7.02 - Pituitary Tumour

Front 1

Three parts of the anterior pituitary?

Back 1

Pars distalis (the main part, makes the hormones)
Pars tuberalis
Pars intermedia (between the post and ant pituitaries)

Front 2

Two parts of the posterior pituitary?

Back 2

Pars nervosa
infundibulum

Front 3

What bone does the pituitary fossa sit in?

Back 3

Sphenoid bone

Front 4

Where does the pituitary fossa sit relative to the sphenoidal sinus?

Back 4

Pit fossa is superior to the sphenoidal sinus

Front 5

What forms the roof of the pituitary fossa?

Back 5

Sellar diaphragm
= sheet of dura stretching between the two clinoid processes

Front 6

What's anterior to the pituitary fossa?

Back 6

Optic chaism

Front 7

What's anterior and slightly lateral to the pituitary fossa?

Back 7

Internal carotid arteries

Front 8

What is located lateral to the pituitary fossa?

Back 8

The cavernous sinus

Front 9

What travels in the walls of the cavernous sinus?

Back 9

III
IV
V1

Front 10

What travels in the floor of the cavernous sinus?

Back 10

V2

Front 11

What travels through the cavernous sinus itself?

Back 11

ICA + associated carotid plexus
CN VI

Front 12

Where do the neurohypophysis originate from embryologically

Back 12

The floor of the diencephalon

Front 13

Where does the adenohypophysis originate from embryologically?

Back 13

The roof of the mouth (pharynx)

Front 14

What's the name of the part of the pituitary that sits between the bulk of the ant pit and the posterior pit?

Back 14

Pars intermedia (it's actually technically part of the ant pit)

Front 15

Acidophils in ant pit produce what hormones?

Back 15

Prolactin (from lactotropes)
Growth hormone (from somatotropes)

Front 16

What's the name of the cells that produce GH?

Back 16

Somatotropes

Front 17

What does prolactin do in males?

Back 17

Raises testosterone binding in the prostate
And increases formation of androgen - R complexes

Front 18

What cell types are the basophils in the ant pit and what do they produce?

Back 18

B-FLAT
FSH and LH -> gonadotropes
ACTH -> adrenocorticotropes
TSH -> thryrotropes

Front 19

Are the nerves in the post pit myelinated or not?

Back 19

unmyelinated

Front 20

What are the two hypothalamic nuclei from which post pit neurons originate?

Back 20

Supra optic nucleus (SON)
Paraventricular nucleus (PVN)

Front 21

What do axons coming from the medial eminence do?

Back 21

They release inhibiting agents that control the levels of all hormones in the adenohypophysis

Front 22

What are the BVs supplying the pituitary gland?
what do they each supply?

Back 22

Several superior hypophyseal arteries (-> supply the infundibulum and thence portal circulation) and a single inferior hypophyseal artery (supplies the neural lobe)
They're all branches off the IA

Front 23

What % of subjects at autopsy will have pituitary tumours?

Back 23

6-23%

Front 24

What % of 'normal' pituitary glands show a lesion of 3mm+ on CT / MRI?

Back 24

20%

Front 25

Do pit tumours regularly metastasise?

Back 25

NO

Front 26

What is a micro and macro adenoma?

Back 26

Micro - less than 1cm
Macro - more than 1cm

Front 27

What are some of the local mass effects you can get with a macroadenoma?

Back 27

- Headache (due to stretching of the dura mater)
- CSF obstruction and hydrocephalus (if tumour is really large)
- Visual field defects due to compression of optic chiasm (bitemporal hemianopia)
- III, IV or VI CN palsies
- CSF rhinorrhea from erosion of the sella turcica

Front 28

If something is knocking out your pituitary hormones, which are usually the first to go? And then what's the order from there down?

Back 28

Gonadotropins - LH and FSH
Then GH
Then TSH
Last = ACTH

Front 29

What does a craniopharyngeoma originate from?

Back 29

Rathke's pouch = the diverticulum at the roof of teh mouth that usually gives rise to the ant pit
IE congenital malformation

Front 30

What age gp usually present with craniopharyngiomas? And what's the most common presenting complaint?

Back 30

Middle childhood
They usually present with complaints related to increased ICP -> triad: headaches, vomiting papilloedema

Front 31

What sort of cells make up a craniopharyngeoma?

Back 31

Squamous cells

Front 32

What is the most common type of pituitary tumour?

Back 32

Non-functioning adenoma (they secrete nothing OR they secrete biologically inactive subunits eg subunit)

Front 33

List from most common to least common the pituitary tumours we get

Back 33

1. non functioning adenoma (32%)
2. Prolactinoma (27%)
3. GH producing adenoma (13%)
4. Corticotrope adenoma
5. Gonadotrope adenoma
6. Combine GH and prolactin producing adenoma
7. Thyrotrope adenoma (1% ie very rare!)

