Lecture 13: Pituitary

Question 1

Where is the pituitary gland located

Answer 1

The pituitary gland is located in the brain, between the hypothalamus and the pineal gland, just behind the bridge of the nose. It is about the size of a pea and is attached to the brain by a thin stem of blood vessels and nerve cell projections.

Question 2

The hypothalamus is connected to the anterior pituitary by what

Answer 2

Hypophyseal portal system: network of capillary that connect the hypothalamus and anterior pituitary

Question 3

The hypophyseal portal system connects the hypothalamus to the _____ pituitary

Answer 3

Anterior

Question 4

The hypothalamus is connected to the posterior pituitary by what

Answer 4

By the hypothalamic hypophyseal tract (i.e. nerves extend down)

Thus, the posterior pituitary is a direct extension of the CNS

Question 5

The hypothalamic hypophyseal tract connects the hypothalamus to the _____ pituitary

Answer 5

Posterior

Question 6

The pituitary gland sits within a small depression in the ____ bone

Answer 6

It sits within a small depression in the sphenoid bone

Question 7

Name the hormones released by the anterior pituitary

Answer 7

1. Growth hormone (GH)
2. Thyroid stimulating hormone (TSH)
3. Follicle stimulating hormone (FSH)
4. Luteinising hormone (LH)
5. Adrenocorticotrophic hormone (ACTH)
6. Prolactin (PRL)

Question 8

Name the hormones released by the posterior pituitary

Answer 8

1. Antidiuretic hormone (ADH)
2. Oxytocin

Question 9

Fill in the blanks regarding the hormones each side of the pituitary produces

Answer 9

Question 10

Describe the Growth hormone (Somatotroph) axis

Answer 10

• GH secretion is pulsatile, mainly overnight
• Multiple physiological effects- mostly in childhood
• Growth hormone either direct effects tissues or;
• Stimulates the production of insulin-like growth factor-1 (IGF-1) from liver and has effects indirectly.
• Both IGF-1 and GH acts as a negative feedback- inhibiting the anterior pituitary and hypothalamus

Question 11

Name a condition that is due to underproduction of growth hormone (i.e. low growth hormone)

Answer 11

Pituitary dwarfism

Question 12

Name a condition that is due to overproduction of growth hormone (i.e. low growth hormone)

Answer 12

Acromegaly is caused by the pituitary gland overproducing growth hormone

Question 13

Describe the Hypothalamic-pituitary-adrenal axis

Answer 13

Question 14

Describe the Hypothalamic-pituitary-thyroid axis

Answer 14

Question 15

Describe the Lactotroph axis

Answer 15

Question 16

The hypothalamus releases ____ which ______ the anterior pituitary to release prolactin

Answer 16

A) Dopamine

B) Inhibitory

Question 17

Neurohypophysis refers to which structure?

Answer 17

Posterior pituitary

Question 18

What are the hormones released by the posterior pituitary

Answer 18

ADH aka vasopressin

Oxytocin

Question 19

Describe the release of oxytocin during suckling

Answer 19

In lactating mothers, oxytocin acts at the mammary glands, causing milk to be ‘let down’ into subareolar sinuses, from where it can be excreted via the nipple.

Suckling by the infant at the nipple is relayed by spinal nerves to the hypothalamus. The stimulation causes neurons that make oxytocin to fire action potentials in intermittent bursts; these bursts result in the secretion of pulses of oxytocin from the neurosecretory nerve terminals of the pituitary gland.

Question 20

Name some clinical conditions that is a result of changes in the posterior pituitary

Answer 20

1. Diabetes insipidus (lack of ADH)
2. Syndrome of inappropriate anti-diuretic hormone (too much ADH)

Question 21

What condition causes large volumes of very dilute urine to pass

Answer 21

Diabetes insipidus

Question 22

Describe the mechanism of action of ADH

Answer 22

• The binding of ADH to the V2 vasopressin receptor (V2R) stimulates a Gs-coupled protein that activates adenylyl cyclase, in turn causing production of cAMP to activate protein kinase A (PKA).
• This pathway increases the exocytosis of aquaporin water channel–containing vesicles (AQMCV) and inhibits endocytosis of the vesicles, both resulting in increases in aquaporin 2 (AQ2) channel formation and apical membrane insertion.
• AQ2 channels function in the reabsorption of water.
• This allows an increase in the permeability of water from the collecting duct (CD).
• Increase water reabsorption

Question 23

Somatostatin is produced by which structure and what is its function?

Answer 23

Somatostatin is produced by the hypothalamus

It inhibits the release of growth hormone and thyroid-stimulating hormone (TSH, GH) from the anterior pituitary

It inhibits insulin and glucagon from the pancreas

It decreases the release of most gastrointestinal hormones, and reduces gastric acid and pancreatic secretion.

Question 24

The ADH binds to which aquaporin channel

Answer 24

Aquaporin 2

Question 25

Aquaporin-1 is located in ____ and \_\_\_\_\_\_. Aquaporin-2 is located in \_\_\_\_\_\_.

