1b// Pituitary Tomours Flashcards
What are the anterior pituitary cells and their hormones?
Somatotrophs= Growth Hormone (somatotrophin)
Lactotrophs= Prolactin
Thyrotrophs= Thyroid stimulating hormone (TSH) (thyrotrophin)
Gonadotrophs= luteinising hormone and follicle stimulating hormone (LH and FSH)
Corticotrophs= Adrenocorticotrophic hormone (ACTH, corticotrophin)
What happens with functioning tumours of the anterior pituitary?
somatotrophs= acromegaly
lactotrophs= prolactinoma
thyrotrophs= TSHoma
gonadotrophs= gonadotrophinoma
corticotrophs= cushing’s disease (corticotroph adenoma)
What categories can you categorise pituitary tumours in?
Radiological (MRI)…
* Size - Microadenoma <1cm - Macroadenoma >1cm * Sellar or suprasellar * Compressing optic chiasm or not * Invading cavernous sinus or not
Function…
* Excess secretion of a specific pituitary hormone - E.g., prolactinoma * No excess secretion of pituitary hormone (non-functioning adenoma)
Benign or malignant…
* 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
What does hyperprolactinaemia cause?
inhibits kisspeptin neurones
How are kisspeptin neurones inhibited and what does it cause?
1) prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus
2) inhibits kisspeptin release
3) decreases in downstream GnRH/ LH/ FSH/ T/ Oest
4) oligo-amenorrhoea/ low libido/ infertility/ osteoporosis
What is the commonest functioning pituitary adenoma?
prolactinomas
what is the serum concentration of prolactin proportional to with a prolactinoma?
tumour size
What are the symptoms of prolactinomas?
menstrual disturbance
erectile dysfunction
reduced libido
galactorrhoea
subfertility
What are other physiological causes of an elevated prolactin?
pregnancy/ breastfeeding
stress: exercise, seizure, venepuncture
nipple/ chest wall stimulation
What are other pathological causes of an elevated prolactin?
primary hypothyroidism
polycystic ovarian syndrome
chronic renal failure
What are other latrogenic causes of an elevated prolactin?
antipsychotics
selective serotonin re-uptake inhibitors
anti-emetics
high dose oestrogen
opiates
What should you do once you’ve confirmed the true pathological elevation of serum prolactin?
pituitary MRI
How do you treat prolactinomas?
- First-line treatment is medical not surgical
- Dopamine receptor agonists mainstay of
treatment - Cabergoline (bromocriptine)
- Safe in pregnancy
- Aim is to normalise serum prolactin & shrink prolactinoma
- Microprolactinomas will need smaller doses than macroprolactinomas
How do dopamine receptor agonists work?
1) normally, anterior pituitary lactotrophs secrete prolactin
- they have D2 receptors (for dopamine)
- dopamine from hypothalamic dopaminergic neurones binds to D2 receptors and stops prolactin secretion
2) D2 (dopamine) receptor agonists bind to the D2 receptors and stop prolactin secretion
What does excess GH cause?
acromegaly in adults
gigantism in children
What are symptoms of acromegaly? (10)
- Sweatiness
- Headache
- Coarsening of facial features
- Macroglossia
- Prominent nose
- Large jaw - prognathism
- Increased hand and feet size
- Snoring & obstructive sleep apnoea
- Hypertension
- Impaired glucose tolerance/diabetes mellitus
What is the average time of diagnosis from start of symptoms for acromegaly and why?
Often insidious presentation – mean time to diagnosis from onset of symptoms = 10y
What is the mechanism for GH?
How can you diagnose acromegaly?
Gh is pulsatile- so random measurements are unhelpful
Elevated of serum IGF-1
Failed suppression (paradoxical rise) of GH following oral glucose load- oral glucose tolerance test
Once confirm GH excess, pituitary MRI to visualise pituitary tumour
What is the first line treatment for acromegaly?
surgical- trans-sphenoidal pituitary surgery
What risk is increased with untreated acromegaly?
increased cardiovascular risk
What is the aim for treatment for acromegaly?
normalise GH and IGF-1
What is the purpose of medical treatment for acromegaly?
Can use medical treatment prior to surgery to shrink tumour or if surgical resection incomplete
Somatostatin analogues eg octreotide –
‘endocrine cyanide’
Dopamine agonists eg cabergoline (GH secreting pituitary tumours frequently express D2 receptors)
What is a treatment for acromegaly but is slow?
radiotherapy
What is cushing’s syndrome?
excess cortisol
What causes cushing’s syndrome?
due to a pituitary corticotroph adenoma secreting ACTH
What are symptoms of cushing’s syndrome?
mental changes (depression)
osteoporosis
impaired glucose tolerance (diabetes)
high blood pressure
proximal myopathy (muscle weakness) (thin arms and legs)
easy bruising
moon face
red cheeks
fat pads
thin skin
purple striae
pendulous abdomen
poor wound healing
How do you investigate cushing’s syndrome?
What is cushing’s disease dependent on?
ACTH
Give 2 examples of ACTH dependent and independent reasons for hypercortisolism?
ACTH dependent…
- Cushing’s disease (pituitary corticotroph adenoma)
- ectopic ACTH (e.g., lung cancer)
ACTH independent…
- taking steroids by mouth
- adrenal adenoma or carcinoma
What should you do once confirmed hypercortisolism?
measure ACTH, if ACTH Is high do a pituitary tumour
What can non-functioning pituitary adenomas do to vision?
they don’t secrete any hormone
bitemporal hemianopia
What can non-functioning pituitary adenomas present with to do with hormones?
hypopituitarism
serum prolactin can be raised (dopamine can’t travel down pituitary stalk from hypothalamus)
How do you treat non-functioning pituitary tumours that cause disturbances?
trans-sphenoidal surgery needed for larger tumours, particularly is visual disturbance