Front 34

Prolactinoma in women - most commonly micro or macro adenomas?

Back 34

MICRO

Front 35

Prolactinoma -> what symptoms would you see in womena dn in men?

Back 35

Women: galactorrhea, menstrual irregularity (suppresses FSH and LH) or infertility
Men: sexual dysfunction

Front 36

GH secreting adenoma -> what do you see?

Back 36

Children -> gigantism (before plates have fused)
Adult -> acromegaly

Front 37

Corticotrope producing adenoma -> what do you see?

Back 37

cushin's

Front 38

Gonadotrope producing adenoma -> what do you see?

Back 38

Women don't have any symptoms
Men -> gynacomastia and sexual dysfunction
Kids -> precocious puberty

Front 39

Intracranial P depends on three components - what are they?

Back 39

Brain
CSF
Blood

Front 40

Children -> more or less tolerant of visual disturbances?

Back 40

more tolerant

Front 41

Most common mode of presentation of craniopharyngioma in kids?

Back 41

Symptoms of raised ICP (vom, headaches, papilloedema)

Front 42

What causes the headache you get in ICP?

Back 42

Tension or pain sensitive structures in the dura, or BVs
(brain itself has no sensory supply)

Front 43

Headache with raised ICP worst when?

Back 43

First thing in the morning

Front 44

Why do you get vomiting with raised ICP?
More common in kids or adults?
Proceeded by nausea?

Back 44

Distortion or ischaemia of areas in the med involved in vomiting
More common in kids
Not proceeded by nausea

Front 45

Why do you get papilloedema with raised ICP?

Back 45

The pressure is transmitted along teh optic nerve sheath -> get swelling and venous congestion of teh optic nerve head

Front 46

Someone doesn't have papilloedema -> can you rule out raised ICP ?

Back 46

No. It is pathognomonic - if you see it, very very likely they have raised ICP. But no papilloedema does not = no raised ICP

Front 47

Why do some people not get papilloedema with raised ICP?

Back 47

Anat of nerve sheath may not allow the transmission of pressure
If they've had high ICP before, might have fibrosis of the sheath

Front 48

What are the four phases of childhood growth?

Back 48

Prenatal
Infantile
Childhood
Pubertal growth spurt

Front 49

prenatal growth -> how many cms?

Back 49

50cm in 9 months (approx)

Front 50

Does fetal growth depend on fetal and maternal hormones?

Back 50

No!
depends on nutrition, quality of placenta, toxins, maternal health, intra uterine factors and genetic factors

Front 51

What is postnatal growth in cm ?

Back 51

Approx 114 in females and 127 in males
(=in addition to the 50cm they grew in the womb)

Front 52

Infantile phase of growth -> accelerating or decelerating?

Back 52

Rapidly decelerating

Front 53

In the three phases of growth after baby is born, what factors are impt in each phase?

Back 53

Infantile - depends on nutrition and genetic factors. Endocrine hormones have a contributory role
Childhood growth - genetic factors and growth hormone
Pubertal growth spurt - sex steroids and GH

Front 54

How many cms do females and males gain in the pubertal growth spurt

Back 54

females - 25cm
males - 28cm

Front 55

Is there difference in height growth between the sexes before puberty?

Back 55

NO

Front 56

Why do boys end up taller than girls (post-puberty)? 2 reasons

Back 56

1. they enter puberty about 2 years later
2. They grow 3cm more in teh pubertal growth spurt

Front 57

Variabilty between diff peoples heights = due to what?

Back 57

Mostly genes

Front 58

GH is released tonically or in pulsatile manner?

Back 58

pulsatile

Front 59

What % of linear growth and weight accummulation is achieved in utero?

Back 59

Get 30% of total linear growth
Only 5% of weight gain

Front 60

What's weight at one year in terms of birth weight?

Back 60

3 times higher !

Front 61

During puberty, what changes do we see starting to emerge in body composition?

Back 61

Females - increase in body fat
Males - increase in lean tissue mass
Peak bone mass achieved within a few years of completing pubertal growth spurt

Front 62

Where's the 'biological clock'?

Back 62

SCN (supra-chaismatic nucleus) in anterior hypothal

Front 63

What's the pathway by which light info gets into the SCN? Dependent on rods and cones?

Back 63

Retinohypothalamic tract (RHT)

Not dependent on rods and cones

Front 64

Where is melatonin secreted?

Back 64

Pineal gland

Front 65

During the day, what's happening with melatonin secretion?

