Acromegaly Flashcards
acromegaly
due to increased secretion of growth hormone from a GH secreting pituitary tumour (99%) or hyperplasia
GH secretion
pulsatile, peaks during sleep
effects of GH on growth
- GH and IGF-1 stimulates proliferation of chondrocytes resulting in bone growth
- IGF-1 stimulate both the differentiation and proliferation of myoblasts and stimulates amino acid uptake and protein synthesis = muscle growth
- GH stimulates skeletal and soft tissue growth, therefore produce gigantism in children (if acquired before epiphyseal fusion) and acromegaly in adults
metabolic effects of GH
- GH directly and through IGF-I stimulates osteoblast proliferation and activity, promoting bone formation. It also stimulates osteoclast differentiation and activity, promoting bone resorption. The result is an increase in the overall rate of bone remodelling, with a net effect of bone accumulation.
- Protein metabolism: stimulates protein anabolism
- Fat metabolism: enhances use of fat by stimulating triglyceride breakdown and oxidation in adipocytes
- Carbohydrate metabolism: supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver. Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia.
control of GH secretion
- GHRH
- Somatostatin inhibits GH in response to GHRH and other stimulatory factors such as low blood glucose concentration
- Produced from the delta cells of the pancreas, pylorus and duodenum
- Ghrelin (‘hunger hormone’) stimulates GH secretion
- GH secretion is also part of a negative feedback loop involving IGF-1
what does increased GH cause in children and adults
gigantism in children (if acquired before epiphyseal fusion) and acromegaly in adults.
clinical features
- giant
- thickened soft tissue - skin, large jaw, sweaty large hands
- hypertension and cardiac failure
- snoring/obstructive sleep apnoea
- headaches
- DM
- local pituitary effects: visual fields and hypopituitarism
what is the snoring/OBSA due to
enlargement of pharyngeal tissue
what are headaches due to
- effect of blood vessel swelling (not tumour) and produce a migrainous type headache
- Often relieved immediately by treatment
- can be v severe
reason for DM
- GH is a stress hormone and causes an increase in BG
- GH supresses the abilities of insulin to stimulate uptake of glucose in peripheral tissues and enhance glucose synthesis in the liver - increased blood glucose
- Somewhat paradoxically, administration of growth hormone stimulates insulin secretion, leading to hyperinsulinemia
what is one at risk of
early CV death
what is there a risk of developing in the colon
colonic polyps and colon cancer
somatostatin effect on GH
may be in reponse to low BG
diagnosis
- diagnostic: GTT
- IGF-1 - age and sex matched
- visual field
- CT/MRI scan of pituitary fossa
- pituitary function test for other hormones
OGTT
- BG levels are raised in the patient by giving them a sugary drink after a period of fasting, this should suppress GH levels
- normally, GH suppressed to <0.4ug/L
- in acromegaly GH will be unchanged - this is diagnostic
- dont rely on random GH as secretion is pulsatile and during peaks acromegalic and normal levels overlap
IGF-1 for diagnosis
- Age and sex matched
- May be used as a screening test and is sometimes used to monitor disease
management
pituitary surgery (trans-sphenoidal) is often first line
what must be done after surgery
resest GTT
- GH <0.4ug/L is clinically satisfactory
- GH >1ug/L requires drug therapy (start with somatostatin analogues)
treatment outcomes of pituitary surgery
90% if microadenoma
50% if macroadenoma
somatostatin analogues
- Reduce GH in most patients and cause tumour shrinkage (30-50% decrease in size, takes 6-12 months)
- Can be used as an adjunct to surgery: they are used pre-op to rapidly relieve headaches and improve the outcome.
adverse effects of somatostatin analogues
- Local stinging
- Short term, reflect effects on gut motility
- Flatulence
- Diarrhoea
- Abdominal pains
- Long term
- Gastritis
- Gallstones
- Risk of biliary colic
Are causing the gallbladder to not contract as well, occur by 6 months
what are the 3 somatostatin analogues used
- Octreotide (SC) - 3OD
- sandostatin (IM) - once/28days
- lanreotide (IM) - once/28days
dopamine agonists
- Cabergoline up to 3g weekly.
- They are shown to reduce GH to <2ug/L in 15% of patients (minority)
GH antagonist
Pegvisomant
binds to GH receptor and blocks GH activity
how is Pegvisomant adminstered
once daily SC injection of 10-30 mg
when is Pegvisomant used
- last line in therapy
- IGF-1 decreases but serum GH concentrations may increase
- very effective: 85% response rate
- but has no effect on tumour size (may increase tumour size)
follow up of pituitary surgery
- achieve clinically safe levels of GH and IGF-1
- check other pituitary hormones
- cancer surveillance
- CV risk factors - check BP, lipids , glucose
- sleep apnoea
what are the clinically safe levels of GH post - treatment
GH <0.4 ug/L post GTT
GH <2 ug/L random
