3.5 Pituitary Tumours Flashcards
A tumour is a proliferation of a cell type, what would be caused by a tumour arising from somatotrophs.
Acromegaly - too much GH
What is a tumour made up from lactotrophs called?
prolactinoma
What is a tumour made up from thyrotrophs called?
TSHoma
What is a tumour made up from gonadotrophs called?
Gonadotrophinoma
What is a tumour made up from corticotrophes called?
cotricotroph adenoma
What is an adenoma?
Benign tumour of the pituitary gland
What disease does a corticotroph adenoma cause?
Cushing’s disease
How do we measure the size of a pituitary tumour?
MRI
What are the 4 ways we can radiologically classify a pituitary tumour?
size
sellar or suprasellar
compressing optic chiasm or not
invading cavernous sinus or not
What are the two size classifications of a pituitary tumour and the parameters?
microadenoma <1cm
macroadenoma >1cm
How do we classify pituitary tumours according to function?
Functioning: causes excess secretion of a specific pituitary hormone (e.g. prolactinoma - will go by this name)
Non-functioning: no excess secretion
Why can pituitary adenomas have benign histology but display malignant behaviour?
lack of space, lots of other structures easily affected.
*benign according to classification but can cause many symptoms as affecting other structures so seems malignant
Are pituitary tumours typically benign or malignant?
benign
pituitary carcinoma very rare <0/5%
What are the three factors to consider when classifying pituitary tumours?
Radiological
Function
Benign/malignant
How does (too much) prolactin inhibit GnRH?
- prolactin binds to prolactin receptors on kisspeptin neurones in hypothalamus
- inhibits kisspeptin release
- decreases in downstream GnRH (and therefore LH/FSH)
What is the pattern of GnRH release?
pulsatile
What are the symptoms will you see if excess PRL inhibits GnRH?
- low libido
- erectile dysfunction
- loss of periods
- reduced pubic hair
- infertility
- osteoporosis
What does excess PRL inhibiting GnRH an example of?
secondary hypogonadism
What is the commonest functioning pituitary adenoma?
prolactinoma
What is serum prolactin in a patient with prolactinoma
> 5000mU/L
usually men ~300, women <600
In a patient with prolactinoma, what does the level of serum prolactin indicate?
serum prolactin proportional to tumour size
How does prolactinoma usually present? (5)
menstrual disturbance erectile dysfunction reduced libido galactorrhoea (usually in women) - production of milk outside of normal subfertility
What are other physiological causes of an elevated prolactin, that isn’t prolactinoma? (3)
pregnancy/breastfeeding
stress: exercise, seizure, venepuncture
nipple/chest wall stimulation
What are other pathological causes of elevated prolactin, that isn’t prolactinoma? (3)
primary hypothyroidism
PCOS
chronic renal failure - kidneys don’t excrete prolactin properly
What are other iatrogenic (drug) causes of an elevated prolactin, that isn’t prolactinoma? (5)
antipsychotics selective serotonin re-uptake inhibitors anti-emetics high dose oestrogen opiates ---> mental health drugs affect dopaminergic system
What does physiological cause mean?
Something that happens naturally in the body
What is the release pattern of prolactin ?
none, (not diurnal, or pulsatile, or affected by food)
What are the two causes of high prolactin, without symptoms, not caused by prolactinoma?
- Macroprolactin
2. stress of venopuncture
What has to be done before diagnosing macroprolactin or stress venepuncture?
confirm elevation in serum prolactin, check if no clinical features consistent with this, review medication list
What is macroprolactin?
majority of circulating porlactin is monomeric & biologically active
macroprolactin is ‘sticky’ prolactin:
- a ploymeric form of prolactin
- an antigen-antibody complex of monomeric prolactin and IgG (normally <5% of circ. prolactin)
-limited bioavaliability and bioactivity
–> can reassure patient
How to confirm stress of venepuncture?
exclude by a cannulated prolactin series
- sequential serum measurement 20 mins apart with an indwelling cannula to minimise stress
If elevation of prolactin is true, what next test should be done?
Pituitary MRI –> look for prolactinoma
What is the first line treatment for prolactinoma?
