Arginine vasopressin deficiency & resistance AKA Diabetes insipidus (E&M) Flashcards
Define diabetes insipidus.
Condition in which kidneys are unable to concentrate urine due to inadequate secretion or sensitivity to ADH/AVP, resulting in production of large volumes of dilute urine
What is the role of ADH (AVP)?
Increases water reabsorption into blood in collecting duct via V2 receptors
What are the two types of diabetes insipidus?
- central diabetes insipidus (AVP deficiency) - failure of ADH secretion by the posterior pituitary
- nephrogenic diabetes insipidus (AVP resistance) - insensitivity of the collecting duct to ADH (defective V2 receptors)
What are the causes of central diabetes insipidus (AVP deficiency)? (10)
- congenital (defects in ADH gene)
- tumours (pituitary tumour, craniopharyngioma, metastases)
- infiltrative (sarcoidosis, TB)
- infection (meningitis)
- vascular (aneurysms, Sheehan syndrome, subarachnoid haemorrhage)
- trauma (head injury, surgery)
- hypophysectomy
- autoimmune hypophysitis
- hereditary haemochromatosis
- Wolfram syndrome
What are some causes of nephrogenic diabetes insipidus (AVP resistance)? (5)
- lithium therapy
- inherited (AVP2 gene)
- electrolyte imbalances (hypercalcaemia, hypokalaemia)
- CKD
- idiopathic
What are both forms of diabetes insipidus associated with?
Hypernatraemia (due to reduced water reabsorption by blood)
What are the clinical features of diabetes insipidus? (4)
- polyuria - with very dilute urine
- nocturia - with sleep disturbance
- polydipsia
- enuresis in children
- dehydration - tachycardia, postural hypotension, reduced skin turgor, dry mucus membranes
What are the signs of dehydration seen in diabetes insipidus, and when do they occur?
If fluid intake < output; does not present with many signs if patient drinks sufficiently to maintain adequate fluid levels:
- tachycardia
- postural hypotension
- reduced skin turgor
- dry mucus membranes
When do patients present with sensorineural deafness and visual failure with diabetes insipidus?
Wolfram syndrome - DM, central DI, optic atrophy and sensorineural deafness
What are the first-line investigations for diabetes insipidus? (4)
- urine osmolality
- serum osmolality
- serum glucose
- serum sodium
What are urine and serum osmolality like in diabetes insipidus?
- urine osmolality = low
- serum osmolality = high
What confirmatory test can we do to diagnose diabetes insipidus?
Water deprivation test
- stage 1: fluid deprivation for 8h with plasma and urine osmolality measured every hour
- weigh the patient hourly to monitor dehydration
- STOP the test if body weight falls >3%
- stage 2: after 8h, test stopped if urine osmolality >600mOsm/kg. If <600mOsm/kg, continue to differentiate cranial from nephrogenic DI
- desmopressin (synthetic vasopressin) is given and urine osmolality measured hourly for next 4h
- CDI - urine osmolality will rise
- NDI - urine osmolality will remain low
What if urine osmolality corrects itself in water deprivation test?
May be psychogenic polydipsia
(if >600mOsm/kg at 8h, as ADH is available to reabsorb water into body and concentrate urine)
What if urine osmolality does not correct itself in water deprivation test?
Administer desmopressin (ddAVP) after 8h:
- cranial DI - urine osmolality will rise
- nephrogenic DI - urine osmolality will remain low
What scan can we do in diabetes insipidus?
MRI to look for brain/pituitary tumour
What do bloods (electrolytes) show in diabetes insipidus? (4)
- hypernatraemia
- hypokalaemia - ECG changes:
- T-wave inversion
- QTc prolongation
- U waves
- hypercalcaemia if nephrogenic DI
- normal blood glucose - to exclude DM
What if hyponatraemia is present when investigating for diabetes insipidus?
Psychogenic polydipsia - in context of low urine osmolality
What ECG changes might be seen in diabetes insipidus?
Due to hypokalaemia:
- inverted T waves
- QTc prolongation
- U waves
What antibodies could we look for in diabetes insipidus?
Anti-TPO antibodies as central diabetes insipidus (AVP deficiency) is associated with Hashimoto’s thyroiditis
What are some differential diagnoses for diabetes insipidus? (5)
- psychogenic polydipsia
- DM
- diuretic use
- hypercalcaemia
- primary polydipsia:
- urine osmolality after fluid deprivation - high
- urine osmolality after desmopressin - high
What is the diagnostic criteria for psychogenic polydipsia?
- serum osmolality normal
- urine osmolality slightly lower than a normal person
- hyponatraemia
What is the diagnostic criteria for diabetes insipidus?
- serum osmolality high
- urine osmolality low (<400mOsm/kg)
- urine osmolality rises >50% following desmopressin in cranial DI
- urine osmolality will not rise following ddAVP in nephrogenic DI
How do we manage hypernatraemia in diabetes insipidus?
Oral or IV fluids (prevents dehydration)
What is a complication of correcting chronic hypernatraemia with fluids too fast (diabetes insipidus)?
Predisposes to cerebral oedema
How do we manage central diabetes insipidus (AVP deficiency)?
- MRI head - identify cause
- intranasal desmopressin
- if mild - chlorpropamide or carbamazepine to potentiate the effects of any residual AVP
- oral/IV fluids (hyperNa)
How do we manage nephrogenic diabetes insipidus (AVP resistance)?
- discontinue causative agent if medication-induced (lithium)
- thiazide diuretics (benzofluorothiazide) - helps polyuria
- adequate fluid intake
- sodium (and/or protein) restriction - helps polyuria
- NSAIDs lower urine volume and plasma Na by inhibiting prostaglandin synthesis
What drugs do thiazide diuretics (benzofluorothiazide) interact badly with?
Digoxin - causes arrhythmias, N&V, lethargy, anorexia, yellow-green vision, confusion, malaise
What are some complications of diabetes insipidus? (4)
- hypernatraemia (irritability, restless, lethargy, muscle twitching, spasticity, hyperreflexia, delirium, seizures, coma)
- iatrogenic hyponatraemia (desmopressin side effect)
- thrombosis
- bladder and renal dysfunction
