(endo) pituitary tumours Flashcards
what is a tumour?
a large collection of cells growing uncontrollably
what are the most common types of tumours in the pituitary gland: benign or malignant?
benign - mostly not cancerous
why can benign pituitary tumours be harmful?
excessive hormone production
what are the five types of anterior pituitary cells?
somatotrophs, lactotrophs, gonadotrophs, thyrotrophs and corticotrophs
which hormones do the anterior pituitary cells produce?
somatotrophs - GH
lactotrophs - prolactin
thyrotrophs - TSH
corticotrophs - ACTH
gonadotrophs - LH/FSH
how does a pituitary tumour of the somatotrophs manifest?
acromegaly (adults)
gigantism (children)
what is a pituitary tumour of the lactotrophs called?
prolactinoma
what is a pituitary tumour of the thyrotrophs called?
TSHoma (extremely rare)
how does a pituitary tumour of the corticotrophs manifest?
Cushing’s disease
what is a pituitary tumour of the corticotrophs called?
corticotrophadenoma
what is a pituitary tumour of the gonadotrophs called?
gonadotrophinoma
how are pituitary tumours classified?
radiologically (MRI)
functionally
benign/malignant
how are pituitary tumour classified radologically?
based on
- size
- relation to sella turcica (sellar/suprasellar)
- compression of optic chiasm or not
- invasion of the caverous sinus or not
how are pituitary tumours visualised radiologically?
MRI scan
what are the two size classifications of pituitary tumours?
microadenomas (< 1cm/10mm)
macroadenomas (> 1cm/10mm)
which two nearby structures could pituitary tumours affect?
optic chiasm and caverous sinus
differentiate between sellar and suprasellar tumours
sellar = tumour that sits in the sella turcica
suprasellar = can grow out of the sella turcica
why are surgeons hesitant to enter the cavernous sinus?
due to the presence of multiple cranial nerves and the internal carotid artery (key for blood supply)
how are pituitary tumours classified based on function?
hypersecretion of a specific pituitary hormone (e.g. prolactinoma)
no excess secretion of pituitary hormone (non-functioning adenoma)
what is a non-functioning pituitary adenoma?
adenoma that does not result in excess secretion of pituitary hormone
how is the level of malignancy of pituitary tumours assessed?
using the Ki67 index to measure mitotic index (benign is <3%)
how does hyperprolactinaemia affect kisspeptin neurones?
excess prolactin bind to the kisspeptin neurones in the hypothalamus inhibiting kisspeptin release
downstream inhibition of GnRH/LH/FSH
reduced stimulation of testosterone and oestrogen production
can cause oligo-menorrhoea/amenorrhoea/low libido/infertility/osteoporosis
what is the function of kisspeptin neurones?
release kisspeptin to stimulate downstream release of GnRH then LH/FSH
what are the symptoms of hyperprolactinaemia?
low libido, oligomenorrhoea, amenorrhoea, infertility, osteoporosis
what is the most common functional pituitary adenoma?
prolactinoma
in what manner are GnRH and LH released?
in a pulsatile manner
what is serum prolactin for individuals with a prolactinoma?
> 5000mU/L
what is the relationship between prolactinoma size and serum prolactin levels?
serum prolactin levels are proportional to prolactinoma size
how do people with prolactinomas present?
menstrual distubances, erectile dysfunction, reduced libido, galactorrhoea, subfertility
what are physiological causes of elevated prolactin levels?
pregnancy/breastfeeding
stress: exercise, seizure, VENUPUNCTURE
nipple/chest wall stimulation
what are pathological causes of elevated prolactin levels?
primary hypothyroidism
polycystic ovaries syndrome (PCOS)
chronic renal failure
what are iatrogenic causes of elevated prolactin levels?
antipsychotics
selective serotonin reuptake inhibitors (SSRIs)
anti-emetics
high dose oestrogen
opiates
define iatrogenic
relating to an illness caused by a medical examination or treatment
why does primary hypothyroidism cause elevated prolactin?
in primary hypothyroidism, TRH is elevated which stimulates prolactin secretion
when a patient has elevated serum prolactin but no symptoms, what could be the cause?
macroprolactin, venupuncture
only possible reasons after medication list has been reviewed
what is macroprolactin?
