Basic Principles Flashcards
what is ACTH?
adrenocorticotrophic hormone
what gland produces adrenocorticotrophic hormone (ACTH)?
anterior pituitary
what is the function of adrenocorticotrophic hormone (ACTH)?
stimulates the adrenal cortex to synthesise and release cortisol
what does anti-diuretic hormone (ADH) do to the concentration of urine?
increases the concentration
what type of target cells are involved in endocrine signalling?
distant target cell
what type of target cells are involved in autocrine signalling?
acting on itself
what type of target cells are involved in paracrine signalling?
surrounding (local) cells
what are the 3 main classes of hormones?
- (glyco)proteins and peptides
- steroids
- tyrosine and tryptophan derivatives
what molecule are steroids derived from?
cholesterol
what type of hormone is oxytocin?
protein/peptide
what type of hormone is cortisol?
steroid
what type of hormone is aldosterone?
steroid
what type of hormone is adrenaline or epinephrine?
tyrosine/tryptophan derivatives
what type of hormones are the thyroid hormones?
tyrosine derivatives
what type of hormone is insulin?
protein/peptide
what type of hormone is testosterone?
steroid
are amines pre-synthesised and stored or synthesised on demand?
pre-synthesised and stored
where are amines stored?
intracellular vesicles
what is the exocytosis of vesicles concentrated with amine hormones dependent on?
Ca2+ influx caused by a stimuli
calcium dependent exocytosis
are peptide/protein hormones pre-synthesised and stored or synthesised on demand?
pre-synthesised and stored
where are proteinpeptide hormones stored?
intracellular vesicles
what is the exocytosis of vesicles concentrated with protein/peptide hormones dependent on?
Ca2+ influx caused by a stimuli
calcium dependent exocytosis
are peptide hormones hydrophilic or hydrophobic?
hydrophilic
are amine hormones hydrophilic or hydrophobic?
hydrophilic
how are amine hormones transported in the plasma?
free
how are protein/peptide hormones transported in the plasma?
free
in the first stage of production of a steroid hormone, what is cholesterol converted into?
pregnenolone
what is the rate limiting step in the production of a steroid hormone from cholesterol?
conversion of cholesterol to pregnenolone
where does the conversion of cholesterol to pregnenolone occur?
mitochondrial membrane
where are steroid hormones stored?
they aren’t stored within the cell, as soon as they are made they are released directly into the blood stream
why is there a slow time frame of steroid hormone action?
because it depends on synthesis and release of a new hormone and not just release of a pre-existing hormone
how are steroid hormones transported in the plasma?
bound to a carrier protein
what are the 2 functions of a carrier protein in the transportation of hormone?
- increase amount transported in blood
2. prevent rapid excretion by preventing filtration at the kidney
what amine hormones needs to be transported in the bloodstream bound to a carrier protein because it is relatively insoluble in plasma?
thyroid hormones
what is the important carrier protein specific to cortisol?
cortisol-binding globulin
apart from cortisol, what hormone does cortisol-binding globulin also transport?
some aldosterone
what is the important carrier protein specific to thyroxine (T4)?
thyroxine-binding globuline
apart from thyroxine, what hormone does thyroxine-binding globulin also transport?
some triiodothyronine (T3)
what is the important carrier protein specific to testosterone and estradiol?
sex steroid-binding globulin
when are the levels of cortisol in the body highest and when are they lowest?
highest- 9/10am
lowest- 12am
(diurnal rhythm)
when are the levels of testosterone in the body highest?
first thing in the morning
what are the 3 main types of hormone receptor?
- g-protein coupled
- receptor kinases
- nuclear receptors
what type of hormones activate g-protein coupled receptors?
amines and some proteins/peptides
what type of hormones activate receptor kinases?
proteins/peptides
what are the 3 subclasses of nuclear receptors?
class 1 class 2 hybrid class
what is the difference between class 1 and class 2 nuclear receptor?
class 1- in the absence of hormone, located within the cytoplasm, move to nucleus once activated by hormone class 2- always present in the nucleus, hormone has to diffuse into nucleus to have it's effect
what are class 1 nuclear receptors bound to when in the cytoplasm?
inhibitory heat shock proteins
what type of hormones activate class 1 nuclear receptors?
mainly steroids
what type of substance activate class 2 nuclear receptors?
lipids
what type of receptor does insulin signal via?
tyrosine kinase receptor
once the receptor steroid complex (class 1 nuclear receptor) moves to the nucleus, it forms a dimer. what does this dimer bind to within the DNA?
hormone response elements
what endogenous substance might make urine red or red/brown?
haemoglobin
myoglobin
what endogenous substance might make urine smokey red?
intact RBC
what endogenous substance might make urine yellow and frothy when shaken?
bilirubin
what inborn error of metabolism makes urine brown-black on standing?
alkaptonuria
due to homogentisic acid
what does leucocyte presence in urine indicate?