Back 65

Being inhibited by symp neurons coming from the SCN

Front 66

Melatonin produced during teh day or at night? Does it depend more on light/dark or sleep/awake?

Back 66

NIGHT (in absence of light cues)

Doesn't depend on sleep/wake cycle! Depends on light/dark!

Front 67

What biological marker do we use to work out the 'internal time' in humans?

Back 67

melatonin

Front 68

What's the primary metabolite of melatonin?

Back 68

6-sulphatoxymelatonin
Gets excreted in urine

Front 69

What does peak in melatonin do to wakefulness?

Back 69

Peak melatonin -> peak sleepiness

Front 70

what happens if you administer melatonin to someone?

Back 70

(remember, highest at night ie promotes sleepfulness)
-> IV dose will make them sleepy and decrease alertness and cognitive performance

Front 71

When does cortisol peak? What happens if sleep offset is delayed?

Back 71

Peaks early in the morning. If offset of sleep (waking up) is delayed, so is the peak of cortisol

Front 72

24 hour sleep deprivation -> what happens to your cortisol levels?

Back 72

They tend to be elevated compared to normal 24 hour levels (because you don't go to sleep -> can't dip down like normally would)

Front 73

What is a herring body? Where are they found?

Back 73

Big swelling at the end of an axon = where the axon is synapsing with a blood vessel
in posterior pituitary

Front 74

Looking at a histological section -> how do you tell the difference between pars distalis and pars nervosa?

Back 74

Distalis -> way more cell bodies --> darker staining

Front 75

Neurohypophysis is supplied by which BV?

Back 75

inf hypophysial artery

Front 76

Adenohypophysis is supplied by which BV?

Back 76

superior hypophysial artery

Front 77

What are the main cell type in the anterior pit?

Back 77

Somatotrophs
make up 40-50%

Front 78

What does the pars intermedia look like on histological stain? What does this area produce?

Back 78

Like thyroid gland because have follicle cells surrounding central area
Produces endorphins and MSH

Front 79

What's the name of the specialised glial cells in the posterior pituitary?

Back 79

Pituicytes

Front 80

If you see Herring bodies, what part of teh body are you looking at?

Back 80

Posterior pituitary

Front 81

What are the two cell types in the thyroid gland? And what do they each produce?

Back 81

- Follicular cells - produce TH into the colloid
- Parafollicular cells - don't come in contact with colloid. Produce calcitonin (decreases blood ca2+)

Front 82

T/F: follicular cells have lots of micro-villi?

Back 82

TRUE

Front 83

What sort of ep cells surround the thyroid follicle?

Back 83

Cuboidal
They have lots of microvilli

Front 84

What two cell types do we have in the parathyroid gland?

Back 84

- Oxyphil cells - large. We don't really know what they do / secrete
- Chief cells - smaller - thyey make the PTH. Have lots of glycogen lipid droplets in their cytoplasm

Front 85

What are the three layers of the adrenal gland? What do they each produce?

Back 85

Remember GFR
Zona glomerulosa --> aldosterone
Zona fasciculata --> glucocorticoids
Zona reticularis --> androgens

Front 86

What's the big hole you see in the middle of the adrenal medulla?

Back 86

Central medullary vein

Front 87

What are the three types of cells we have in the medulla?

Back 87

- Pre synaptic nerve fibres (unmyelinated)
- Chromaffin cells - produce catecholamines
- Ganglion cells - moderate secretions of the chromaffin cells

Front 88

What cell types do we have in the zona glomerulosa and how are they arranged?

Back 88

Columnar cells
Arranged in clusters and cords

Front 89

What cell types do we have in the zona fasciculata and how are they arranged?

Back 89

Polyhedral cells
Arranged in straight cords

Front 90

What's syntocinon?

Back 90

Synthetic oxytocin - used to induce labour or induce ejection of the placenta after birth

Front 91

What's atosibar?

Back 91

oxytocin antagonist used to prevent premature birth

Front 92

What are the big two classical functions of oxytocin?

Back 92

Parturition
Lactation

Front 93

what's the effect of GH?

Back 93

Tissues -> increased protein synthesis -> growth (anabolism)
Liver -> synthesis of IGF-1 -> bone cartilage and soft tissue growth
GH also increases blood gluc conc (decreases uptake into cells)

Front 94

What happens to GH levels when you have high blood glucose?

Back 94

high blood gluc -> increased somatostatin -> decreased GH

Front 95

Why do women get disturbed menstrual cycle with hyperprolactinemia/

Back 95

High prolactin suppresses GnRH -> decreased FSH and LH -> don't get normal cycles
= functional gonadotrophin deficiency

Front 96

If we suspect someone is lacking a hormone, what sort of test would we do?

