Posterior Pituitary Gland ✅ Flashcards
What is the posterior pituitary also known as?
The neurohypophysis
What is the posterior pituitary derived from?
Neural ectoderm
What is the posterior pituitary formed from?
Neuronal projections (axons) of magnocellular neurosecretory cells
Where do the neuronal projections forming the posterior pituitary extend from?
The supraoptic and paraventricular nuclei of the hypothalamus
What bridges the hypothalamic and hypophyseal systems?
The infundibular or pituitary stalk
What hormone is synthesised in the posterior pituitary?
Arginine vasopressin (AVP)
What is AVP also known as?
Anti-diuretic hormone (ADH), or vasopressin
Where in the pituitary is ADH synthesised?
In neurons which originate in the supraoptic and paraventricular nuclei
Where do some paraventricular neurons end?
At the median eminence
What happens where paraventricular neurons end at the median eminence?
ADH is released into the hypophyseal circulation
Where do magnocellular neurons of the supraoptic and paraventricular nuclei end?
In the posterior pituitary
What happens where the magnocellular neurons of the supraoptic and paraventricular nuclei end in the posterior pituitary?
ADH is released into the systemic circulation
In what form is ADH synthesised?
In preprohormone formant
Where is ADH preprohormone synthesised?
In magnocellular neurones
What happens to ADH preprohormone after synthesis?
A signal peptide is cleaved, to form a prohormone
What happens to the prohormone of ADH after formation?
It folds and places ADH into a binding pocket of neurophysin
What does placing ADH into a binding pocket facilitate?
The production of high density neurosecretory granules
What happens to the neurosecretory granules of ADH?
They are transported to the posterior pituitary
What happens to the granules after they are transported to the posterior pituitary?
Vasopressin and neurophysin are released from the granules into the circulation after stimulation of vasopressinergic neurons
What is vasopressin secretion determined by?
- Plasma osmotic status
- Blood pressure
- Circulating volume
How does vasopressin act?
By binding to 3 GPCRs
How are pressor effects of vasopressin mediated?
By binding of vasopressin to V1 receptors in vascular smooth muscle
What is the main action of vasopressin?
Regulate blood volume control by regulating clearance of free water
How does vasopressin regulate clearance of free water?
Through binding to V2 receptors in the kidney
What is the result of vasopressin binding to V2 receptors in the kidney?
It stimulates expression of aquaporin 2
What does aquaporin 2 allow?
Reabsorption of water from the collecting duct along an osmotic gradient
What is another action of vasopressin?
Facilitates ACTH release from corticotrophs
How does vasopressin facilitate ACTH release from corticotrophs?
By binding to V3 receptors in the anterior pituitary gland
What is the most common disturbance of posterior pituitary function?
Diabetes insipidus
What are the types of diabetes insipidus?
- Cranial
- Nephrogenic
What is the problem in cranial diabetes insipidus?
Insufficient vasopressin release
What can cause insufficient vasopressin release?
Congenital or acquired defects of posterior pituitary anatomy
What is the problem in nephrogenic diabetes insipidus?
Renal resistance to vasopressin action
What needs to be determined from history in a child presenting with polyuria and a potential diagnosis of diabetes insipidus?
- Timing of onset of symptoms
- Details of mode of delivery
- Family history, particularly of diabetes mellitus
- Estimate of daily fluid intake
- What fluids they are drinking
- Details of symptoms suggestive of wider pituitary defects, and if there is past history of head injury or other brain insults e.g. surgery
- Presence of headaches or disturbance to vision
- History of renal disease
- Presence of other disorders
- Medication
Why is it important to know what fluids the child is drinking in suspected diabetes insipidus?
If only flavoured fluids, suggests habitual preference rather than defect in water homeostasis
If drinking usual fluids such as shampoo, or from unusual sources such as toilet bowls or flower pots, suggests extreme thirst, as occurs in diabetes insipidus
What other disorders should be enquired about in suspected diabetes insipidus?