UTI
what does urobilinogen presence in urine indicate?
a normal finding
increased urobilinogen might indicate liver abnormalities or excessive destruction of RBCs (eg haemolytic anaemia)
what is the normal pH of urine?
5-6
5.5 average
when are pH values for urine at their lowest?
after overnight fast
when are pH values of urine at their highest?
after meals
what may a strongly acidic urine pH indicate?
uncontrolled diabetes
starvation
dehydration
what may an alkaline urine pH of >8 indicate?
stale sample
UTI
what does specific gravity of urine assess?
the concentration and diluting power of the kidneys
what does the presence of bilirubin in urine indicate?
hepatic or biliary disease
what does the presence of nitrites in urine suggest?
UTI
what type of bacteria causing UTIs cause the presence of nitrites in urine and why?
gram negatives
convert dietary nitrates into nitries
what main 5 diagnoses does the persistent presence of protein in urine suggest?
renal disease UTI hypertension pre-eclampsia congestive heart failure
what does the presence of blood in urine suggest?
serious renal or urological disease
UTI
what does the presence of ketones in urine suggest?
starvation
uncontrolled diabetes
what are the 5 main causes of glucose in urine?
uncontrolled diabetes stress cushings syndrome post-general anaesthetic acute pancreatitis
(because of either increased blood glucose levels or reduced renal glucose absorption)
if not tested within one hour of collection, where should urine be stored?
refrigerator
where should the urine reagent strips be stored?
a cool, dry place
do not put in refrigerator
are acinar cells the exocrine or endocrine part of the pancreas?
exocrine
what cells secrete insulin?
pancreatic beta cells
found in pancreatic islets
what cells secrete glucagon?
pancreatic alpha cells
found in pancreatic islets
compare glucagon and insulin in terms of effect on hepatic glucose output? (gluconeogenesis)
insulin decreases gluconeogenesis
glucagon increases gluconeogenesis
what secretes somatostatin?
pancreatic delta cells
found in pancreatic islets
what organelle synthesise preproinsulin? (the larger single chain preprohormone of insulin)
rough endoplasmic reticulum
what type of insulin was used before human insulin?
bovine insuline
what transporter does glucose enter pancreatic B cells via?
GLUT 2
once inside a pancreatic B cell, what enzyme phosphorylates the glucose?
glucokinase
once inside a pancreatic B cell, what does glucokinase convert glucose into?
glucose-6-phosphate
what happens to the pancreatic beta cell intracellular ATP concetration as the metabolism of glucose increases?
ATP concentration increases
how many molecules of ATP are produced after oxidative phosphorylation of one glucose molecule?
36
what does ATP within the pancreatic beta cell do to the ATP-sensitive K+ channels? and what does this cause?
ATP inhibits the ATP-sensitive K+ channels
prevents K+ efflux
therefore cause depolarisation of the beta cell membrane
inhibition of K+ efflux within the pancreatic beta cell cause depolarisation of the beta cell membrane, what does this result in?
opening of voltage-gated Ca2+ channels
what does an increase of intracellular calcium within the pancreatic beta cell cause?
fusion of the secretory vesicles with the cell membrane (exocytosis)
–> release of insulin into the bloodstream
how many stages of insulin release are there after glucose is administered orally?
2 stages
biphasic
compare the 2 stages of insulin release?
1st stage: insulin granules immediately available for release from readily releasable pool
2nd stage: reserve pool must undergo preparation reactions to become mobilised and then release
what is the target for sulphonylurea drugs? (in diabetes)
and how does it work?
the sulphonylurea subunit of the ATP-sensitive K channel
inhibits the ATP-sensitive K channel to cause depolarisation
how many proteins make up the ATP-sensitive K channel?
