3.5 - Pituitary tumours Flashcards
What hormones do anterior pituitary cells release?
- somatotrophs - growth hormone (somatotrophin)
- lactotrophs - prolactin
- thyrotrophs - thyroid stimulating hormone (thyrotrophin)
- gonadotrophs - luteinising hormone, follicle stimulating hormone
- corticotrophs - adrenocorticotrophic hormone (corticotrophin)
What would a functioning tumour of somatotrophs cause?
Acromegaly
What would a functioning tumour of lactotrophs cause?
Prolactinoma
What would a functioning tumour of thyrotrophs cause?
TSHoma
What would a functioning tumour of gonadotrophs cause?
Gonadotrophinoma
What would a functioning tumour of corticotrophs cause?
Cushing’s disease (corticotroph adenoma)
What are the different ways to classify a pituitary tumour? (3)
- radiological (MRI)
- function
- benign or malignant
How is a pituitary tumour classified radiologically?
- size - microadenoma is <1cm, macroadenoma is >1cm
- sellar or suprasellar (grows out of sella turcica)
- compressing optic chiasm or not (suprasellar grows up)
- invading cavernous sinus or not (suprasellar grows sideways)
How is a pituitary tumour classified by function?
- functioning tumour - excess secretion of a specific pituitary hormone e.g. prolactinoma
- no excess secretion of pituitary hormone (non functioning adenoma)
How is a pituitary tumour classified as benign or malignant?
- pituitary carcinoma (cancer) 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
What does hyperprolactinaemia caused by a prolactinoma do to the HPG axis?
- PRL binds to PRL receptors on kisspeptin neurons in hypothalamus
- inhibits kisspeptin release
- decreases downstream GnRH –> LH/FSH –> T/Oes
- oligo-amenorrhoea / low libido / infertility / osteoporosis
What do prolactinomas do to serum prolactin?
- commonest functioning pituitary adenoma
- usually serum PRL > 5000 mU/L
- serum PRL proportional to tumour size
How do prolactinomas present? (5)
- menstrual disturbance
- erectile dysfunction
- reduced libido
- galactorrhoea (leaking of milk outside of lactation)
- subfertility
NB remember effects of prolactin on inhibiting HPG axis for symptoms!!
What are other types of causes of an elevated prolactin aside from a prolactinoma? (3)
- physiological
- pathological
- iatrogenic
What are examples of physiological causes of an elevated prolactin? (3)
- pregnancy/breastfeeding
- stress - exercise, seizure, venepuncture
- nipple/chest wall stimulation
What are examples of pathological causes of an elevated prolactin? (3)
- primary hypothyroidism
- PCOS
- chronic renal failure
What are examples of iatrogenic causes of an elevated prolactin? (5)
- antipsychotics
- selective serotonin reuptake inhibitors (SSRIs)
- anti-emetics
- high dose oestrogen
- opiates
What do you do once you have confirmed a true pathological elevation of serum prolactin?
Organise a pituitary MRI
How do we treat prolactinomas?
- first-line treatment is medical not surgical
- dopamine receptor agonists mainstay of treatment e.g. cabergoline (bromocriptine)
- safe in pregnancy
- aim to normalise serum PRL and shrink prolactinoma
- microprolactinomas need smaller doses than macroprolactinomas
How do dopamine receptor agonists work?
- the agonist mimics dopamine and binds to D2 receptors on anterior pituitary lactotrophs
- works like dopamine and prevents lactotrophs making PRL
What does a pituitary tumour secreting excess growth hormone cause in children and adults?
- children - gigantism
- adults - acromegaly
What is the mean diagnosis time for acromegaly?
10y - often insidious presentation
What are the symptoms of acromegaly? (8)
- sweatiness
- headache
- coarsening of facial features - macroglossia, prominent nose
- large jaw - prognathism
- increased hand and feet size
- snoring and obstructive sleep apnoea
- hypertension
- impaired glucose tolerance/diabetes mellitus
What are the mechanisms of growth hormone action?
- direct via growth hormone receptor from APG to tissues
- indirect via insulin-like growth factor (somatomedin) to tissues - APG –> liver –> tissues
How do we diagnose acromegaly?
- GH is pulsatile - so random measurement unhelpful
- 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 and PRL
What do we do once we confirm growth hormone excess?
Pituitary MRI to visualise pituitary tumour
What can untreated acromegaly cause?
Increased cardiovascular risk in untreated acromegaly
What is the treatment of 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 an acromegaly tumour prior to surgery?
Or after surgery to improve outcome?
- 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 two types of causes of Cushing’s syndrome?
- ACTH dependent
- ACTH independent
What are the ACTH dependent causes of Cushing’s syndrome? (2)
- Cushing’s disease (pituitary corticotroph adenoma)
- ectopic ACTH (e.g. lung cancer)
What are the ACTH independent causes of Cushing’s syndrome? (2)
- taking steroids by mouth (common)
- adrenal adenoma/carcinoma
What are some symptoms of Cushing’s syndrome? (12)
- red cheeks
- moon face
- fat pads (buffalo hump)
- thin skin
- easy bruising
- impaired glucose tolerance and high BP
- osteoporosis
- mental changes
- proximal myopathy
- purple striae
- pendulous abdomen
- poor wound healing
What is the difference between Cushing’s syndrome and Cushing’s disease?
- syndrome - excess cortisol
- disease - pituitary corticotroph adenoma secreting ACTH
What is the normal rhythm of cortisol release?
Diurnal - highest early morning, decreases throughout day (lowest at night) then increases to early morning
How do we investigate Cushing’s disease?
- 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 (should decrease as increased plasma cortisol reduces ACTH, suppressing cortisol levels)
Once we have confirmed hypercortisolism, how do we further investigate?
Measure ACTH and if high (ACTH dependent), do a pituitary MRI
What are non-functioning pituitary adenomas?
Do not secrete any specific hormones (but the tumour still causes symptoms)
What do non-functioning pituitary adenomas often present with?
Visual disturbance - bitemporal hemianopia
What hormonal issues can non-functioning pituitary adenomas cause?
- can present with hypopituitarism
- serum prolactin can be raised as dopamine cannot travel to pituitary stalk from hypothalamus
How do we treat large non-functioning pituitary adenomas?
Trans-sphenoidal surgery needed for larger tumours, particularly if visual disturbance
