Pituitary tumours Flashcards
What would a pituitary tumour of somatotrophs cause?
Acromegaly
What would a pituitary tumour of lactotroph cells be called?
Prolactinoma
What would a pituitary tumour of thyrotrophs be called?
TSHoma
What would a pituitary tumour of gonadotrophs be called?
Gonadotrophinoma
What would a tumour of corticotrophs be called?
Cushing’s Disease
What are the three classifications for Pituitary tumours?
Radiological (MRI)
Function
Benign or Malignant
What is determined from the MRI of a pituitary tumour?
- Size Microadenoma <1cm (10mm) Macroadenoma >1cm (10mm) - Sellar or suprasellar - Compressing optic chiasm or not - Invading cavernous sinus or not ( very hard to remove surgically from the cavernous sinus)
What are the functional classifications for a pituitary tumour?
Excess secretion of a specific pituitary hormone
eg prolactinoma
No excess secretion of pituitary hormone (Non Functioning Adenoma)
Are pituitary tumours more likely to be 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
How does hyperprolactinaemia inhibit kisspeptin neurons?
Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus
Inhibits kisspeptin release.
Decreases in downstream GnRH/LH/FSH/T/Oest
Oligo-amenorrhoea/Low libido/Infertility/Osteoporosis
What is the commonest functioning pituitary adenoma?
Commonest functioning pituitary adenoma
Usually serum [prolactin] >5000 mU/L
Serum prolactin is proportional to tumour size
What is the presentation for Prolactinomas?
Menstrual disturbance Erectile dysfunction Reduced libido Galactorrhoea ( very rare in men) 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
What questions would we ask ourselves if we saw someone with an elevated prolactin?
is this a true elevation in serum prolactin?
Prolactin has no diurnal variation, not affected by food.
Red flag would be high serum prolactin with no clinical features.
What would be the 3 possible options if you had a patient with raised prolactin but no clinical features?
False positive
Macroprolactin
Stress of venipuncture
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 (normally <5% of circulating prolactin)
Recorded on assay as elevation of prolactin – needs alternative method to confirm
Limited bioavailability and bioactivity
Can reassure patient
How do you overcome raised prolactin due to stress of venipuncture?
Exclude by a cannulated prolactin series
- Sequential serum [prolactin] measurement 20 mins
apart with an indwelling cannula to minimise
venipuncture stress .
What should you do once you have confirmed a true pathological elevation of prolactin?
Pituitary MRI
How do we 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 agonist work?
D2 receptor agonist, binds to D2 receptor and works like dopamine, prevents prolactin production and shrinks lactotrophs.
What causes Acromegaly?
A pituitary tumour of the somatotrophs making too much growth hormone. Usually presents with big tumours, mainly due to insidious presentation.
What are the presentations 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 are the 2 mechanisms of growth hormone action?
Direct - secreted from the anterior pituitary bing to GH receptors on bone and muscle/soft tissue.
Indirect - travels to the liver and causes IGF-1 secretion.
How is acromegaly diagnosed?
GH 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 & prolactin
Once confirm GH excess, pituitary MRI to visualise pituitary tumour
Why is it necessary to treat Acromegaly?
Increased cardiovascular risk in untreated Acromegaly.
What it the Treatment for Acromegaly?
First-line treatment is surgical – trans-sphenoidal pituitary surgery
Aim to normalise serum GH and IGF-1
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)
Radiotherapy (slow)
What biochemical test confirms acromegaly?
Rise in GH following oral glucose load.
What causes Cushing’s syndrome?
Occurs due to excess cortisol or other glucocorticoid.Causes of Cushing’s syndrome
Taking steroids by mouth (common)
Pituitary dependent Cushing’s disease (pituitary adenoma)
Ectopic ACTH (lung cancer)
adrenal adenoma or carcinoma
What are ACTH dependent causes of Cushing’s syndrome?
Cushing’s disease (corticotroph adenoma) Ectopic ACTH (lung cancer)
What are ACTH independent causes of Cushing’s syndrome?
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
What do we investigate to diagnose 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
What would you do if you confirmed hypercortisolism?
Measure ACTH
If ACTH is high them pituitary MRI, ACTH dependent
What biochemical test would be consistent with Cushing’s disease?
Elevated late night cortisol
What do Non-Functioning pituitary tumours usually effect?
Often present with visual disturbances, Dont secrete any specific hormone.
What are the problems with Non-Functioning Pituitary adenomas?
Can present with hypopituitarism
Serum prolactin can be raised (dopamine can’t travel down pituitary stalk from hypothalamus)
How do you treat Non-Functioning Pituitary adenomas?
Trans-sphenoidal surgery needed for larger tumours, particularly if visual disturbance
