Acromegaly and Prolactinoma Flashcards
When will getting acromegaly make you a giant?
Teenager
Pathogenesis of acromegaly
Pituitary Tumour – releases GH – under influence of GH binding to receptor in liver get release of Insulin like growth factor 1 – this goes on to have systemic efffects
GH in excess causes harm
Is acromegaly common?
No
Incidence of 3.3 per million (range 2.8 to 4.0)
Mean age at diagnosis is 44 years
What are the co-morbidities of acromegaly?
Hypertension and heart disease
High BP
Cerebrovascular events and headache
Strokes
Arthritis
Insulin-resistant diabetes
Sleep apnea
What is the impact of acromegaly on survival?
Affects your LE
However this + diabetes or cardiac disease brings it down exponentially lower
Growth hormone (acromegaly) and survival
As growth hormones level increase survival was lower
IGF one stimulated by GH – fairly stable – increased of this leads to increased mortality
What do we have to check for the diagnosis of acromegaly?
Clinical Features
GH
IGF-I
What are the physical features of acromegaly?
Acral enlargement
Arthralgias
Maxillofacial changes
Excessive sweating
Headache
Hypogonadal symptoms
What are the GH secretion patterns?
Growth hormone is a pulsatile hormone – in normal people theres pulses of GH and then go down to baseline
Acromegaly – GH never returns fully to baseline
What is the oral glucose tolerance test for the diagnosis of acromegaly?
Normal – give them glucose it suppresses GH
Acromegaly don’t get suppression – get rise instead (most of the time) dont get suppression
What is the criteria for the diagnosis of acromegaly?
Acromegaly excluded if:
random GH <0.4 ng/ml and normal IGF-I
If either abnormal proceed to:
75 gm Glucose tolerance test (GTT)
Acromegaly excluded if:
IGF-I normal and
GTT pushes GH down
What are the options for treatment for acromegaly?
Pituitary surgery
Medical therapy
Radiotherapy
Why is surgery a good option for acromegaly?
Causes rapid fall of GH
Decompression
Cost effective
Prospective cure
Surgery rates
For a microadenoma <1cm 90% success rate
For a macroadenoma >1cm <50cm success rate
Depends on surgeon and size of tumour
Whats transsphenoidal pituitary surgery?
Used as primary treatment for all types of pituitary adenoma except prolactinoma
Problems making surgery harder
Large size
Invasiveness
Life-long monitoring needed for most patients
How does conventional radiotherapy work for acromegaly?
multi-fractional
Optic chiasm doesn’t like radiotherapy
Fraction – small dose daily for 5-6 weeks – irradiates tumour – minimise the dose of optic chiasm – this is conventional
Stereotactic – focusing radiotherapy to make sure it misses vital structures
What is stereostatic radiotherapy?
single fraction
less radiation to surrounding tissues
gamma knife
LINAC
proton beam
Gamma knife – 200 fine beams to hit a target
What are the possible issue of pituitary radiotherapy?
- Loss of pituitary function in the long-term
- Potential damage to local structures – e.g. eye nerves
- Control of tumour growth / excess hormone
secretion not always achieved - Life-long monitoring needed for all patients
What are the disadvantages of convential radiotherapy?
- Delayed response
- Hypopituitarism
- Rare secondary tumours
- rare visual defects
- Long time to take its effects
Deficiency at 10 years:
TSH 19%
ACTH 38%
gonadotrophin 55%
What does the medical therapy consist of?
Dopamine agonists – cabergoline
Somatostatin analogues
Growth Hormomne receptor antagonist
What do pituitary tumours express?
Tumours express D2 receptors – G protein coupled cell surface receptors and under influence of dopamine will switch off GH
What do dopamine agonists do?
Control normal IGF-1
bromocriptine 10%
Cabergoline 37%
more potent
fewer side effects
twice weekly
Particularly useful in GH/prolactin co-secreting tumors
occasional dramatic tumour shrinkage
control of GH secretion
What are the advantages of dopamine agonists (medical therapy)?
No hypopituitarism
Oral administration
Rapid onset
What are the disadvantages of dopamine agonists (medical therapy)?
Relatively ineffective
Side effects
Somatostatin
Endogenous hormone
Short half life
Hormone cyanide – switches off production of many diff hormones
Subtype 2 typically present on growth hormone secreting tumours that cause acromegaly
binds all 5 receptor sub-types
Somatostatin analogues
Octreotide
more specific
T1/2 100 min
no rebound
Lanreotide
Both of these share same business end of molecule compared to somatostatin
Disadvantages of somatostatin analogues
injectable
side effects
Pegvisomant
GH analogue
191 amino acids
9 amino acid substitutions
4 - 5 PEG moieties
molecular weight 42 - 46000 D
half-life >70 hours
subcutaneous administration
serum GH cannot be used as a disease marker
What is the physiology of pegvisomant?
GH binds to cytokine receptor – binds at site 1 – site 2 causes dimerization to have this dimer that then signals allow GH in liver to cause creation of IGF 1 and signalling Mutation which at site 2 prevents the dimerization and some mutation in site 1 to make it more avidly bind to GH receptor – pegalation molecules added to it so it doesn’t clear as quickly – works as competitive antagonist
Pegvisomant results
Very good
97% normalisation of IGF-1
Prolactinoma features
Incidence 10 per 100,000
Women»_space; men
Prevalence 90 per 100,000
Lactotroph cell tumour of the pituitary
What are the clinical features of microadenoma
headache
visual field defect (bi-temporal hemianopia)
CSF leak (rare)
What are the clinical features of the effect of prolactin?
menstrual irregularity/amenorrhoea
infertility
Galactorrhoea
low libido
low testosterone in men
High levels of prolactin interferes with gonadotrophin releasing hormone pulsatitlity and switches off synchronised release of FSH and LH
Galactorrhoea – milk from nipple
Hyperprolactinaemia features:
Macroprolactinoma – can be massive
Microprolactinoma – virtually always stay small
Non functioning pituitary tumour – compression of pituitary stalk – prolactin <4000 mIU/L
Antidopaminergic drugs – don’t measure prolactin in patients on these, but a careful drug history needed!
What is the management of prolactinoma
Medical rather than surgery
Dopamine agonists – cabergoline, bromocriptine, quinagolide
Remarkable shrinkage usual with macroadenoma – sight saving
Microadenoma - usually respond to small doses of cabergoline just once or twice per week