Cabergoline - Dopamine receptor agonist (medical not surgical)
Aims to normalise serum prolactin& shrink prolactinoma
Safe in pregnancy
How do we adjust the dose of dopamine receptor agonists for prolactinoma treatment?
based on size of tumour;
microprolactinoma will need smaller doses than macroprolactinoma
Why do dopamine receptor agonists reduce prolactin levels?
When dopamine binds to the D2 receptors on an anterior pituitary lactotroph, it inhibits the production of prolactin.
Dopamine receptor agonists acts like dopamine and binds to D2 receptor
Prevents lactotrophs from making prolactin
Whats the difference between gigantism and acromegaly?
gigantism is excess GH before growth plates close so affect height.
excess GH after growth plates close = acromegaly (and no excess height)
Why does acromegaly present with such big pituitary tumours?
often insidious presentation - mean time from onset of symptoms to diagnosis =10 years
What are the symptoms of acromegaly?
sweatiness headache hypertension impaired glucose tolerence/ diabetes mellitus coarsening of facial features: - macroglossia - prominent nose - large jaw - inc. hand and foot size
What are two ways in which GH affects growth?
GH direct from anterior pituitary to bone/muscle
GH to the liver, causing the liver to secrete Insulin - like Growth factor (IGF-1)
Why is it unhelpful to do a random measurement of GH when trying to diagnose acromegaly?
GH is pulsatile
How do we diagnose acromegaly?
elevated serum IGF-1 –> HIGH
failed supression of ‘paradoxical rise’ in GH following oral glucose load (oral glucose tolerance test)
normal after glucose –> GH falls after glucose load
acromegalic after glucose –> GH rises after glucose load
Why is it important that acromegaly is treated?
Increased cardiovascular risk in untreated acromegaly
What is the first line treatment for acromegaly?
surgical –> trans sphenoidal pituitary surgery
What is the aim for treatement of acromegaly?
aim to normalise serum GH and IGF-1
What can drugs be used for treatment of acromegaly
medical treatment can be used prior to surgery to shrink tumour or if surgical resection incomplete
What are the options for medical treatment of acromegaly?
somatostatin analogues (octreotide) - endocrine cyanide (can cause many problems with gut) Dopamine agaonists (cabergoline) - GH secreteing pituitary tumours frequently express D2 receptors
What hormone is cushings syndrome caused by?
excess cortisol
What are the physical features of cushing syndrome?
red cheeks moon face fat pads (buffalo humps) thin skin easy bruising purple striae (stretch marks) poor wound healing pendulous abdomen proximal myopathy (muscle weakness causing thin arms and legs)
What are the non-physical features of cushing syndrome?
mental changes - depression osteoporosis imparied glucose tolerance (diabetes) hypertension cardiac hypertrophy females: amenorhea, hirsutism males: erectile dysfunction
What are some causes of excess cortisol leading to Cushing’s? (4)
ACTH dependent: pituitary dependent Cushing's disease (pituitary adenoma) ectopic ACTH (lung cancer)
ACTH independent:
adrenal adenoma or carcinoma
taking steroids by mouth (over prescription)
What is the difference between Cushing’s syndrome and Cushing’s disease?
Cushing’s disease caused by corticotroph adenoma
Cushing’s syndrome is the symptoms caused by excess cortisol
How is Cushing’s disease investigated?
- Elevation of 24h urine free cortisol - increase cortisol secretion
- Elevation of late night cortisol (salivary or blood test) - loss of diurnal rhythm
- Failure to supress cortisol after oral dexamethasone (exogenous glucocorticoid) - increased cortisol secretion
What should be done after confirming hypercortisolism to explore the cause of the Cushing’s symptoms?
Measure ACTH,
if low –> look at ACTH independent
if high –> pituitary MRI (cause is ACTH dependent)
How do non-functioning pituiatry adenomas typically present?
visual disturbances (e.g. bitemporal hemianopia)
*don’t secrete any hormones so no hormone symptoms
When can a non-functioning pituitary adenoma cause hormone related symptoms?
Don’t present with symtoms causes by excess hormones
Can present with hypopituitarism and raised serum prolactin, as pituitary is squished and dopamine can’t travel down pituitary stalk from hypothalamus
What is the treatment for non-functioning pituitary adenoma?
Trans-sphenoidal surgery, esp for large tumours causing visual disturbances
