Arginine vasopressin deficiency & resistance AKA Diabetes insipidus (E&M) Flashcards

1
Q

Define diabetes insipidus.

A

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

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2
Q

What is the role of ADH (AVP)?

A

Increases water reabsorption into blood in collecting duct via V2 receptors

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3
Q

What are the two types of diabetes insipidus?

A
  • 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)
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4
Q

What are the causes of central diabetes insipidus (AVP deficiency)? (10)

A
  • 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
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5
Q

What are some causes of nephrogenic diabetes insipidus (AVP resistance)? (5)

A
  • lithium therapy
  • inherited (AVP2 gene)
  • electrolyte imbalances (hypercalcaemia, hypokalaemia)
  • CKD
  • idiopathic
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6
Q

What are both forms of diabetes insipidus associated with?

A

Hypernatraemia (due to reduced water reabsorption by blood)

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7
Q

What are the clinical features of diabetes insipidus? (4)

A
  • polyuria - with very dilute urine
  • nocturia - with sleep disturbance
  • polydipsia
  • enuresis in children
  • dehydration - tachycardia, postural hypotension, reduced skin turgor, dry mucus membranes
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8
Q

What are the signs of dehydration seen in diabetes insipidus, and when do they occur?

A

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
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9
Q

When do patients present with sensorineural deafness and visual failure with diabetes insipidus?

A

Wolfram syndrome - DM, central DI, optic atrophy and sensorineural deafness

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10
Q

What are the first-line investigations for diabetes insipidus? (4)

A
  • urine osmolality
  • serum osmolality
  • serum glucose
  • serum sodium
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11
Q

What are urine and serum osmolality like in diabetes insipidus?

A
  • urine osmolality = low
  • serum osmolality = high
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12
Q

What confirmatory test can we do to diagnose diabetes insipidus?

A

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
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13
Q

What if urine osmolality corrects itself in water deprivation test?

A

May be psychogenic polydipsia

(if >600mOsm/kg at 8h, as ADH is available to reabsorb water into body and concentrate urine)

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14
Q

What if urine osmolality does not correct itself in water deprivation test?

A

Administer desmopressin (ddAVP) after 8h:

  • cranial DI - urine osmolality will rise
  • nephrogenic DI - urine osmolality will remain low
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15
Q

What scan can we do in diabetes insipidus?

A

MRI to look for brain/pituitary tumour

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16
Q

What do bloods (electrolytes) show in diabetes insipidus? (4)

A
  • hypernatraemia
  • hypokalaemia - ECG changes:
    • T-wave inversion
    • QTc prolongation
    • U waves
  • hypercalcaemia if nephrogenic DI
  • normal blood glucose - to exclude DM
17
Q

What if hyponatraemia is present when investigating for diabetes insipidus?

A

Psychogenic polydipsia - in context of low urine osmolality

18
Q

What ECG changes might be seen in diabetes insipidus?

A

Due to hypokalaemia:

  • inverted T waves
  • QTc prolongation
  • U waves
19
Q

What antibodies could we look for in diabetes insipidus?

A

Anti-TPO antibodies as central diabetes insipidus (AVP deficiency) is associated with Hashimoto’s thyroiditis

20
Q

What are some differential diagnoses for diabetes insipidus? (5)

A
  • psychogenic polydipsia
  • DM
  • diuretic use
  • hypercalcaemia
  • primary polydipsia:
    • urine osmolality after fluid deprivation - high
    • urine osmolality after desmopressin - high
21
Q

What is the diagnostic criteria for psychogenic polydipsia?

A
  • serum osmolality normal
  • urine osmolality slightly lower than a normal person
  • hyponatraemia
22
Q

What is the diagnostic criteria for diabetes insipidus?

A
  • 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
23
Q

How do we manage hypernatraemia in diabetes insipidus?

A

Oral or IV fluids (prevents dehydration)

24
Q

What is a complication of correcting chronic hypernatraemia with fluids too fast (diabetes insipidus)?

A

Predisposes to cerebral oedema

25
Q

How do we manage central diabetes insipidus (AVP deficiency)?

A
  • MRI head - identify cause
  • intranasal desmopressin
  • if mild - chlorpropamide or carbamazepine to potentiate the effects of any residual AVP
  • oral/IV fluids (hyperNa)
26
Q

How do we manage nephrogenic diabetes insipidus (AVP resistance)?

A
  • 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
27
Q

What drugs do thiazide diuretics (benzofluorothiazide) interact badly with?

A

Digoxin - causes arrhythmias, N&V, lethargy, anorexia, yellow-green vision, confusion, malaise

28
Q

What are some complications of diabetes insipidus? (4)

A
  • hypernatraemia (irritability, restless, lethargy, muscle twitching, spasticity, hyperreflexia, delirium, seizures, coma)
  • iatrogenic hyponatraemia (desmopressin side effect)
  • thrombosis
  • bladder and renal dysfunction