Endo - Pituitary Tumour

Question 1

What is the outcome of a functioning somatotrophic tumour?

Answer 1

acromegaly

Question 2

What is a functioning lactotroph tumour called?

Answer 2

prolactinoma

Question 3

What is a functioning thyrotroph tumour called?

Answer 3

TSHoma

Question 4

What is a functioning gonadotroph tumour called?

Answer 4

Gonadotrophinoma

Question 5

What is a corticotroph tumour called?

Answer 5

Cushing’s Disease (corticotroph adenoma)

Question 6

How do you classify a pituitary tumour by size?

Answer 6

→ microadenoma = < 1 cm

→ macroadenoma = > 1 cm

Question 7

How do you classify a pituitary tumour radiologically?

Answer 7

→ sellar or suprasellar
→ compressing optic chiasm or not
→ invading cavernous sinus or not

Question 8

How do you classify a pituitary tumour by function?

Answer 8

→ excess secretion of hormone

→ no excess secretion of hormone = non-functioning adenoma

Question 9

How do you classify a pituitary tumour by benign or malignancy?

Answer 9

→ carcinoma very rare
→ mitotic index measured using Ki67 index (benign is <3%)
→ pituitary adenoma can have benign histology + malignant behaviour

Question 10

What the effect of hyperprolactinaemia on the gonadotrophin hormones?

Answer 10

→ Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
→ Inhibits kisspeptin release
→ decreases downstream homrone cascade e.g. less GRH, LH + FSH, testosterone + oestrogen

Question 11

What is the most common functioning pituitary adenoma?

Answer 11

prolactinoma

Question 12

What is the size of the prolactinoma usually proportional to?

Answer 12

serum prolactin

Question 13

How does the prolactinoma present?

Answer 13

→ Menstrual disturbance
→ Erectile dysfunction
→ Reduced libido
→ Galactorrhoea
→ Subfertility
→ Oligo-amenorrhoea
→ Osteoporosis

Question 14

What are the alternative physiological cause of elevated prolactin?

Answer 14

→ pregnancy / breastfeeding
→ stress (exercise, seizure, venepuncture)
→ nipple/chest wall stimulation

Question 15

What are the alternative pathological causes of elevated prolactin?

Answer 15

→ primary hypothyroidism
→ polycystic ovarian syndrome
→ chronic renal failure

Question 16

What are the alternative iatrogenic (drug-related) causes of elevated prolactin?

Answer 16

→ antipsychotics
→ SSRIs
→ anti-emetics
→ high dose oestrogen
→ opiates

Question 17

How do you confirm true elevation of serum prolactin?

Answer 17

→ no diurnal variation
→ not affected by food
→ consistent with clinical features

Question 18

What are the 2 possible explanations if a mild prolactin elevation has no consistency with clinical features + the medical history has been reviewed?

Answer 18

→ macroprolactin

→ stress

Question 19

What is macroprolactin?

Answer 19

→ “sticky prolactin”
→ a polymeric form of prolactin
an antigen–antibody complex of monomeric prolactin + IgG (normally <5% of circulating prolactin)
→ Recorded on assay as elevation of prolactin – needs alternative method to confirm (macroprolactin screening test)

Question 20

Why can stress cause a false positive elevation in serum prolactin?

Answer 20

→ stress of venepuncture (unsure why)

→ measure 20 minutes apart with indwelling cannula to minimise venepuncture stress

Question 21

What’s the next step after a true elevation of prolactin has been confirmed?

Answer 21

pituitary MRI

Question 22

How is prolactinoma treated?

Answer 22

→ first-line = medical
→ dopamine receptor agonists
e.g. CABERGOLINE
(bromocriptine doesn’t work as well) (also safe in preganancy)
→ aim to normalise serum prolactin + shrink prolactinoma

Question 23

How do dopamine receptor agonists work?

Answer 23

→ dopamine receptor agonists mimic the dopamine released from hypothalamic dopaminergic neurones
→ inhibits release of prolactin from lactotrophs

Question 24

What is the result of excess GH in children? Why?

Answer 24

gigantism

→ growth plates still active

Question 25

What is the result of excess GH in adults? Why?

Answer 25

acromegaly | → growth plates are closed

Question 26

What are the symptoms of acromegaly?

Answer 26

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

Question 27

How is acromegaly diagnosed? What test is done to confirm acromegaly?

Answer 27

→ measure GH after oral glucose load → serum GH levels should decrease in normal person → serum GH has paradoxical increase in acromegalic (prolactin often increases too) → should also have elevated serum IGF-1

Question 28

What is done after excess GH is confirmed?

Answer 28

pituitary MRI

Question 29

Why is it important to treat acromegaly?

Answer 29

→ increased risk of DM | → increased cardiovascular risk

Question 30

How is acromegaly treated?

Answer 30

→ first-line = surgical → trans-sphenoidal pituitary surgery → aim to normalise serum GH + IGF-1 → Can use medical treatment prior to surgery to shrink tumour or if surgical resection incomplete e.g. Somatostatin analogues eg octreotide – ‘endocrine cyanide’ or Dopamine agonists eg cabergoline (GH secreting pituitary tumours frequently express D2 receptors

Question 31

What is Cushing's syndrome vs. Cushing's disease?

Answer 31

→ both = too much cortisol or other glucocorticoid | → Cushing's disease is due to specifically a pituitary adenoma

Question 32

What are causes of Cushing's?

Answer 32

``` ACTH dependent → adrenal adenoma or carcinoma → taking steroids by mouth ACTH independent → pituitary dependent Cushing's disease → ectopic ACTH (lung cancer) ```

Question 33

What are the symptoms of Cushing's?

Answer 33

``` → mental changes → red cheeks → fat pads → striae → easy bruising → moon face → centripetal obesity → hypertension, etc... ```

Question 34

What clinical investigation results indicate Cushing’s Disease?

Answer 34

→ elevation of 24hr urine free cortisol (due to excess cortisol) → elevation of late night cortisol (loss of diurnal rhythm) → failure to suppress cortisol after oral dexamethasone (oral glucocorticoid) (should be supressed due to negative feedback)

Question 35

What's next after determining elevated cortisol levels?

Answer 35

measure ACTH to determine whether cause is ACTH dependent/independent

Question 36

What are non-functioning pituitary adenomas?

Answer 36

→ don't secrete any specific hormone → often present with visual disturbance (bitemporal hemianopia) → can present w hypopituitarism → serum prolactin could be raised if dopamine can travel down from hypothalamus

Question 37

How are non-functioning pituitary adenomas treated?

Answer 37

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