Answer 25

Aquaporin-1 is located in the **proximal tubules (PT)** and **descending loop of Henle.** Aquaporin-2 is located in the **collecting ducts (CD).**

Question 26

Define diabetes insipidus and describe the clinical features of it

Answer 26

* DI is the passage of large volumes (\>3 L/day) of dilute urine * Clinical features include: * Polyuria, polydipsia, nocturia * Must exclude hyperglycaemia and hypercalcaemia * Nocturia: up during the night to pee

Question 27

Name the two causes of diabetes insipidus

Answer 27

1. Cranial 2. Nephrogenic

Question 28

Describe the cranial cause of diabetes insipidus

Answer 28

* Deficiency of ADH * Can be idiopathic (unknown cause) or genetic (mutation in ADH gene) * Trauma, tumours, infections, inflammatory conditions of the posterior pituitary * Lack of ADH

Question 29

Describe the nephrogenic cause of diabetes insipidus

Answer 29

**•Resistance to ADH** * Genetic (AVPR2 mutation) * Or secondary to drugs (eg lithium), metabolic upset, renal disease ie. cannot respond to ADH but ADH is still present

Question 30

Cranial diabetes insipidus is the ____ of ADH

Answer 30

Deficiency ADH is not produced

Question 31

Cranial diabetes insipidus is the ____ of ADH

Answer 31

Resistance ADH is produced but unable to respond to it

Question 32

Describe the water deprivation test

Answer 32

Used to diagnosis diabetes insipidus ## Footnote Involves depriving the patients of fluid for 8h and measuring plasma and urine osmolality every 2-4h. After the 8 hours the patients are given synthetic ADH and the urine osmolality is measured. In patients with diabetes insipidus irrespective of the cause, they will produce very dilute high volumes of urine. In cranial DI, when you give synthetic ADH they will start to concentrate the urine. In nephrogenic DI, when you give synthetic ADH they **will not** start to concentrate the urine.

Question 33

What is the treatments available for cranial diabetes insipidus

Answer 33

**Synthetic ADH i.e. desmopressin** ## Footnote –Desmopressin (vasopressin/ADH analogue) –Can be given orally/nasal spray/injection –Monitor plasma sodium and osmolality

Question 34

What is the treatments available for nephrogenic diabetes insipidus

Answer 34

Nephrogenic DI is difficult to treat Ideally treat the underlying cause e.g. change from lithium High doses of synthetic ADH

Question 35

Describe the implications of non-functioning pituitary adenomas

Answer 35

* Pituitary adenomas found in 10% of population * Often asymptomatic (‘incidentalomas’) * Need to exclude hormone dysfunction: * Check for hormone excess * Check for hypopituitarism * Need to ensure no effect on visual fields: * Pituitary located just below optic chiasm * Tumour can expand upwards and push on chiasm causing loss of peripheral vision (‘bitemporal hemianopia’) * Tumours can push on the surrounding pituitary tissue causing an interferes with their function

Question 36

When a pituitary tumour compresses the optic chiasm you get loss of which part of your field of vision

Answer 36

Lateral field of vision

Question 37

Name the secretory pituitary adenomas and which is the most common

Answer 37

* Prolactin- ‘**Prolactinomas**’ * **Commonest**; 30% * ACTH- ‘**Cushing’s** **Disease**’ * 20% * Growth hormone - ‘**Acromegaly**’ * 15% * TSH – ‘**TSHomas**’ * Very rare, \< 1%

Question 38

Describe prolactinomas

Answer 38

* Secretory pituitary adenoma * Most common: 30% * Clinical features: * Galactorrhoea- breast lactate in the non-pregnant state * Menstrual disturbance and subfertility in women * Reduced libido/erectile dysfunction in men * Management: * Dopamine agonists (cabergoline) * Surgery if large tumour with visual field effects

Question 39

Define Acromegaly

Answer 39

•Excessive production of GH (and IGF-1) in adults Iin children its called ‘gigantism’

Question 40

Describe the signs and symptoms of acromegaly

Answer 40

* Sweats * Headache * Tiredness * Increase in ring or shoe size * Joint pains * Coarse facial appearance * Visual field loss * Prominent brows and chin

Question 41

What techniques would you use to diagnose acromegaly

Answer 41

* Glucose tolerance test * Hyperglycaemia switches off growth hormone production but in patients with acromegaly still produce GH. * Check IGF-1 level * Better to detect than GH as it has long half life, protein bound * So more useful than plasma GH * Pituitary MRI * Tumour usually large (macroadenoma, \> 1 cm) and often extends into surrounding structures

Question 42

What is the management for acromegaly

Answer 42

* Surgery is the first line management. Will debulk the disease but would hope to be curative * Medical therapy or radiotherapy: often both. * Medical therapy * Before and after surgery * **Somatostatin** analogues to inhibit GH secretion * GH receptor antagonist * Dopamine agonists * Pituitary radiotherapy * To treat residual tumour * Risk of hypopituitarism and long term problems

Question 43

Which axis/axises are effect by hypopituitarism

Answer 43

Can affect single hormonal axis (FSH/LH most commonly) or all hormones (panhypopituitarism)

Question 44

Define panhypopituitarism

Answer 44

Hypopituitarism affects all the hormones

Question 45

Which hormonal axis do you need to treat first in hypopituitarism

Answer 45

Cortisol!- as it can cause mortality

Question 46

What are the possible causes of hypopituitarism

Answer 46

* **Tumours** - most common (cranial injury or postsurgery) * Radiotherapy * Infarction–if post partum then called Sheehan’s syndrome * Infiltrations (eg sarcoid) –Can affect posterior pituitary too * Trauma * Congenital