Back 96

Stimulation test

Front 97

If we suspect someone has excess hormone, what sort of test would we do?

Back 97

Suppression test

Front 98

What's the difference between problems that parents / doctors report about short kids cf what formal testing shows?

Back 98

Parents / doctors rate the child as having more problems than formal testing might show

Front 99

Vasopressin - what are the two Rs it can act on and what response is elicited by each? And what's the secondary messenger molecule in each?

Back 99

V1 = on vascular smooth muscle cells -> increased vasoconstriction. cAMP is messenger
V2 = on the kidney -> increased insertion of aquaporins -> increased H20 reabsorption. DAG/IP3 is the messenger

Front 100

What's the most potent stimulus for vasopressin release? Give details

Back 100

increased osmolarity (ion conc)
Threshold for secretion = 280mosm/L. Normal osmolarity = 290

Front 101

If we have really low BP, vasopressin kicks in and helps out. What is the process by which it is released in this situation?

Back 101

Baro Rs in the carotid sinus and aortic arch - when P is low they tell the SON and PVN in hypothal to increase vasopressin release

Front 102

What's the difference in VP levels in dehydration (high osmolarity) and very low BP?

Back 102

Max VP conc with high osmolarity is 10 times LOWER than what you get with low BP

Front 103

What's nicotine's effect on VP release?

Back 103

Inhibits it

Front 104

What happens in diabetes insipidus?

Back 104

Have lots of tasteless urine
Destruction of cell bodies in hypothal or mutation in VP gene -> don't get the aquaporins being inserted in response to increased osmolarity -> always have lots of H20 in teh urine -> very thirsty as well because you'll be dehydrated
If the thirst mechanism is disrupted, you'll get circulatory collapse and die.

Front 105

What's the treatment for diabetes insipidus?

Back 105

Nasal vasopressin

Front 106

What are the two main actions of oxytocin? And two other less impt ones mentioned by learning topics?

Back 106

- Uterine contractions
- Milk secretion
- Sex -> increased secretion -> uterine contractions help to propel semen into fallopian tubes
- Behavioural effects

Front 107

what are the two big classes of cell type that pit tumours can arise from? Which are more common in kids? which in adults?

Back 107

- Primary pit tumours = adenohypophyseal origin - more common in adults
- Tumours of germ cell origin - more common in kids

Front 108

Are craniopharyngeomas functioning?

Back 108

NO!

Front 109

What % of sellar region tumour in kids are craniopharyngeomas?

Back 109

50%

Front 110

Adults with pituitary tumour - usually present with what kind of problems?

Back 110

Those due to an endocrinopathy

Front 111

How do you surgically access pituitary tumours?

Back 111

Trans-sphenoidal microsurgery

Front 112

In what pit tumour patients would we use radiotherapy?

Back 112

If the tumour wasn't completely removed with surgery and/or it's recurred
Or in unusual patients who can't have surgery / medical options for whatever reasons

Front 113

What drug can we use with prolactinomas?

Back 113

Cabergoline = dopamine agonist -> puts the breaks on prolactin synthesis and release

Front 114

What drug can we use with GH secreting tumours?

Back 114

Octreotide = analogue of somatostatin -> will decrease the GH levels and size of the tumour

Front 115

HAVEN'T DONE CARDS ON LECTURE 4 (ant pit hormones) and LECTURE 5 (post pit hormones)

Back 115

==> REVISE THESE LECTURES

Front 116

MC1R located where?

Back 116

Melanocytes

Front 117

MC2R located where?

Back 117

Adrenal cortex
adipocytes

Front 118

MC3R and MC4R located where?

Back 118

Brain (hypothalamus)

Front 119

MC5R located where?

Back 119

Sebaceous glands

Front 120

What's the effect of a lesion in the medial ventromedial nucleus?

Back 120

Increased eating -> obese

Front 121

What's the effect of a lesion in the lateral ventromedial nucleus?

Back 121

Weight loss

Front 122

Describe Prader Willi Syndrome

Back 122

Due to deletion on their chrom 15 (on paternal copy) - and the maternal copy of this region is normally silenced --> have no functional genes acting!
Occurs in 1/10,000 - 1/25,000 live births
==> Obese, hyperphagia, absent satiety, intellectual disability, GH deficient -> they're short, hypotonia + weak muscles, hypogonadism etc etc

Front 123

What is Bardet Biedl syndrome?

Back 123

Autosomal recessive
Have hypothalamus problems
Intellectual disability, early onset obesity, pigmentary retinopathy, hypogonadism, polydactylyl, renal problems

Front 124

What's the mechanism underlying cachexia in cancer?

