Pituitary Tumours

Question 1

What are the 5 types of cells of the anterior pituitary and what hormones do they produce?

Answer 1

Somatotrophs - GH
Lactotrophs - Prolactin
Thyrotrophs - TSH
Gonadotrophs - LH / FSH
Corticotrophs - ACTH

Question 2

What are the 5 different conditions associated with hyperplasia of the 5 different types of cells?

Which of these 5 conditions is most common?

Answer 2

Somatotrophs - gigantism in children or acromegaly in adults
Lactotrophs - prolactinoma
Thyrotrophs - TSHoma (rare)
Gonadotrophs - Gonadotrophinoma
Corticotrophs - Cushing’s disease (corticotroph adenoma)

Most common = prolactinoma

Question 3

Cushing’s syndrome Vs Cushing’s disease?

Answer 3

Cushing’s syndrome - refers to excess cortisol levels (or other corticosteroid levels) that can come from internal or external sources

Cushing’s disease - when a pituitary tumour causes the body to make too much cortisol (makes up majority of Cushing’s syndrome cases)

Question 4

Where does the pituitary gland sit? How big is it normally?

How big is a growth in the pituitary gland seen on a radiological MRI?

What happens to the structures around a pituitary tumour?

Answer 4

Sits on the sella turcica - about 1cm

Microadenoma = <1cm
Macroadenoma= >1cm

Suprasellar (extending above the sella turcica)
Compresses the optic chiasm
Cavernous sinuses lie on either side of the optic chiasm, which contain the internal carotid and some CNs - these can be damaged due to the tumour itself invading the cavernous sinus, or during pituitary surgery

Question 5

What happens to the function of a pituitary gland when there is a pituitary tumour?

Answer 5

Excess secretion of a specific pituitary hormone or no excess secretion of a pituitary hormone (non-functioning adenoma)

Question 6

Are pituitary tumours benign or malignant?

Answer 6

Mostly benign (not cancers)
Pituitary carcinomas (cancers) are v. rare

Question 7

Why can tumours be mis-classified?

Answer 7

Pituitary adenomas can have benign histology but display malignant behaviour i.e. agressive cell turnover under a microscope, affecting many structures around as they are located in a small area etc.

Question 8

What happens when there is hyperprolactinaemia to the rest of the hypothalamic-pituitary-gonadal axis?

Answer 8

Excess prolactin binds to kisspeptin neurons in the hypothalamus
Kisspeptin hormone release is inhibited
This affects the pulsatility of gonadotrophs
Decrease in GnRH / LH / FSH/ Testosterone / Oestrogen
Leads to oligo or amenorrhoea / low libido / infertility / osteoporosis

Question 9

How much prolactin is produced in a prolactinoma (functioning tumour)?

How does the size of the pituitary tumour relate to the prolactin produced?

Answer 9

Usually serum prolactin >5000 mU/L

The bigger the tumour, the higher the prolactin release

Question 10

How do prolactinomas present clinically?

Answer 10

Menstrual disturbance - oligomenorrhoea / amenorrhoea
Erectile dysfunction
Reduced libido
Galactorrhoea (milk production outside of breastfeeding)
Subfertility - prevents sperm production in men, egg release in women

Question 11

What are some other causes of elevated prolactin levels other than pituitary tumours?

(HINT: think of physiological, pathological, and iatrogenic reasons)

Answer 11

Physiological: pregnancy / breastfeeding; stress - exercise, seizure, venepuncture (from blood test); nipple / chest wall stimulation

Pathological: primary hypothyroidism (lack of T3/T4, TSH increases, TRH increases, and TRH also stimulates prolactin release); PCOS; chronic renal failure

Iatrogenic (drugs): anti-psychotics; SSRIs, anti-emetics; high dose oestrogen; opiates

Question 12

When is it best to measure prolactin?

What may affect a ‘true’ elevation in serum prolactin and why? False positives are common.
e.g. someone with slightly elevated prolactin but showing no symptoms

Answer 12

No diurnal variation or affected by food, can be measured any time

1. Macroprolactin - sticky prolactin that binds together resulting in a high reading
2. Stress of venepuncture (blood test) - can be avoided by taking a cannulated prolactin series where a drip is placed in the vein of the arm, patient settles for 20 mins, samples taken 30 mins apart
   (overtime the anxiety comes down, so the prolactin comes down to normal)

Question 13

When should a pituitary MRI be ordered?

Answer 13

Once a true pathological prolactin elevation is confirmed

Question 14

What is the treatment for a prolactinoma?

Answer 14

Dopamine receptor agonists (e.g. Cabergoline) - bind to dopamine receptors and stop prolactin release
Safe during pregnancy
Dosage depends on size of tumour

Question 15

How do dopamine receptor agonists work?

Use your knowledge on how dopamine affects prolactin release from lactotrophs.

