Neurohypophysial disorders

Question 1

What are the principle effects of vasopressin?

Answer 1

It is an antidiuretic (ADH): acts on V2 receptors on renal cortical and medullary collecting ducts, stimulates synthesis and assembly of aquaporin 2, resulting in increased water transport and increased water reabsorption.
Other actions:
-vasoconstrictor activity via V1a receptors
-corticotrophin (ACTH) release via V1b receptors
-factor VIII and von Willebrand factor via V2 receptors
-central effects

Question 2

How is vasopressin release regulated?

Answer 2

Vasopressin release is regulated by osmoreceptors (neurones) located in the organum vasculosum, which project onto the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The osmoreceptors are very sensitive to changes in extracellular osmolality.

Question 3

What are the two types of diabetes insipidus?

Answer 3

Cranial/central- occurs where there is an absence or lack of circulating vasopressin.
Nephrogenic- occurs where there is end-organ (kidney) resistance to vasopressin.

Question 4

What effects does oxytocin have?

Answer 4

Constriction of myometrium at parturition
Milk ejection reflex
Central effects
Acts on oxytocin receptors

Question 5

What is the aetiology of cranial diabetes insipidus?

Answer 5

Acquired (more common): damage to neurohypophyseal system, e.g. by traumatic brain injury, pituitary surgery, pituitary tumours, craniopharyngioma, metastasis to the pituitary gland (e.g. breast), granulomatous infiltration of median eminence (e.g. TB, sarcoidosis).
Congenital (rare)- usually receptor gene mutations.
Idiopathic.

Question 6

What is the aetiology of nephrogenic diabetes insipidus?

Answer 6

Congenital (rare)- e.g. mutation in gene encoding V2 receptor, aquaporin 2 type water channel.
Acquired- drugs, e.g. lithium.

Question 7

What are the signs and symptoms of diabetes insipidus?

Answer 7

Polyuria
Hypoosmolar (dilute) urine
Polydipsia
Dehydration (and consequences) if fluid intake not maintained- can lead to death
Possible disruption to sleep with associated problems

Question 8

What is psychogenic polydipsia?

Answer 8

Most frequently seen in psychiatric patients, aetiology unclear, may reflect anticholinergic effects of medication- ‘dry mouth’.
Can be in patients told to ‘drink plenty’ by healthcare professionals.
Excess fluid intake (polydipsia) and excess urine output (polyuria), but unlike DI, ability to secrete vasopressin in response to osmotic stimuli is preserved.

Question 9

What is a fluid deprivation test, what is it used for and what does it show?

Answer 9

Stimulates vasopressin system in normal patients- urine will be concentrated so urine osmolality and plasma osmolality stay normal.
In a psychogenic polydipsia patient, urine osmolality is slightly lower because the osmotic gradient has started to be washed out over a long period of time.
With DI, there is little/no change after a fluid deprivation test.

Question 10

What can desmopressin (DDAVP) be used for?

Answer 10

To distinguish between cranial and nephrogenic diabetes insipidus. Vasopressin receptors in cranial DI still work so will be stimulated, but nephrogenic DI patients already have vasopressin- it’s their unresponsive receptors that are the problem- so giving DDAVP has no effect on nephrogenic DI.

Question 11

What are the biochemical features of diabetes insipidus?

Answer 11

Hypernatraemia
Raised urea
Increased plasma osmolality
Hypo-osmolar (dilute) urine, i.e. low urine osmolality

Question 12

What are the biochemical features of psychogenic polydipsia?

Answer 12

Mild hyponatraemia- excess water intake
Low plasma osmolality
Hypo-osmolar (dilute) urine, i.e. low urine osmolality

Question 13

What is desmopressin used to treat?

Answer 13

It is a selective V2 receptor peptidergic agonist, administered nasally, orally or subcutaneously. It causes a reduction in urine volume and concentration in cranial diabetes insipidus.

Question 14

What is nephrogenic diabetes insipidus treated with?

Answer 14

Thiazides, e.g. bendroflumethiazide.

Question 15

What is the syndrome of inappropriate ADH (SIADH)?

Answer 15

Plasma vasopressin concentration is inappropriately high for the existing plasma osmolality.

Question 16

What are the signs of SIADH?

Answer 16

Raised urine osmolality
Decreased urine volume (initially)
Hyponatraemia, mainly due to increased water reabsorption.

Question 17

What are the symptoms of SIADH?

Answer 17

Can be symptomless.
If plasma sodium concentration is <120mM, expect symptoms of generalised weakness, poor mental function and nausea.
If plasma sodium concentration is <110mM, expect confusion leading to coma and death.

Question 18

What are the causes of SIADH?

Answer 18

CNS:

• Subarachnoid haemorrhage
• Stroke
• Tumour
• Traumatic brain injury

Pulmonary disease:

• Pneumonia
• Bronchiectasis

Malignancy:
-Lung (small cell)

Drug-related:

• Carbamazepine
• SSRI

Idiopathic.

Question 19

What treatment is used for SIADH?

Answer 19

Appropriate treatment (e.g. surgery for tumour)- cause must be established.
To reduce immediate concern, e.g. hyponatraemia, immediate treatment is fluid restriction and long-term treatment is with drugs that prevent vasopressin action in kidneys: induce nephrogenic DI, i.e. reduce renal water reabsorption, using demeclocycline; inhibit action of ADH using V2 receptor antagonists.

Question 20

What are SIADH vaptans?

Answer 20

Non-competitive V2 receptor antagonists used to treat hyponatraemia associated with SIADH, which inhibit AQP2 synthesis and transport to collecting duct apical membrane- prevent renal water reabsorption.
Aquaresis- solute-sparing renal excretion of water, contrast with diuresis which produces simultaneous electrolyte loss.