Back 124

Increased production of cytokines -> they act on cytokine - Rs in the hypothalamus -> Get disruption of the normal feeding response to under-nutrition

Front 125

ob/ob mouse - has what? What problems do we see in these mice?

Back 125

Leptin deficiency
=> OBESE + hypothyroid, hypogonadism, hyperinsulinaemia, T-cell dysfunction

Front 126

db/db mouse has what?

Back 126

Leptin resistance

Front 127

Are levels of leptin higher in men or women on average?

Back 127

Women (because they have more fat usually)

Front 128

What is the role of leptin?

Back 128

Decreases food intake and increases energy expenditure

Front 129

What's the structure of leptin?

Back 129

peptide

Front 130

Describe the actions of leptin

Back 130

It inhibits neuropeptide Y and AGRP neurons in the arcuate nucleus --> decreased eating
And stimulates alpha-MSH neurons + CART neurons
--> increased feeling of satiety

Front 131

What is neuropeptide Y?

Back 131

Peptide produced by neurons mostly in teh arcuate nucleus. It stimulates feeding and decreases energy expenditure -> makes you fat

Front 132

What is AGRP?

Back 132

Agouti related peptide
Makes you fat

Front 133

What does alpha-MSH originate from? How do we get it?

Back 133

Comes from POMC -> converted to alpha-MSH by pro-hormone convertase 2 (PC2)

Front 134

Does CART increase or decrease food intake?

Back 134

Decreases (it increases satiety

Front 135

Does alpha MSH increase or decrease food intake?

Back 135

Decreases

Front 136

Does neuropeptide Y increase or decrease food intake?

Back 136

Increases

Front 137

Does AGRP increase or decrease food intake?

Back 137

Increases

Front 138

What is gherelin?

Back 138

It's a gut hormone - produced when the gut is empty -> increases our appetite
It's a GH secretagogue (ie -> GH secretion)

Front 139

Are gherelin levels high or low before a meal?

Back 139

HIgh

Front 140

Are gherelin levels high or low when you're losing weight?

Back 140

High

Front 141

Does gherelin increase or decrease food intake?

Back 141

Increases

Front 142

What does orexigenic mean?

Back 142

Increases your appetite

Front 143

What does anorexigenic mean?

Back 143

Decreases your appetite

Front 144

What are the gut hormones that decrease your food intake?

Back 144

CCK (=cholecystokin)
GLP-1
PYY

Front 145

Does CCK increase or decrease food intake?

Back 145

Decreases - it's increased during meal -> involved in meal termination

Front 146

Does orexin increase or decrease food intake? What stimulates its production

Back 146

Increases
Production is stimulated by decreased glucose levels

Front 147

Describe congenital leptin deficiency

Back 147

First monogenic cause of obesity identified. Very rare. Only 12 identified cases in the world!
Get hyperphagia, insatiable appetite, obesity. Reproductive and immunological abnormalities as well. Normal growth
Can be treated with daily injections of leptin

Front 148

Describe congenital leptin receptor deficiency

Back 148

Slightly more common than leptin deficiency. Not as severe - presumably the leptin is working elsewhere as well
Will have increased leptin levels in the blood (due to feedback)
Normal linear growth but delayed puberty (due to secondary hypogonadism) adn don't properly go through puberty -> don't get normal growth spurt -> decreased final high
Prevalance was about 3% in the severely obese cohort

Front 149

What's the most common monogenic cause of obesity that we've identified?

Back 149

Melanocortin 4 R deficiency
Prevalence = about 6% of severely obese patients

Front 150

Describe what happens if you have congenital POMC deficiency

Back 150

No POMC -> won't get alpha-MSH -> don't get the appetite suppression from it -> Obese
In addition, don't have ACTH -> don't get cortisol --> adrenal crises
Lack melanin -> red hair white skin
Can't convert pro-hormones to their actual hormones -> build up of the pro-hormones (pro-insulin, glucagon and gastrin)

Front 151

Where is POMC produced?

Back 151

Corticotrophs (cells in ant pit that produce ACTH)

Front 152

DIDN'T DO LECTURE SIX - PUBERTY

Back 152

STUDY IT

Front 153

DIDN'T DO LECTURE 7 - REPLACEMENT THERAPY FOR HORMONAL DEFICIENCIES

Back 153

STUDY IT

Front 154

ANATOMY LECTURE (DEB B) NOT COVERED

Back 154

STUDY IT

Front 155

HISTOLOGY ONLY DONE VERY BRIEFLY

Back 155

SHOULD READ THROUGH IT AGAIN