Pituitary Tumours

Question 1

What do somatotrophs produce?

Answer 1

Growth Hormone / somatotrophin

Question 2

What do lactotrophs produce?

Answer 2

Prolactin

Question 3

What do thyrotrophs produce?

Answer 3

Thyroid stimulating hormone (TSH/thyrotrophin)

Question 4

What do gonadotrophs produce?

Answer 4

Luteinising hormone (LH)
Follicile stimulating hormone (FSH)

Question 5

What do corticotrophs produce?

Answer 5

Adrenocorticotrophic hormone

ACTH/corticotrophin

Question 6

What does a tumour affecting somatotrophs result in?

Answer 6

Acromegaly (adults)

Gigantism (children)

Question 7

What does a tumour affecting lactotrophs result in?

Answer 7

Prolactinoma

Question 8

What does a tumour affecting thyrotrophs result in?

Answer 8

TSHoma

Question 9

What does a tumour affecting gonadotrophs result in?

Answer 9

Gonadotrophinoma

Question 10

What does a tumour affecting corticotrophs result in?

Answer 10

Cushing’s disease (corticotrophasdenoma)

Question 11

How is a pituitary tumour classified from an MRI?

Answer 11

• Size:
  < 1cm : microadenoma
  > 1cm : macroadenoma
• Location (suprasellar or sellar)
• Whether it is compressing the optic chiasm
• Whether it is invading the cavernous sinus

Question 12

How is a pituitary tumour classed based on it’s function?

Answer 12

• excess secretion of a pituitary hormone
• no excess secretion, therefore a: non-functioning adenoma

Question 13

How is a pituitary tumour classed as either benign or malignant?

Answer 13

• (carcinomas are very rare, < 0.5%)
• Using the mitotic index (Ki67 index), with benign being < 3%
• It is possible for pituitary adenomas to have a benign histology but display malignant behaviour

Question 14

How does hyperprolactinaemia inhibit kisspeptin neurons?

Answer 14

• prolactin binds to prolactin receptors on kisspeptin neurons in the hypothalamus
• inhibits kisspeptin release
• decreases in downstream GnRH >LH/FSH > T/Oest
• leads to oligo-amenorrhoea/low libido/infertility/osteoporosis

Question 15

Describe prolactinomas?

Answer 15

• Most common functioning pituitary tumour
• serum prolactin >5000mU/L
  (proportional to the size of the tumour)

Question 16

How to prolactinomas present?

Answer 16

• menstrual disturbance
• erectile dysfunction
• reduced libido
• galactorrhoea
• subfertility

Question 17

What are other possible causes of elevated prolactin levels?

Answer 17

• pregnency/breastfeeding
• stress: exercise, seizure, venepuncture
• nipple/chest wall stimulation
• primary hypothyroidism
• PCOS
• chronic renal failure
• antipsychotics
• SSRIs
• Anti-emetics
• High dose oestrogen
• Opiates

Question 18

Why is it necessary to confirm a ‘true’ elevation in serum prolactin?

Answer 18

The stress of a venepuncture can present as an elevation of prolactin (which is false), therefore an alternative method is needed to confirm

Question 19

How to reduce the effect of the stress of venepuncture on prolactin measurements?

Answer 19

• Exclude using a cannulated prolactin series
• sequential serum prolactin measurements 20 minutes apart with an indwelling canulla to minimise stress.

Question 20

How to diagnose a prolactinoma?

Answer 20

• confirm an elevated level of serum prolactin
• a pituitary MRI

Question 21

How to treat a prolactinoma?

Answer 21

Medical (first line)

• dopamine receptor agonists
• cabergoline (bromocriptine)
• safe during pregnancy
• dosage depends on size of the prolactinoma (micro = smaller dose)
• Aim: normalise serum prolactin and shrink the prolactinoma.

Question 22

How do dopamine receptor agonists work?

Answer 22

They bind to D2 receptors on anterior pituitary lactotrophs to inhibit the release of prolactin

works in the same way as somatic dopamine

Question 23

How does acromegaly present?

Answer 23

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

Question 24

How to diagnose acromegaly?

Answer 24

• elevated serum IGF-1
• Failed suppression (‘paradoxical rise’) of GH following oral glucose load
  (oral glucose tolerance test)
• Raised prolactin (due to co-secretion)
• Once GH excess confirmed, Pituitary MRI.

Question 25

How to treat acromegaly?

Answer 25

Surgery (First Line)
- trans-sphenoidal pituitary surgery
Aim: normalise serum GH and IGF-1
Medication (Second Line)
(shrink pre-surgery or if surgical resection is incomplete)
- somatostatin analogues 
eg: octreotide 'endocrine cyanide'
- dopamine agonists 
eg: cabergoline
(GH pituitary tumours often express D2 receptors)
Radiotherapy (slow)

Question 26

What causes Cushing’s syndrome?

Answer 26

excess cortisol (or other glucocorticoid)
ACTH-dependent:
- Cushing's disease (corticotrophadenoma)
- Ectopic ACTH
(lung cancer)
ACTH-Independent
- oral steroids (common)
- adrenal adenoma or carcinoma

Question 27

What is Cushing’s disease?

Answer 27

Excess ACTH due to a corticotrophadenoma

Question 28

How to diagnose Cushing’s Disease?

Answer 28

• elevation of 24hr urine free cortisol - increased secretion
• elevation of late night cortisol (salivary or blood test) - loss of diurnal rhythm
• failure to supress cortisol after oral dexamethasone
  (exogenous glucocorticoid) - increased cortisol secretion
  Once confirmed hypercortisolism, measure ACTH.
  If high, pituitary MRI

Question 29

How do non-functioning pituitary adenomas present?

Answer 29

• no specific hormone secretion
• often cause visual disturbance
  (bitemporal hemianopia)
• occasional hypopituitarism
• elevated serum prolactin (dopamine can’t travel down the pituitary stalk)

Question 30

How to treat visual disturbance caused by non-functioning adenomas?

Answer 30

Trans-sphenoidal surgery

also can be used if the tumour is large

Question 31

What is the mechanism of growth hormone action?

Answer 31

• stimulates metanolic actions in body tissues leading to growth and development
• stimulates IGF-1 (and IGF-2) secretion from the liver which has the same action as GH

Question 32

What is increased in untreatead acromegaly?

Answer 32

Cardiovascular risk