a polymeric form of prolactin that forms an antigen-antibody complex with IgG antibodies in circulation = ‘sticky prolactin’
what is ‘sticky prolactin’?
macroprolactin, which binds to IgG antibodies in circulation
can macroprolactin be detected?
yes, is recorded on an assay as an elevation of prolactin
how can macroprolactin and normal prolactin be differentiated?
using a special test
what does elevated prolactin have to do with venepuncture?
the first blood sample may have a high prolactin due to venepuncture stress (the stress of having a blood test)
how can venepuncture stress be excluded so it affects serum prolactin levels less?
use a cannulated prolactin series
sequential serum prolactin measurements 20 minutes apart with an indwelling cannula
what is a cannulated prolactin series?
sequential serum prolactin measurement 20 minutes apart with an indwelling cannula to minimise venepuncture stress
what will be shown on a cannulated prolactin series for an individual with hyperprolactinemia?
serum prolactin levels will remain high with every measurement
what will be shown on a cannulated prolactin series for an normal person?
prolactin will initially be elevated but serum prolactin levels will reduce gradually with each measurement
what is the next step after a true pathological elevation of serum prolactin has been confirmed?
organise a pituitary MRI
how are prolactinomas treated?
dopamine receptor agonist (e.g. cabergoline, bromocriptine)
what is the preferred first-line treatment for prolactinomas?
medical, not surgical
only type of APG tumours preferentially treated w medicine not surgery
how do dopamine receptor agonists reduce prolactin and shrink prolactinomas?
lactotrophs are covered in dopamine D2 receptors
when a dopamine receptor agonist (e.g. cabergoline) binds to the receptor, it has the same effect as dopamine binding
dopamine inhibits prolactin release from the APG lactotrophs
give an example of a dopamine receptor agonist
cabergoline/bromocriptine
can cabergoline be used in by pregnant women?
yes, safe to use in pregnancy
how are microprolactinomas treated in comparison to macroprolactinomas?
with a smaller dose of the chose dopamine receptor agonist (e.g. smaller dose of cabergoline)
how long does it take to diagnose acromegaly from the onset of symptoms?
on average 10 years due to insidious presentation
what are the symptoms of acromegaly?
sweatiness
headaches
coarsening of facial features (macroglossia, prominent nose/jaw)
prognathism (prominent jaw)
increased hand and feet size
snoring & obstructive sleep apnoea
hypertension
impaired glucose tolerance/diabetes mellitus
what is macroglossia?
abnormal enlargement of the tongue
what is prognathism?
prominent jaw
which clinical feature is consistent with a raised prolactin level: hirsutism, menorrhagia, amenorrhea or increased libido?
amenorrhoea (prolactin inhibiting kisspeptin neurones, suppression of GnRH and therefore LH and FSH release)
what is menorrhagia?
heavy periods
why can adults not be diagnosed with gigantism but children can?
in adults, the epiphyseal growth plates are fused as so the excess GH cannot act on osteocytes to cause hyperproliferation and subsequent increased bone length which is possible in children as they have unfused epiphyseal growth plates
what causes obstructive sleep apnoea in patients with acromegaly?
increased soft tissue growth in the larynx causes obstruction
why is it important not to leave acromegaly untreated?
can also drive hypertension, impaired glucose tolerance and increase cardiovascular risk
how can acromegaly lead to diabetes mellitus?
increased GH can cause insulin resistance that can lead to diabetes mellitus
why are the pituitary tumours that cause acromegaly usually very big?
as disease takes 10 years on average to be identified and diagnosed = plenty of time for tumour growth
how does GH affect growth directly and indirectly?
direct - binds to GH receptors on bone, muscle and soft tissue causing growth and development
indirect - stimulates IGF-1 release from liver
what is IGF?
insulin-like growth factor (somatomedin)
what is IGF alternatively known as?
somatomedin
what is the manner in which GH is secreted?
in a pulsatile manner
how is acromegaly diagnosed?
test for elevated serum IGF-1
failed suppression of GH levels following a glucose load in an oral glucose tolerance test
differentiate between the response of an acromegalic and a normal patient to an oral glucose tolerance test
normal patient - GH levels fall after glucose load
acromegalic patient - GH levels paradoxically and abnormally increase after glucose load
what other APG hormone can be elevated in acromegalic patients?
