Pituitary Tumours Flashcards
What three characteristics are used to classify tumours?
Radiological
Function
Benign or malignant
Outline how radiological findings (MRI) contribute to tumour classification
Size:
- Microadenoma <1cm (10mm)
- Macroadenoma >1cm (10mm)
Sellar or suprasellar
Compressing optic chiasm or not
Invading cavernous sinus or not
Outline how function contributes to tumour classification
Excess secretion of a specific pituitary hormone, e.g. prolactinoma
No excess secretion of pituitary hormone (Non Functioning Adenoma)
Describe benign or malignant tumour classification
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
Outline the effect of hyperprolactinaemia on the HPG axis
- Prolactin binds to prolactin receptors on kisspeptin neurons in hypothalamus -> Inhibits kisspeptin release
- This decreases in downstream GnRH/LH/FSH/T/Oest
- Oligo-amenorrhoea/Low libido/Infertility/Osteoporosis
Describe the effect of prolactin on GnRH pulsatility
Flattens it
What is the commonest functioning pituitary adenoma?
Prolactinoma
Describe serum prolactin levels in a person with a prolactinoma
Usually serum [prolactin] >5000 mU/L
Serum prolactin proportional to tumour size
What are the symptoms of a prolactinoma?
Menstrual disturbance
Erectile dysfunction
Reduced libido
Galactorrhoea
Subfertility
What are some physiological causes of an elevated prolactin?
Pregnancy/breastfeeding
Stress: exercise, seizure, venepuncture
Nipple/chest wall stimulation
What are some other pathological causes of an elevated prolactin?
Primary hypothyroidism
Polycystic ovarian syndrome
Chronic renal failure
What are some iatrogenic causes of an elevated prolactin?
Antipsychotics
Selective serotonin re-uptake inhibitors
Anti-emetics
High dose oestrogen
Opiates
When should a pituitary MRI be organised during the investigation of a suspected prolactinoma?
Once you have confirmed a true pathological elevation of serum prolactin
Is the first-line treatment of a prolactinoma surgical?
No it is medical
How are prolactinomas treated and how does this differ depending on size?
Dopamine receptor agonists, e.g. Cabergoline (bromocriptine)
Aim is to normalise serum prolactin & shrink prolactinoma (act on D2 receptors)
Microprolactinomas will need smaller doses than macroprolactinomas
Are dopamine receptor agonists safe to use in pregnancy?
Yes
How would you describe the onset of acromegaly?
Often insidious presentation – mean time to diagnosis from onset of symptoms = 10y
What are the symptoms of acromegaly?
Sweatiness
Headache
Coarsening of facial features
Macroglossia
Prominent nose
Large jaw - prognathism
Increased hand and feet size
Snoring & obstructive sleep apnoea - growth of soft tissue in larynx
Hypertension
Impaired glucose tolerance/diabetes mellitus
What are the mechanisms of growth hormone action?
Growth hormone is released from the somatotrophs of the anterior pituitary and stimulates growth and development in body tissues.
GH also stimulates the liver to produce Insulin-like Growth Factor (somatomedin) - has GH-like effects.
Why is a random GH measurement not useful in the diagnosis of acromegaly?
GH is pulsatile
How is acromegaly diagnosed?
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 GH excess is confirmed, pituitary MRI is done to visualise pituitary tumour
Why shouldn’t acromegaly be left untreated?
There is an increased cardiovascular risk
How is acromegaly treated?
First-line treatment is surgical – trans-sphenoidal pituitary surgery
Aim to normalise serum GH and IGF-1
Radiotherapy - slow
What medications can be used prior to surgery to shrink a tumour or if the surgical resection is incomplete in acromegaly?
Somatostatin analogues e.g., octreotide – ‘endocrine cyanide’ (can switch off other hormones, e.g. CCK)
Dopamine agonists e.g., cabergoline (GH secreting pituitary tumours frequently express D2 receptors)
Why does Cushing’s syndrome occur?
Occurs due to an excess of cortisol or other glucocorticoid
What causes Cushing’s syndrome?
ACTH independent:
- Taking steroids by mouth (common)
- Adrenal adenoma or carcinoma
ACTH dependent:
- Pituitary dependent Cushing’s disease (pituitary adenoma)
- Ectopic ACTH (lung cancer)
What is the difference between Cushing’s Disease and Cushing’s syndrome?
Cushing’s syndrome - excess cortisol
Cushing’s disease is due to a corticotroph adenoma secreting ACTH
What investigations are used for the diagnosis of 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
Once hypercorticolism is confirmed in the investigation of Cushing’s Disease, what should you do?
Measure ACTH
If ACTH is high, do a pituitary MRI - ACTH dependent cause
How are non-functioning pituitary tumours different from functioning tumours and what do they normally present with?
Don’t secrete any specific hormone
Often present with visual disturbance (bitemporal hemianopia)
Can also present with hypopituitarism
Serum prolactin can be raised (dopamine can’t travel down pituitary stalk from hypothalamus)
How are non-functioning pituitary tumours treated?
Trans-sphenoidal surgery needed for larger tumours - particularly if there is visual disturbance
