Pituitary Tumours

Question 1

What three characteristics are used to classify tumours?

Answer 1

Radiological
Function
Benign or malignant

Question 2

Outline how radiological findings (MRI) contribute to tumour classification

Answer 2

Size:
- Microadenoma <1cm (10mm)
- Macroadenoma >1cm (10mm)
Sellar or suprasellar
Compressing optic chiasm or not
Invading cavernous sinus or not

Question 3

Outline how function contributes to tumour classification

Answer 3

Excess secretion of a specific pituitary hormone, e.g. prolactinoma
No excess secretion of pituitary hormone (Non Functioning Adenoma)

Question 4

Describe benign or malignant tumour classification

Answer 4

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 5

Outline the effect of hyperprolactinaemia on the HPG axis

Answer 5

• Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus -> Inhibits kisspeptin release
• This decreases in downstream GnRH/LH/FSH/T/Oest
• Oligo-amenorrhoea/Low libido/Infertility/Osteoporosis

Question 6

Describe the effect of prolactin on GnRH pulsatility

Answer 6

Flattens it

Question 7

What is the commonest functioning pituitary adenoma?

Answer 7

Prolactinoma

Question 8

Describe serum prolactin levels in a person with a prolactinoma

Answer 8

Usually serum [prolactin] >5000 mU/L
Serum prolactin proportional to tumour size

Question 9

What are the symptoms of a prolactinoma?

Answer 9

Menstrual disturbance
Erectile dysfunction
Reduced libido
Galactorrhoea
Subfertility

Question 10

What are some physiological causes of an elevated prolactin?

Answer 10

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

Question 11

What are some other pathological causes of an elevated prolactin?

Answer 11

Primary hypothyroidism
Polycystic ovarian syndrome
Chronic renal failure

Question 12

What are some iatrogenic causes of an elevated prolactin?

Answer 12

Antipsychotics
Selective serotonin re-uptake inhibitors
Anti-emetics
High dose oestrogen
Opiates

Question 13

When should a pituitary MRI be organised during the investigation of a suspected prolactinoma?

Answer 13

Once you have confirmed a true pathological elevation of serum prolactin

Question 14

Is the first-line treatment of a prolactinoma surgical?

Answer 14

No it is medical

Question 15

How are prolactinomas treated and how does this differ depending on size?

Answer 15

Dopamine receptor agonists, e.g. Cabergoline (bromocriptine)
Aim is to normalise serum prolactin & shrink prolactinoma (act on D2 receptors)
Microprolactinomas will need smaller doses than macroprolactinomas

Question 16

Are dopamine receptor agonists safe to use in pregnancy?

Answer 16

Yes

Question 17

How would you describe the onset of acromegaly?

Answer 17

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

Question 18

What are the symptoms of acromegaly?

Answer 18

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

Question 19

What are the mechanisms of growth hormone action?

Answer 19

Growth hormone is released from the somatotrophs of the anterior pituitary and stimulates growth and development in body tissues.
GH also stimulates the liver to produce Insulin-like Growth Factor (somatomedin) - has GH-like effects.

Question 20

Why is a random GH measurement not useful in the diagnosis of acromegaly?

Answer 20

GH is pulsatile

Question 21

How is acromegaly diagnosed?

Answer 21

Elevated serum IGF-1
Failed suppression (‘paradoxical rise’) of GH following oral glucose load – oral glucose tolerance test
Prolactin can be raised – co-secretion of GH & prolactin
Once GH excess is confirmed, pituitary MRI is done to visualise pituitary tumour

Question 22

Why shouldn’t acromegaly be left untreated?

Answer 22

There is an increased cardiovascular risk

Question 23

How is acromegaly treated?

Answer 23

First-line treatment is surgical – trans-sphenoidal pituitary surgery
Aim to normalise serum GH and IGF-1
Radiotherapy - slow

Question 24

What medications can be used prior to surgery to shrink a tumour or if the surgical resection is incomplete in acromegaly?

Answer 24

Somatostatin analogues e.g., octreotide – ‘endocrine cyanide’ (can switch off other hormones, e.g. CCK)
Dopamine agonists e.g., cabergoline (GH secreting pituitary tumours frequently express D2 receptors)

Question 25

Why does Cushing’s syndrome occur?

Answer 25

Occurs due to an excess of cortisol or other glucocorticoid

Question 26

What causes Cushing’s syndrome?

Answer 26

ACTH independent:
- Taking steroids by mouth (common)
- Adrenal adenoma or carcinoma
ACTH dependent:
- Pituitary dependent Cushing’s disease (pituitary adenoma)
- Ectopic ACTH (lung cancer)

Question 27

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

Answer 27

Cushing’s syndrome - excess cortisol
Cushing’s disease is due to a corticotroph adenoma secreting ACTH

Question 28

What investigations are used for the diagnosis of Cushing’s Disease?

Answer 28

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

Question 29

Once hypercorticolism is confirmed in the investigation of Cushing’s Disease, what should you do?

Answer 29

Measure ACTH
If ACTH is high, do a pituitary MRI - ACTH dependent cause

Question 30

How are non-functioning pituitary tumours different from functioning tumours and what do they normally present with?

Answer 30

Don’t secrete any specific hormone
Often present with visual disturbance (bitemporal hemianopia)
Can also present with hypopituitarism
Serum prolactin can be raised (dopamine can’t travel down pituitary stalk from hypothalamus)

Question 31

How are non-functioning pituitary tumours treated?

Answer 31

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