3.5 - Pituitary tumours Flashcards by Savita Ramkumar

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)

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What would a functioning tumour of somatotrophs cause?

Acromegaly

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What would a functioning tumour of lactotrophs cause?

Prolactinoma

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What would a functioning tumour of thyrotrophs cause?

TSHoma

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What would a functioning tumour of gonadotrophs cause?

Gonadotrophinoma

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What would a functioning tumour of corticotrophs cause?

Cushing’s disease (corticotroph adenoma)

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What are the different ways to classify a pituitary tumour? (3)

radiological (MRI)
function
benign or malignant

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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)

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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)

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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

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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

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What do prolactinomas do to serum prolactin?

commonest functioning pituitary adenoma
usually serum PRL > 5000 mU/L
serum PRL proportional to tumour size

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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!!

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What are other types of causes of an elevated prolactin aside from a prolactinoma? (3)

physiological
pathological
iatrogenic

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What are examples of physiological causes of an elevated prolactin? (3)

pregnancy/breastfeeding
stress - exercise, seizure, venepuncture
nipple/chest wall stimulation

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What are examples of pathological causes of an elevated prolactin? (3)

primary hypothyroidism
PCOS
chronic renal failure

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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? ## Footnote 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