prolactin (can be co-secreted w GH)
once excess GH is confirmed, what is the next step in the management of acromegalic patients?
pituitary MRI to visualise tumour
what is the first-line treatment of acromegaly?
transphenoidal pituitary surgery to surgically resect the pituitary tumour
why is serum GH not tested to diagnose acromegaly?
as GH secretion is pulsatile so random measurement unhelpful
why can drugs be used prior to/after pituitary surgery for acromegaly?
before - to shrink the tumour (reduce tumour size)
after - remove remaining tumour if surgical resection is incomplete
which two drugs are commonly prescribed to treat acromegaly?
somatostatin analogues (octreotide)
dopamine agonist (cabergoline)
what is the mechanism of action of octreotide in acromegaly?
somatostatin analogue that inhibits GH secretion
what is the mechanism of action of cabergoline in acromegaly?
dopamine agonist that inhibits prolactin secretion from some GH secreting tumours that can co-secrete prolactin
why is a dopamine agonist prescribed for acromegaly?
dopamine agonists are usually prescribed for prolactinomas BUT some GH secreting pituitary tumours co-secrete prolactin AND also have D2 receptors that can be targeted
what is a common side effect of using octreotide?
can inhibit gut hormones causing diarrhoea
what are the main treatments for acromegaly?
transphenoidal pituitary surgery
somatostatin analogue/dopamine agonist
radiotherapy (slow)
why is radiotherapy not usually used to treat acromegaly?
too slow
what are the symptoms of Cushing’s syndrome?
red cheeks moon face purple striae easy bruising, thin skin centripetal obesity (pendulous abdomen) buffalo hump (fat pad) osteoporosis mental changes (depression) osteoporosis proximal myopathy (muscle weakness)
why does Cushing’s syndrome occur?
occurs due to an excess of cortisol (or other glucocorticoid)
what are the four causes of Cushing’s syndrome?
ACTH independent = excess steroid intake by mouth (common), adrenal adenoma/carcinoma
ACTH dependent = Cushing’s disease (corticotroph adenoma), ectopic ACTH production (lung cancer)
what are the ACTH dependent causes of Cushing’s syndrome?
corticotroph adenoma
ectopic ACTH production (lung cancer)
what are the ACTH independent causes of Cushing’s syndrome?
adrenal adenoma/carcinoma
excess steroid intake by mouth
differentiate between ACTH dependent and ACTH independent causes of Cushing’s syndrome
ACTH dependent means the excess cortisol is caused by excess ACTH
ACTH independent means the cortisol increase is caused by excess cortisol directly (i.e. has nothing to do w ACTH)
differentiate between Cushing’s syndrome and Cushing’s disease
Cushing’s syndrome = disease of excess cortisol
Cushing’s disease = disease of excess cortisol caused specifically by ACTH-secreting corticotroph adenoma
what is the most common cause of Cushing’s syndrome?
taking excess steroid by mouth
which three investigations are done to investigate Cushing’s disease?
elevation of cortisol levels in a 24 hour urine test
elevation of late night cortisol on a blood or salivary test (loss of diurnal rhythm)
failure to suppress cortisol after oral dexamethasone (exogenous glucocorticoid)
why is oral dexamethosone given to investigate Cushing’s disease?
oral dexamethosone is an exogenous glucocorticoid which, by negative feedback, should suppress ACTH secretion and therefore cortisol secretion however in Cushing’s cortisol levels remain high
why is a blood/salivary test done to investigate Cushing’s disease?
to investigate whether there is a late night elevation of cortisol (i.e. has the diurnal rhythm of cortisol secretion been lost?)
what should be done once hypercortisolism has been confirmed on a blood test?
measure ACTH and if that is high, schedule a pituitary MRI
what are non-functioning pituitary adenomas?
adenomas of the pituitary gland that do not hypersecrete a specific hormone
how do non-functioning pituitary adenomas usually present?
visual disturbance (bitemporal hemianopia) - just grow and compress optic chiasm
maybe hypopituitarism and raised prolactin
why can serum prolactin be raised in non-functioning pituitary adenomas?
adenoma can grow so large that the pituitary stalk is compressed preventing hypothalamic dopamine from inhibiting prolactin secretion from lactotrophs
how are non-functioning pituitary adenomas treated?
trans-sphenoidal pituitary surgery to resect tumour
