Pituitary Tumours Flashcards
What cells are in the anterior pituitary and what hormones do they produce?
Somatotrophs- growth hormone (somatotorophin)
Lactotrophs- prolactin
Thyrotrophs- Thyroid stimulating hormone (TSH)
Gonadotrophs- LH and FSH
Corticotrophs- Adrenocorticotropic hormone
What functioning pituitary tumours can form in the anterior pituitary cells ?
Somatotrophs- acromegaly Lactotrophs- Prolactinoma Thyrotrophs- TSHoma Gonadotrophs- Gonadotropinoma Corticotrophs- Cushings disease (corticotroph adenoma)
How is a pituitary tumour appear radiologically (MRI) ?
Size:
- Microadenoma <1cm (10mm)
- Macroadenoma >1cm (10mm)
Sellar (pituitary found within sellar turcica) or suprasellar (above the sellar)
Compressing optic chiasm or not
Invading cavernous sinus or not
What is the function of a pituitary tumour?
Excess secretion of a specific pituitary hormone
eg prolactinoma
If there’s no excess secretion of pituitary hormone its called non Functioning Adenoma
What type of pituitary tumour is rare?
Pituitary carcinoma very rare (<0.5% of pituitary tumours)
How is mitotic index of pituitary tumor measured?
Mitotic index measured using Ki67 index – benign is <3%
What happens in hyperprolactinemia?
- Hypothalamus: Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
- Inhibits kisspeptin release.
- Ant. pituitary gland: Decreases in downstream GnRH/LH/FSH/T/Oest
- Gonads: Oligo-amenorrhoea/Low libido/Infertility/Osteoporosis
What is a prolactinoma?
Commonest functioning pituitary adenoma
Usually serum [prolactin] >5000 mU/L
Serum [prolactin] proportional to tumour size (more prolactin, bigger the tumour)
How does a prolactinoma present?
Menstrual disturbance Erectile dysfunction Reduced libido Galactorrhoea (production of milk outside of pregnancy) Subfertility
What are other causes of elevated prolactin?
Physiological
- Pregnancy/breastfeeding
- Stress: exercise, seizure, venepuncture
- Nipple/chest wall stimulation
Pathological
- Primary hypothyroidism
- Polycystic ovarian syndrome
- Chronic renal failure
Iatrogenic
- Antipsychotics
- Selective serotonin re-uptake inhibitors
- Anti-emetics
- High dose oestrogen
- Opiates
Is there an elevation in prolactin throughout the day?
It has no diurnal variation
It is possible to get lots of false positives for elevated prolactin so confirm the true elevation
If a patient has no clinical features consistent with a prolactinoma what other possible options are there?
Macroprolactin or stress of venepuncture
What is macroprolactin?
Majority of circulating prolactin is monomeric & biologically active
Macroprolactin is ‘sticky prolactin’ (a polymeric form of prolactin)
An antigen–antibody complex of monomeric prolactin and IgG forms (normally <5% of circulating prolactin)
This can be recorded on assay as elevation of prolactin – needs alternative method to confirm
You should reassure the patient that their prolactin levels are normal
How can stress of venepuncture cause elevated prolactin?
Increased stress can cause an increase in prolactin
In order to eliminate this factore sequential serum prolactin measurements should be taken 20 mins apart with an indwelling cannula to minimise venepuncture stress
What should you do when you have confirmed true elevation of serum prolactin?
Organise a pituitary MRI
What is the first line treatment for a prolactinoma?
First-line treatment is medical not surgical
Dopamine receptor agonists is the main treatment (e.g. Cabergoline (bromocriptine))
Its safe in pregnancy
The aim is to normalise serum prolactin & shrink prolactinoma
How should medication be adjusted for a microprolactinoma vs macroprolactinoma?
Microprolactinomas will need smaller doses than macroprolactinomas
How do dopamine receptor agonists work?
The agonist binds to the D2 receptor on anterior pituitary lactotroph suppressing the release of prolactin
What does a pituitary tumour secreting excess GH cause?
Gigantism in children (grow tall)
Acromegaly in adults (don’t grow taller because epiphyseal plates have fused)
What are symptoms of acromegaly?
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 mean time to diagnose from onset of acromegaly symptoms?
10 years
What is the mechanism of GH action?
Anterior pituitary releases GH which acts on liver causing elevated levels of IGF-1 and IGF-2 to be produced
GH and IGF-1 act on body tissues causing growth and development
How is acromegaly diagnosed?
GH is pulsatile so measuring it is unhelpful Instead glucose (75g oral load) is given. If the patient has acromegaly there will be a paradoxical rise in GH (in a healthy patient GH falls after glucose given)
What scan should be carried out after confirmation of GH excess?
MRI to visualise pituitary tumour
How is acromegaly treated?
- First-line treatment is surgical – trans-sphenoidal pituitary surgery
The aim to normalise serum GH and IGF-1 - We can use medical treatment prior to surgery to shrink tumour or if surgical resection incomplete
E.g. Somatostatin analogues eg octreotide – ‘endocrine cyanide’
Dopamine agonists eg cabergoline (GH secreting pituitary tumours frequently express D2 receptors) - Radiotherapy (slow)
What causes cushing’s syndrome?
Occurs due to an excess of cortisol or other glucocorticoid
Causes include:
- Taking steroids by mouth (common)
- Pituitary dependent Cushing’s disease (pituitary adenoma)
- Ectopic ACTH (lung cancer)
- Adrenal adenoma or carcinoma
How can we categorize causes of cushing’s syndrome?
The causes can be catagorised as ACTH dependent or independent:
ACTH dependent:
- Cushing’s disease (corticotroph adenoma)
- Ectopic ACTH (lung cancer)
ACTH independent
Taking steroids by mouth (common)
Adrenal adenoma or carcinoma
What is the difference between cushing’s syndrome and cushing’s disease?
Cushing’s syndrome = excess cortisol
Cushing’s disease is due to a corticotroph adenoma secreting ACTH
How would we diagnose cushing’s disease?
We’d expect an elevation of 24 hour urine free cortisol (increased cortisol secretion)
There would also be an elevation of late night cortisol (salivary or blood test) indicating a loss of diurnal rhythm
We can also give patient oral dexamethasone (exogenous glucocorticoid). Failure to suppress this indicates cushing’s disease
What should be tested once we have confirmed hypercortisolism in cushing’s disease?
Once confirmed hypercortisolism, measure ACTH
If ACTH high, pituitary MRI ACTH dependent
What are features of a non-functioning pituitary adenoma?
Don’t secrete and specific hormone
Often present with visual disturbance (bitemporal hemianopia)
Can be present with hypopituitarism
Serum prolactin can be raised (as dopamine cant travel down stalk)
How can large non-functioning pituitary adenomas be treated?
Trans-sphenoidal surgery needed for larger tumours, particularly if visual disturbance
