physiology of growth hormone secretion W7

Question 1

name for cells which secrete growth hormone?

Answer 1

somatotrophs

Question 2

where are somatotrophs found?

Answer 2

somatotrophs are found in the anterior pituitary (comprise 35-45%)

Question 3

name of disorder of excess GH production

Answer 3

acromegaly

Question 4

growth hormone axis?

Answer 4

hypothalamus releases GHRH, acts on pituitary which releases GH. GH predominantly acts on the liver, stimulates release of IGF-1.

Question 5

IGF-1 stands for?

Answer 5

insulin-like growth factor 1

Question 6

key inhibitory factor? where is this released?

Answer 6

SRIF (somatostatin) released from hypothalamus
also known as GHIH (growth hormone inhibiting hormone)

Question 7

which area of the hypothalamus is growth hormone released from

Answer 7

preoptic area

Question 8

GHRH receptors pathway?

Answer 8

G protein coupled receptor. increases adenylate cyclase which increases cAMP which increases intracellular calcium, causing release of growth hormone and increase in growth hormone mRNA transcription

Question 9

what is GHRH receptors enhanced by

Answer 9

oestradiol
ghrelin
glucocorticoids
starvation

Question 10

what is GHRH receptors blunted by

Answer 10

somatostatin
obesity
insulin
glucose
increased age

Question 11

ghrelin features

Answer 11

orexigenic (enhances food consumption)
produced in stomach (particularly in fasting and pre-meal state)
enhances GH secretion
maintains blood glucose levels during starvation

Question 12

somatostatin features

Answer 12

released from PVN of hypothalamus
peptide hormone
acts on 5 different G-protein coupled receptors
suppressive effect on multiple pituitary hormones (including GH and TSH) and insulin

Question 13

where is growth hormone receptor most dominantly expressed

Answer 13

liver!

Question 14

GHR intracellular signalling type? what does it stimulate?

Answer 14

phosphorylation cascade
hepatic IGF-1 synthesis and secretion

Question 15

IGF-1 features?

Answer 15

responsible for most linear growth-promoting activities of GH
99% is protein bound
mainly produced in liver
IGF-1 receptor present across multiple tissues
ligand binding -> TK activity -> IRS-1 pathway

Question 16

physiologic stimulatory factors for GH

Answer 16

exercise
stress
physical
psychologic
slow-wave sleep
fasting

Question 17

physiologic inhibitory factors for GH

Answer 17

hyperglycaemia
elevated free fatty acids
elevated IGF-1
REM sleep
senescence, aging

Question 18

pathological stimulatory factors for GH

Answer 18

renal failure
cirrhosis
type 1 diabetes

Question 19

pathological inhibitory factors for GH

Answer 19

obesity
hypothyroidism
hyperthyroidism

Question 20

pattern of GH secretion?

Answer 20

pulsatile - reductions in tonic inhibition by somatostatin
diurnal - 2/3 secreted at night with onset at slow wave sleep
peaks at puberty, falls with ageing

Question 21

growth hormone actions?

Answer 21

direct and indirect (via IGF-1) action on epiphyseal growth plates to stimulate linear growth
increases lipolysis and lipid oxidation (mobilization of stored TG)
stimulates protein synthesis
antagonism of insulin action
phosphate, water and sodium retention

Question 22

IGF-1 actions?

Answer 22

decrease blood glucose/improve insulin sensitivity
stimulate whole body protein synthesis, inhibit proteolysis
reverse catabolic effects of glucocorticoids on protein synthesis
anabolic effect on bone
negative feedback on GH release

Question 23

laron syndrome?

Answer 23

mutations in GHR
normal/high GH, low GH-binding protein, low IGF-1
postnatal growth failure
small head circumference, saddle nose, prominent forehead, delayed skeletal maturation, osteopenia and obesity
reduced cancer susceptibility

Question 24

GH deficiency in children?

Answer 24

severe growth failure
treat with recombinant growth hormone when epiphyses are open
monitor IGF-1 levels during treatment, continue until linear growth complete then retest for GH deficiency

Question 25

GH deficiency in adults - diagnostic tests?

Answer 25

IGF-1 lower than reference range confirms diagnosis in adults with pituitary disease
stimulatory tests (GHRH-arginine)

Question 26

GH replacement in adults is associated with what?

Answer 26

increased muscle mass, decreased body fat, increased exercise capacity, increased bone mineral density in men, increase in some parameters of cardiac function

Question 27

is GH replacement recommended in adult onset GH deficiency?

Answer 27

GHR recommended against because evidence not strong and potential adverse consequences often outweigh potential benefits

Question 28

acromegaly features?

Answer 28

delay from symptoms to diagnosis is 12 years (very rare condition)
75% due to somatotroph macroadenomas in pituitary

Question 29

macroadenoma?

Answer 29

tumour greater than 1cm

Question 30

acromegaly presentation?

Answer 30

headache
enlargement of lips, nose, tongue
cardiomyopathy
CVD
prognathism (growth of lower jaw)
increased sweating
thicker skin
hypertension
enlargement of liver
type 2 diabetes risk
colon cancer risk
enlargement of hands
carpal tunnel syndrome
myopathy
arthropathy
enlargement of feet

Question 31

acromegaly diagnosis?

Answer 31

test in those with classical clinical features, clusters of associated features, and those with pituitary adenoma

measure IGF-1, if equivocal do oral glucose tolerance test, if elevated then acromegaly is confirmed in patients with clinical manifestations, if normal then rule out acromegaly

Question 32

acromegaly treatment?

Answer 32

pituitary surgery (removal of adenoma) as first line
somatostatin analogues to inhibit GH release (lanreotide)
GHR antagonist (pegvisomant)
pituitary radiotherapy