Pituitary Tumors

Question 1

What are the 5 anterior pituitary cell types?

Answer 1

Somatotrophs
Lactotrophs
Thytotrophs
Gonadotrophs
Corticotrophs

Question 2

What does a tumour of somatotrophs cause?

Answer 2

Acromegaly

Too much GH

Question 3

What does a tumour of lactotrophs cause?

Answer 3

Prolactinoma

Too much prolactin

Question 4

What does a tumour of thyrotrophs cause?

Answer 4

TSHoma

Very rare

Question 5

What does a tumour of gonadotrophs cause?

Answer 5

Gonadotrophinoma

Very rare

Question 6

What does a tumour of corticotrophs cause?

Answer 6

Cushing’s disease
(Corticotroph adenoma)
Too much ACTH therefore too much cortisol

Question 7

What is the difference between Cushing’s syndrome and disease?

Answer 7

Disease = corticotroph adenoma

Question 8

How do we classify pituitary tumour radiologically?

Answer 8

Size
Sellar or Suprasellar
Compressing optic chiasm or not
Invading cavernous sinus or not

Question 9

What how do we classify pituitary tumour by size?

Answer 9

Microadenoma (<1cm)

Macroadenoma(>1cm)

Question 10

What is a functional pituitary tumour?

Answer 10

Excess secretion of a specific pituitary hormone

e.g. prolactinoma

Question 11

What is a non functional pituitary tumour?

Answer 11

No excess secretion of pituitary hormone

Non-functioning Adenoma

Question 12

Is pituitary cancer common?

Answer 12

Pituitary carcinoma very rare

Mitotic index measured using Ki67 index - benign is <3%

Question 13

Are pituitary tumours benign or malignant?

Answer 13

Pituitary adenomas can have benign histology but display malignant behaviour

Question 14

How does hyperprolactinaemia shut down the HGP axis?

Answer 14

Prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus

Inhibits kisspeptin release

Decreases in downstream GnRH

Decreased LH/FSH

Decreased Testosterone and Oestrogen

Causes oligo-amenorrhoea, low libido, infertility and osteoporosis

Question 15

What is the most common functional pituitary tumour?

Answer 15

Prolactinomas

Question 16

What is the serum prolactin proportional to?

Answer 16

Tumour size

>5000mU/L

Question 17

How does a prolactinoma present?

Answer 17

Menstrual disturbance
Erectile dysfunction
Reduced libido
Galactorrhea (milk production from the breast)
Sub-fertility

Question 18

What are the physiological causes of an elevated prolactin?

Answer 18

Pregnancy/breastfeeding
Stress: exercise, seizure, venepuncture
Nipple/chest wall stimulation

Question 19

What are the pathological causes of an elevated prolactin?

Answer 19

Primary hypothyroidism
Polycystic ovarian syndrome
Chronic renal failure, prolactin secreted by the kidneys and cannot be excreted

Question 20

What are the iatrogenic causes of an elevated prolactin?

Answer 20

Antipsychotics
Selective serotonin re-uptake inhibitors
Anti-emetics
(all work by dopaminergic pathway which inhibits prolactin)

High dose oestrogen
Opiates e.g. morphine

Question 21

Can prolactin levels vary in a day?

Answer 21

No diurnal variation

Not affected by food

Question 22

What do you consider if someone has a mild prolactin elevation, no clinical features and you have reviewed their medication list?

Answer 22

Macroprolactin

Stress of venipuncture

Question 23

What is macroprolactin?

Answer 23

‘sticky prolactin’
a polymeric form of prolactin
an antigen-antibody comped of monomeric prolactin and IgG (normally <5% of circulating prolactin

Recorded on assay as elevation
No impact on life
Can reassure patient

Question 24

How do you exclude the stress of venepuncture?

Answer 24

Cannulated prolactin series

Sequential serum [prolactin] measurement 20 mins apart with an indwelling cannula to minimise venipuncture stress

Question 25

When do you conduct a pituitary MRI?

Answer 25

Only once you have confirmed a true pathological elevation of serum prolactin

Question 26

What is the first line treatment of prolactinoma?

Answer 26

Medical not surgical Dopamine receptor agonists mainstay of treatments Cabergoline Safe in pregnancy Aims to normalise serum prolactin and shrink prolactinoma

Question 27

How do dopamine receptor agonists work?

Answer 27

Dopamine from hypothalamic dopaminergic binds to receptor and inhibits prolactin D2 agonists do the same

Question 28

What is the difficulty with acromegaly?

Answer 28

Often insidious presentation | Mean time to diagnosis from onset of symptoms = 10y

Question 29

What are the symptoms of acromegaly?

Answer 29

Sweatiness Headache ``` Coarsening of facial features - macroglossia - prominent nose Large jaw - prognathism Increased hands and feet Snoring and obstructive sleep apnea Hypertension Impaired glucose tolerance/ diabetes mellitus ```

Question 30

What is are the two mechanism of GH?

Answer 30

Via IGF-1 on the liver | Directly on muscle and bone

Question 31

How do we diagnose acromegaly?

Answer 31

GH pulsatile -so random measurement unhelpful Elevated serum IGF-1 Failed suppression (paradoxical rise) of GH following oral glucose load tolerance test Prolactin can be raised (co-secretion of GH and prolactin) Carpal tunnel syndrom

Question 32

What is done once GH is confirmed to be in excess?

Answer 32

Pituitary MRI to visualise pituitary tumour

Question 33

How doe we treat acromegaly?

Answer 33

First line treatment is surgery Trans-sphenoidal pituitary surgery Aim to normalise serum GH and IGF-1

Question 34

What can you do to treat acromegaly medically?

Answer 34

Medical treatment prior to surgery to shrink tumour or if resection is incomplete Somatostatin analogues Dopamine agonists Radiology (very slow)

Question 35

What are the symptoms of Cushing's?

Answer 35

``` Mental changes Red cheeks Moon face Easy brushing Lemon on a stick etc. ```

Question 36

What causes Cushing's?

Answer 36

Oral steroids Pituitary depende Cushing;s disease (pituitary adenoma) Ectopic ACTH (lung cancer) Adrenal adenoma or carcinoma

Question 37

How do you investigate Cushing's disease?

Answer 37

Elevated of 24h urine free cortisol - increased cortisol secretion Elevation of late nigh cortisol - salivary or blood test - loss of diurnal rhythm Failure to suppress cortisol after oral dexamethasone (exogenous glucocorticoid) - increased cortisol secretion

Question 38

What are non-functioning pituitary adenomas?

Answer 38

Don't secrete any specific hormone | Often present with visual disturbance (bitemporal hemianopia)

Question 39

How can someone with a non-functioning pituitary adenoma present?

Answer 39

Hypopituitarism Serum prolactin can be raised (dopamine cannot travel down pituitary stalk from hypothalamus)

Question 40

How can you treat non-functioning pituitary adenomas?

Answer 40

Trans-sphenoidal surgery needed for larger tumours, particular if visual disturbance 3rd line: Sellar radiotherapy