- Impaired vision
- Hearing defects
- Symptoms suggestive of hypercalcaemia
What symptoms might be suggestive of hypercalcaemia?
- Anorexia
- Abdominal pain
- Constipation
What should clinical examination include in suspected diabetes insipidus?
- Hydration state
- Blood pressure
- Check for wider defects associated with abnormal pituitary function, e.g. growth and pubertal staging
- Craniofacial skeleton for midline defects
- Presence of enlarged kidneys
What is the most common cause of referral for assessment of fluid balance abnormalities?
Habitual excess drinking
How can habitual excess drinking be excluded?
Ask family to document fluid intake and output diary, with free access to water between meals and flavoured fluids only allowed at mealtimes
What should be done if excess fluid losses persist when the child is only allowed water between meals?
- Fasting serum sample for measurement of sodium, potassium, creatinine, osmolality, glucose, and calcium
- Paired fasting urine sample for glycosuria, proteinuria, sodium, and osmolality
How can paired urine/plasma testing confirm the presence of diabetes insipidus?
If inappropriately dilute urine (<759mOsm/kg) in presence of hyperosmolar state (serum osmolality >295mOsm/kg)
What should be done if paired urine/plasma testing does not confirm diabetes insipidus?
Further tests should be performed in a specialist centre
Why should further tests for diabetes insipidus be performed in a specialist centre?
As some of them are potentially dangerous
What further testing is done to when diabetes insipidus is suspected?
Child should be admitted for initial monitoring of fluid balance, then if indicated, water deprivation test
What happens in water deprivation test?
Fluids are withheld (usually for around 8 hours), until thirst cannot be tolerated anymore, weight loss exceeds 5%, or serum osmolality exceeds 295mOsm/kg. Once this is achieved and a urine sample obtained, test dose of desmopressin (DDVAP) given to monitor serum and urine osmolality over next few hours
What is the purpose of giving desmopressin following a water deprivation test?
Distinguish cranial from nephrogenic diabetes insipidus
How does giving desmopressin following a water deprivation test distinguish cranial from nephrogenic diabetes insipidus?
The presence of a urinary concentrating response confirms cranial
What is an alternative to the water deprivation test?
Hypertonic saline infusion test
What happens in the hypertonic saline infusion test?
5% saline is given IV until plasma osmolality exceeds 300mOsm/kg, following which plasma osmolality and plasma AVP are measured
What results of the hypertonic saline infusion test would suggest cranial diabetes insipidus?
Low levels of AVP when hyperosmolar
What results of the hypertonic saline infusion test would suggest nephrogenic diabetes insipidus?
High levels of AVP
What further investigations should be done if cranial diabetes insipidus is suggested by testing?
- Measurement of serum tumour markers ß-human chorionic gonadotrophin and α-fetoprotein
- MRI scanning of hypothalamo-pituitary axis
What are the categories of cranial DI?
- Triphasic pattern
- With intact thirst
- Anatomical defects
When does cranial DI with a triphasic pattern occur?
Following neurosurgery
What kind of neurosurgery in particular might cranial DI with triphasic pattern occur after?
For craniopharyngioma
What happens in triphasic pattern cranial DI?
DI may occur for up to 24 hours, followed by period of vasopressin excess for 2-4 days, then development of more permanent DI
Why is there a period of vasopressin excess in triphasic cranial DI?
Thought to be due to a necrotic posterior pituitary releasing vasopressin
When does cranial DI with intact thirst occur?
Inherited forms of DI, or where underlying pathology is confined to posterior pituitary and does not affect hypothalamic functioning
What is the most common inherited cause of DI?
Familial autosomal dominant neurohypophyseal DI
What is familial autosomal dominant neurohypophyseal DI usually due to?
Mutations in the neurophysin coding region or signal peptide, which impairs processing, folding, or dimerisation
What do the mutations causing familial autosomal dominant neurohypophyseal DI cause?
Accumulation of abnormal prohormone and degeneration of the magnocellular neurons
What does accumulation of abnormal prohormone and degeneration of the magnocellular neurons in familial autosomal dominant neurohypophyseal DI lead to?
