Pituitary Tumours Flashcards
Functioning pituitary tumours
Acromegaly Prolactinoma TSHoma Gonadotrophinoma Cushing’s disease (corticotroph adenoma)
Pituitary tumour classification
Radiological (MRI) Size Microadenoma <1cm (10mm) Macroadenoma >1cm (10mm) Sellar or suprasellar Compressing optic chiasm or not Invading cavernous sinus or not
Function
Excess secretion of a specific pituitary hormone
eg 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
Kisspeptin
Hyperprolactinaemia
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
Prolactinomas
Commonest functioning pituitary adenoma
Usually serum [prolactin] >5000 mU/L
Serum [prolactin] proportional to tumour size
Presentation Menstrual disturbance Erectile dysfunction Reduced libido Galactorrhoea Subfertility
Pregnancy/breastfeeding Stress: exercise, seizure, venepuncture Nipple/chest wall stimulation Primary hypothyroidism Polycystic ovarian syndrome Chronic renal failure Antipsychotics Selective serotonin re-uptake inhibitors Anti-emetics High dose oestrogen Opiates
‘true’ elevation in serum prolactin
No diurnal variation, not affected by food
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
Stress of venepuncture
Exclude by a cannulated prolactin series
Sequential serum [prolactin] measurement 20 mins apart with an indwelling cannula to minimise venepuncture stress
Investigation of prolactinoma
pituitary MRI
Treatment of prolactinoma
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
Anterior pituitary lactotrophs contain D2 receptors which inhibit prolactin production
Cabergoline works like dopamine to inhibit prolactin production by binding to D2 receptors
Excess GH
Gigantism = children Acromegaly = adults
Acromegaly
Often insidious presentation – mean time to diagnosis from onset of symptoms = 10y
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
Mechanisms of growth hormone action
Direct effect by binding to growth receptors on bones
Also travel to liver where it tells liver to secret insulin like growth factor 1 and 2
Diagnosis of acromegaly
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
Treatment of acromegaly
Increased cardiovascular risk in untreated 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)
Cushing’s syndrome
Fat pads (buffalo hump) Moon face Easy bruising Purple Striae (stretch marks) Thin skin Proximal myopathy (muscle weakness) Poor wound healing Hypertension and hypokalaemia
Occurs due to an excess of cortisol or other glucocorticoid
Causes of Cushing’s syndrome
Taking steroids by mouth (common) - ACTH independent
Pituitary dependent Cushing’s disease (pituitary adenoma) - ACTH dependent
Ectopic ACTH (lung cancer) - ACTH dependent
adrenal adenoma or carcinoma - ACTH independent
Investigation 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 confirmed hypercortisolism, measure ACTH
If ACTH high, pituitary MRI ACTH dependent