Answer 15

Dopamine inhibits prolactin release
Lactotrophs have D2 receptors, dopamine binds onto the D2 receptors that then prevents prolactin release
A dopamine receptor agonist does the same job - lactotrophs eventually shrink

Question 16

How does acromegaly present?

Answer 16

Insidiously due to gradual progression in appearance - e.g. over 10yrs

Coarsening of facial features - difficult to spot due to gradual change
Sweatiness
Headaches
Large hands and feet
Large jaw - prognathism 
Snoring / sleep apnea 
Hypertension
Impaired glucose tolerance / DM (GH anatgonises actions of insulin)

Symptoms mainly due to enlarging of soft tissue

Question 17

What is the mechanism of GH?

Answer 17

GH - travels to liver to stimulate IGF-1 production

GH and IGF-1 act on bone and body tissues to promote growth

Question 18

How is acromegaly diagnosed?

Why are serum GH levels not enough?

Answer 18

GH is pulsatile, so random measurements are not insightful
Check for elevated serum IGF-1
Give a patient an oral glucose load - in normal patients, GH goes down, however, in acromegaly, GH goes up
This is known as a paradoxical rise
Then look at MRI scans

Question 19

How is acromegaly treated?

Answer 19

Due to effects on BGL, usually patients are given trans-sphenoidal pituitary surgery (surgery up the nose, drill through the sphenoid sinus and sella turcica to reach pituitary) 
Somatostatin analogues (e.g. octreotide) - stop growth analogues can stop GH secretion to help make the tumour smaller
Tumours may also express D2 receptors -  treated with dopamine receptor agonists

Question 20

What is Cushing’s Syndrome?

How does it present clinically?

Answer 20

Too much cortisol production - weak muscles, central weight gain, stretch marks, thin skin, easy bruising. impaired glucose tolerance, hypertension, red cheeks, poor wound healing, depression, osteoporosis etc.

Question 21

What is cushing’s disease?

Answer 21

Excess cortisol production due to corticotroph adenoma secreting excess ACTH

Question 22

Cushing’s syndrome can be ACTH dependent or ACTH independent?

What is meant by that?

Answer 22

ACTH dependent - increase in cortisol production due to increase in ACTH production e.g. in cushing’s disease or ectopic ACTH (lung cancer)
ACTH independent - increase in cortisol production not related to ACTH production e.g. taking steroids by mouth (common) or adrenal adenoma / carcinoma

Question 23

How can Cushing’s be investigated?

Answer 23

Measure all the cortisol released into the urine over 24hrs (to level out diurnal rhythm)
In cushing’s disease, dirunal rhythm of cortisol is lost
So even late-night cortisol in saliva or blood will be high

Oral dexamethasone given to patient - normally suppresses cortisol but does not affect patients with cushing’s disease

Question 24

Once hypercortisolism is confirmed, what can be measured to see if the cortisol elevation is ACTH dependent or independent?

Answer 24

Measure ACTH levels - high ACTH suggests ACTH dependent

Order pituitary MRI scan to confirm cushing’s disease

Question 25

What is a non-functioning pituitary adenoma?

How do they present clinically?

Answer 25

Do not secrete any specific hormone

Often present as visual disturbance e.g. bitemporal hemianopia, or hypopituitarism, or elevated prolactin levels (as dopamine may not be able to travel down the stalk from the hypothalamus to inhibit prolactin)

Question 26

How are non- functioning pituitary adenomas treated?

Answer 26

Trans-sphenoidal surgery needed for larger tumours, particularly if visual disturbance

Question 27

30F discontinued the oral contraceptive pill 9 months ago to plan for a pregnancy.
She has not had a period since.

What investigation would you do next?

Answer 27

Give her a pregnancy test
Ask about any other medications she is taking
Check her weight / BMI

Question 28

30F -
Pregnancy test negative
BMI 20 kg/m2
No medications

What would you do next?

Answer 28

Do a blood test to check anterior pituitary hormones and thyroid function

Question 29

30F- 
Oestradiol 	<70 pmol/L (>200) 
FSH	          	0.7 mU/L (1.5 – 10)
LH  	          	0.8 mU/L (2 - 10)
Prolactin      	15000 IU/L (<500)
Macroprolactin negative
Normal thyroid function

What does this show and what would you do next?

Answer 29

Low oestradiol, FSH anf LH
Very elevated prolactin that is not due to macro-prolactin
Normal thyroid function

Order a pituitary MRI

Question 30

30F -
Pituitary MRI shows a small (0.5cm) pituitary tumour – a presumed microprolactinoma

What would you do next?

Answer 30

Offer her treatment: replace hormones - e.g. oestrogen plus progesterone monthly, also FSH and LH as she is trying to get pregnant
Dopamine receptor agonists (e.g. Cabergoline) - safe during pregnancy