Gradual but variable decline in vasopressin secretion in the first decade of life
Give another cause of inherited DI?
Wolfram syndrome
What is the inheritance pattern of Wolfram syndrome?
Autosomal dominant
What is Wolfram syndrome?
Association of diabetes insipidus with;
- Insulin dependant diabetes mellitus
- Optic atrophy
- Sensorineural deafness
What can cause inherited anatomical defects in posterior pituitary function?
- Congenital defects, e.g. septo-optic dysplasia
- In associated with other intracranial or midline abnormalities
What might MRI scanning show in inherited anatomical defects in posterior pituitary function?
Absent posterior pituitary signal, in addition to other cranial abnormalitites
What are the acquired causes of anatomical defects in posterior pituitary function?
- Tumours
- Infiltration
- Trauma
- Neurosurgery
- Autoimmune disease
- Hypoxia
- Idiopathic
What is the treatment for DI?
Desmopressin (DDAVP)
What routes can desmopressin be given?
- Orally
- Nasally
- Parenterally
How should desmopressin be started?
At low doses, and slowly increased
Why is it important desmopressin is started at low doses and slowly increased?
To avoid excess fluid retention
Should free access to fluids be allowed when starting desmopressin?
Yes
Why should free access to fluids be allowed when starting desmopressin?
To patient can correct inadequate therapy by increased fluid intake
Why does great care need to be taken when administering IV fluids to patients on desmopressin?
To avoid overhydration, as following desmopressin administration, patients cannot excrete an excess water load
Which type of DI is extremely difficult to manage?
Cranial DI with impaired thirst
What might cause cranial DI with impaired thirst?
- Impaired osmoreceptor function associated with neurodisability
- Following tumours or surgery
What does the management of cranial DI with impaired thirst require?
Careful balancing of desmopressin dose and fluid intake
Why does management of cranial DI with impaired thirst require careful balancing of fluid intake and desmopressin administration?
These patients cannot correct abnormal fluid balance through perceived effects of thirst
What is nephrogenic DI due to?
Renal resistance to AVP action
What can cause renal resistance to AVP action?
- Congenital abnormalities
- Drug induced
- Metabolic
- Aquaporin-mediated effects of renal disease associated with acute or chronic renal failure
Give an example of a drug induced cause of nephrogenic DI?
Lithium
What does lithium act on to cause nephrogenic DI?
Aquaporin 2
Give 3 metabolic causes of nephrogenic DI?
- Hyperglycaemia-associated osmotic diuresis
- Hypokalaemia
- Hypercalcaemia
What do the metabolic causes of nephrogenic DI act on?
Aquaporin 2 function
Why is nephrogenic DI difficult to treat?
- Free access to extra fluid is required
- Need attention to calorie intake
How can some relief of symptoms be provided in nephrogenic DI?
Thiazide diuretics in combination with amiloride or indomethacin
How do thiazides help in nephrogenic DI?
Thought to inhibit the NaCl cotransporter in the DCT, thereby increasing proximal tubular sodium and water reabsorption
What are the causes of SIADH?
- CNS system disorders
- Haemorrhage
- VP shunt obstruction
- Guillain-Barre syndrome
- Certain tumours
- Drugs
What CNS system disorders can cause SIADH?
- Meningitis
- Encephalitis
- Trauma
- Hypoxia
What respiratory conditions can cause SIADH?
- Pneumonia
- TB
What tumours can cause SIADH?
- Thymoma
- Lymphoma
- Ewing’s sarcoma
What does SIADH result in?
- Impaired free water clearance
- Total body water excess
- Hyponatraemia
How is SIADH managed?
- Treatment of underlying cause
- Fluid restriction when mild and asymptomatic
- When more severe, use of democycline
How does democycline work in SIADH?
It inhibits the action of vasopressin on its receptor
What is the limitation of the use of democycline in paediatrics?
It has yet to be tested and licensed for use in children
