1b// Pituitary Tomours

Question 1

What are the anterior pituitary cells and their hormones?

Answer 1

Somatotrophs= Growth Hormone (somatotrophin)

Lactotrophs= Prolactin

Thyrotrophs= Thyroid stimulating hormone (TSH) (thyrotrophin)

Gonadotrophs= luteinising hormone and follicle stimulating hormone (LH and FSH)

Corticotrophs= Adrenocorticotrophic hormone (ACTH, corticotrophin)

Question 2

What happens with functioning tumours of the anterior pituitary?

Answer 2

somatotrophs= acromegaly

lactotrophs= prolactinoma

thyrotrophs= TSHoma

gonadotrophs= gonadotrophinoma

corticotrophs= cushing’s disease (corticotroph adenoma)

Question 3

What categories can you categorise pituitary tumours in?

Answer 3

Radiological (MRI)…

* Size 
- Microadenoma <1cm 
- Macroadenoma >1cm
* Sellar or suprasellar
* Compressing optic chiasm or not
* Invading cavernous sinus or not 

Function…

* Excess secretion of a specific pituitary hormone
- E.g., prolactinoma
* No excess secretion of pituitary hormone (non-functioning adenoma) 

Benign or malignant…

* Pituitary carcinoma very rare (<0.5% of pituitary tumours)
* Mitotic index measured using ki67 index- benign is <3% Pituitary adenomas can have benign histology but display malignant behaviour

Question 4

What does hyperprolactinaemia cause?

Answer 4

inhibits kisspeptin neurones

Question 5

How are kisspeptin neurones inhibited and what does it cause?

Answer 5

1) prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus

2) inhibits kisspeptin release

3) decreases in downstream GnRH/ LH/ FSH/ T/ Oest

4) oligo-amenorrhoea/ low libido/ infertility/ osteoporosis

Question 6

What is the commonest functioning pituitary adenoma?

Answer 6

prolactinomas

Question 7

what is the serum concentration of prolactin proportional to with a prolactinoma?

Answer 7

tumour size

Question 8

What are the symptoms of prolactinomas?

Answer 8

menstrual disturbance
erectile dysfunction
reduced libido
galactorrhoea
subfertility

Question 9

What are other physiological causes of an elevated prolactin?

Answer 9

pregnancy/ breastfeeding

stress: exercise, seizure, venepuncture

nipple/ chest wall stimulation

Question 10

What are other pathological causes of an elevated prolactin?

Answer 10

primary hypothyroidism

polycystic ovarian syndrome

chronic renal failure

Question 11

What are other latrogenic causes of an elevated prolactin?

Answer 11

antipsychotics

selective serotonin re-uptake inhibitors

anti-emetics

high dose oestrogen

opiates

Question 12

What should you do once you’ve confirmed the true pathological elevation of serum prolactin?

Answer 12

pituitary MRI

Question 13

How do you treat prolactinomas?

Answer 13

• First-line treatment is medical not surgical
• Dopamine receptor agonists mainstay of
  treatment
• Cabergoline (bromocriptine)
• Safe in pregnancy
• Aim is to normalise serum prolactin & shrink prolactinoma
• Microprolactinomas will need smaller doses than macroprolactinomas

Question 14

How do dopamine receptor agonists work?

Answer 14

1) normally, anterior pituitary lactotrophs secrete prolactin
- they have D2 receptors (for dopamine)
- dopamine from hypothalamic dopaminergic neurones binds to D2 receptors and stops prolactin secretion

2) D2 (dopamine) receptor agonists bind to the D2 receptors and stop prolactin secretion

Question 15

What does excess GH cause?

Answer 15

acromegaly in adults
gigantism in children

Question 16

What are symptoms of acromegaly? (10)

Answer 16

• Sweatiness
• Headache
• Coarsening of facial features
• Macroglossia
• Prominent nose
• Large jaw - prognathism
• Increased hand and feet size
• Snoring & obstructive sleep apnoea
• Hypertension
• Impaired glucose tolerance/diabetes mellitus

Question 17

What is the average time of diagnosis from start of symptoms for acromegaly and why?

Answer 17

Often insidious presentation – mean time to diagnosis from onset of symptoms = 10y

Question 18

What is the mechanism for GH?

Answer 18

Question 19

How can you diagnose acromegaly?

Answer 19

Gh is pulsatile- so random measurements are unhelpful

Elevated of serum IGF-1

Failed suppression (paradoxical rise) of GH following oral glucose load- oral glucose tolerance test

Once confirm GH excess, pituitary MRI to visualise pituitary tumour

Question 20

What is the first line treatment for acromegaly?

Answer 20

surgical- trans-sphenoidal pituitary surgery

Question 21

What risk is increased with untreated acromegaly?

Answer 21

increased cardiovascular risk

Question 22

What is the aim for treatment for acromegaly?

Answer 22

normalise GH and IGF-1

Question 23

What is the purpose of medical treatment for acromegaly?

Answer 23

Can use medical treatment prior to surgery to shrink tumour or if surgical resection incomplete

Somatostatin analogues eg octreotide –
‘endocrine cyanide’

Dopamine agonists eg cabergoline (GH secreting pituitary tumours frequently express D2 receptors)

Question 24

What is a treatment for acromegaly but is slow?

Answer 24

radiotherapy

Question 25

What is cushing’s syndrome?

Answer 25

excess cortisol

Question 26

What causes cushing’s syndrome?

Answer 26

due to a pituitary corticotroph adenoma secreting ACTH

Question 27

What are symptoms of cushing’s syndrome?

Answer 27

mental changes (depression)
osteoporosis
impaired glucose tolerance (diabetes)
high blood pressure
proximal myopathy (muscle weakness) (thin arms and legs)
easy bruising
moon face
red cheeks
fat pads
thin skin
purple striae
pendulous abdomen
poor wound healing

Question 28

How do you investigate cushing’s syndrome?

Answer 28

Question 29

What is cushing’s disease dependent on?

Answer 29

ACTH

Question 30

Give 2 examples of ACTH dependent and independent reasons for hypercortisolism?

Answer 30

ACTH dependent…
- Cushing’s disease (pituitary corticotroph adenoma)
- ectopic ACTH (e.g., lung cancer)

ACTH independent…
- taking steroids by mouth
- adrenal adenoma or carcinoma

Question 31

What should you do once confirmed hypercortisolism?

Answer 31

measure ACTH, if ACTH Is high do a pituitary tumour

Question 32

What can non-functioning pituitary adenomas do to vision?

Answer 32

they don’t secrete any hormone

bitemporal hemianopia

Question 33

What can non-functioning pituitary adenomas present with to do with hormones?

Answer 33

hypopituitarism

serum prolactin can be raised (dopamine can’t travel down pituitary stalk from hypothalamus)

Question 34

How do you treat non-functioning pituitary tumours that cause disturbances?

Answer 34

trans-sphenoidal surgery needed for larger tumours, particularly is visual disturbance