

complications of DI

Answer 16

hypernatraemic dehydration

excess desmopression therapy might = hyponat

Question 17

prognosis for DI

Answer 17

variable depending on cause

cranial may be transient from head trauma

cure may be possible on removal of cause - eg tumour/drug

Question 18

ddx for DI

Answer 18

dm

diuretics

lithium

Question 19

primary polydipsia

Answer 19

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

Question 20

emergency Mx of DI

Answer 20

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.

Question 21

primary polydipsia response to water deprivation test

Answer 21

Urine concentrates, but less than normal, eg >400–600mOsmol/kg