1B pituitary tumours Flashcards
What would a tumour of somatotrophs cause?
Acromegaly
What would a tumour of lactotrophs cause?
Prolactinoma
What would a tumour of thyrotrophs cause?
TSHoma
What would a tumour of gonadotrophs cause?
Gonadotrophinoma
What would a tumour of corticotrophs cause?
Cushing’s disease (corticotroph adenoma)
What are the different ways to classify a pituitary tumour?
- Radiological (MRI)
- Function
- Benign or malignant
What are the subclassifications of radiological (MRI) scans for pituitary tumours?
- Size- microadenoma is <1cm and macroadenoma is >1cm
- Sellar or suprasellar (grows out of sella turcica)
- Compressing optic chiasm or not
- Invading cavernous sinus or not
What are the function subclassifications?
- Excess secretion of a specific pituitary hormone e.g. prolactinoma
- No excess secretion of pituitary hormone (non functioning adenoma)
How are pituitary tumours classified as benign or malignant?
- Pituitary carcinoma- very rare (<0.5% of pituitary tumours)
- Mitotic index measured using Ki67 index- <3% means tumour is benign
- Pituitary adenomas can have benign histology but display malignant behaviour
What would hyperprolactinaemia caused by a prolactinoma do to HPG axis?
- PRL binds to PRL receptors on kisspeptin neurons in hypothalamus
- Inhibits kisspeptin release
- Decreases in downstream GnRH → LH/FSH → T/Oest
- Oligo-amenorrhoea/low libido/infertility/osteoporosis
What do prolactinomas do to serum PRL?
- Commonest functioning pituitary adenoma
- Usually serum PRL >5000 mU/L
- Normal levels: 530mU/L
- Serum PRL proportional to tumour size
How does hyperprolactinaemia caused by a prolactinoma present?
- Menstrual disturbance
- Erectile dysfunction
- Reduced libido
- Subfertility
- Galactorrhoea (milk production outside of breastfeeding- men can also get galactorrhoea but unusual)
What are other causes of elevated PRL aside from a prolactinoma?
-
Physiological
- Pregnancy/breastfeeding
- Stress: exercise, seizure, venepuncture
- Nipple/chest wall stimulation
-
Pathological
- Primary hypothyroidism
- PCOS
- Chronic renal failure
-
Iatrogenic
- Antipsychotics
- Anti-emetics
- Opiates
- Selective serotonin reuptake inhibitors (SSRIs)
- High dose oestrogen
What is a true elevation in serum PRL and why is it important to get?
- No diurnal variation, not affected by food
- Confirm true elevation in serum PRL as there are many false positives
What could it be when you see a mild elevation in serum PRL but no clinical features of prolactinoma and you’ve checked the medication list?
- Macroprolactin
- Venepuncture
What is macroprolactin?
- Majority of circulating PRL is monomeric and biologically active
- Macroprolactin is a ‘sticky’ polymeric form of PRL that is an antigen-antibody complex of monomeric PRL and IgG (normally <5% of circulating PRL)
- Recorded on assay as elevation of PRL- needs alternative method to confirm
- Limited bioavailability and bioactivity
- Can reassure patient
How do we deal with stress of venepuncture?
By a cannulated PRL series:
Sequential serum PRL measurement 20 mins apart with an indwelling cannula to minimise venepuncture stress
What do you do if you’ve confirmed a true pathological elevation of serum PRL?
Organise a pituitary MRI
How do we treat prolactinomas?
- First-line treatment is medical not surgical
- Dopamine receptor agonists are mainstay of treatment like cabergoline (bromocriptine)
- Safe in pregnancy
- Aim is to normalise serum PRL and shrink prolactinoma
- Microprolactinomas need smaller doses than macroprolactinomas
How do dopamine receptor agonists work?
1) The agonist mimics dopamine and it binds to D2 receptors on anterior pituitary lactotrophs
2) Works like dopamine and prevents lactotrophs making PRL
What are the symptoms of acromegaly?
- Sweatiness
- Headache
- Coarsening of facial features- macroglossia, prominent nose
- Large jaw- prognathism
- Increase hand and feet size
- Snoring and obstructive sleep apnoea
- Hypertension
- Impaired glucose tolerance/diabetes mellitus
How do we diagnose acromegaly?
- GH is pulsatile- so random measurement is unhelpful
- Elevated serum IGF-1 helps
- Failed suppression (paradoxical rise) of GH following oral glucose load- oral glucose tolerance test- we don’t know why
- PRL can be raised- co-secretion of GH and PRL
What do we do once we confirm GH excess for acromegaly?
Pituitary MRI to visualise pituitary tumour
Why do we need to treat acromegaly?
Increased cardiovascular risk in untreated acromegaly
What is the treatment for acromegaly?
- First line treatment is surgical- trans-sphenoidal pituitary surgery
- Aim to normalise serum GH and IGF-1
- Could use radiotherapy (slow)
What can we use to shrink tumour prior to surgery for acromegaly?
- Somatostatin analogues e.g. octreotide- ‘endocrine cyanide’
- Dopamine agonists e.g. cabergoline (GH secreting pituitary tumours frequently express D2 receptors)
What is Cushing’s syndrome?
Occurs due to an excess of cortisol or other glucocorticoid
What are the causes of Cushing’s syndrome?
ACTH independent
- Taking steroids by mouth (common)
- Adrenal adenoma or carcinoma
ACTH dependent
- Cushing’s disease (corticotroph adenoma)
- Ectopic ACTH (lung cancer)
Difference between Cushing’s disease and syndrome?
- Syndrome: excess cortisol
- Disease: corticotroph adenoma secreting ACTH
What investigations are performed for Cushing’s?
- 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
Once hypercortisolism is confirmed, what further investigations are made?
Measure ACTH and if it’s high, do a pituitary MRI scan to find tumour
What do non-functioning pituitary adenomas often present with?
Bitemporal hemianopia
What problems can non-functioning pituitary adenomas cause?
- Can present with hypopituitarism
- Serum PRL can be raised (dopamine can’t travel down pituitary stalk from hypothalamus)- this is because tumour compresses/pinches posterior pituitary stalk
How do we treat larger pituitary tumours?
Trans-sphenoidal surgery needed for larger tumours, particularly if visual disturbance