2
what cells must be functioning in order for sulphonylureas to be useful in the treatment of diabetes?
pancreatic B cells
working beta cells, but defective ATP-sensitive K channels
what is the function of diazoxide on ATP-sensitive K channels within pancreatic B cells?
stimulates the ATP-sensitive K channels causing repolarisation and inhibits insulin secretion
what is MODY?
maturity-onset diabetes of the young
familial form of early-onset type 2 diabetes
what enzyme do mutations causing MODY affect?
glucokinase
what do MODY mutations do to the blood glucose threshold for insulin secretion?
increase the blood glucose threshold for insulin secretion
glucose sensing defect
why can MODYs be treated with sulphonylurea?
because they have working beta cells
what is the primary problem in type 2 diabetes?
reduced insulin sensitivity in tissues
what are the 3 amino acids that can be phosphorylated and why?
serine
threonine
tyrosine
because they have an OH group
what charge is introduce into the protein structure when serine, threonine or tyrosine are phosphorylated?
a large negative charge
what are the subunits of an insulin receptor?
2 extracellular alpha subunits
2 transmembrane beta subunits
what are the insulin-binding domains on the insulin receptor?
the 2 extracellular alpha subunits
what are the subunits of the insulin receptor linked by?
disulfide bonds
what does binding of insulin to the alpha subunits cause?
autophosphorylation of the beta subunits thus activating the catalytic activity of the receptor
glucose enters cells via what transporter?
GLUT 4
in which type of diabetes can ketoacidosis occur?
type 1 diabetes
where are ketone bodies formed?
liver mitochondria
what type of oxidation converts acetyl Co-A into ketone bodies?
beta-oxidation
when is acetyl coA converted to ketone bodies?
when there is no oxaolacetate to allow acetyl CoA to enter the TCA
why might oxaloacetate be unavailable for the TCA cycle?
during times of starving oxaloacetate is used for gluconeogenesis and is not generated through glycolysis
what is broken down into acetyl CoA?
fatty acids
why does ketoacidosis occur in type 1 diabetes?
when insulin isn’t injected, cells fail to receive enough glucose and therefore switch to fat breakdown.
fatty acids are broken down into acetyl CoA which can’t go through the TCA cycle so form ketone bodies
–> ketoacidosis
why is there no ketoacidosis normally in type 2 diabetes?
the high concentrations of insulin in inhibit lipase (the enzyme which breaks down triglycerides into glycerol and free fatty acids)
–> no excessive breakdown of fat resources
what does insulin do to the activity of hexokinase?
increases the activity of hexokinase
what does glucagon do to the activity of phosphofructokinase?
decreases the activity of phosphofructokinase
what are the 3 ketone bodies?
acetone
acetoacetic acid
beta-hydroxybutyric acid
compare the half lives of steroid hormones to tyrosine derivative hormones?
steroid hormones have a longer half life
how many transmembrane domains are there in a G-protein coupled receptor?
7 transmembrane domains
what are the 5 hormones secreted from the anterior pituitary?
- growth hormone (GH)
- luteninsing hormone/follicle stimulating hormone (LH/FSH)
- adrenocorticotrophic hormone (ACTH)
- thyroid stimulating hormone (TSH)
- prolactin (PRL)
what are the 2 hormones secreted from the posterior pituitary gland?
- ADH
- oxytocin
what does normal TSH usually indicate about thyroid function?
normal thyroid function
what does raised TSH usually indicate about thyroid function?
hypothyroid
what does low TSH usually indicate about thyroid function?
hyperthyroid
when might TSH not be a reliable marker of thyroid status?
when there is pituitary dysfunction eg secondary hypothyroidism (low TSH causing hypothyroid) or TSHoma (high TSH causing hyperthyroid)
what is released by the hypothalamus to stimulate the anterior pituitary to secrete ACTH?
CRH
corticotrophin-releasing hormone
what 2 hormones does cortisol have negative feedback upon?
CRH
(corticotrophin-releasing hormone)
ACTH
(adrenocorticotrophic hormone)
when is the best time to measure cortisol?
9am
why are cortisol levels highest in the morning?
prepares body for physiological demands of the day
what hormone released by the hypothalamus acts as a positive stimulatory hormone on the pituitary gland, causing it to release growth hormone?
-GHRH
growth hormone releasing hormone
growth hormone acts on the liver to produce what hormone?
insulin-like growth factor 1
IGF-1
what is a surrogate marker used to estimate GH activity?
IGF-1
insulin-like growth factor 1
when GH is at high concentrations, what will the surrogate marker IGF-1 be?
raised
when GH is at low concentrations, what will the surrogate marker IGF-1 be?
might be normal
other things cause the production of IGF-1
can IGF-1 measurement indicate GH hypersecretion or hyposecretion?
hypersecretion
when IGF-1 is high, GF is high; when IGF-1 is normal, GF might be normal or low- unable to tell
when should you measure testosterone?
9am
dopamine (produced by the hypothalamus) has what effect on the anterior pituitary gland in terms of prolactin secretion?
dopamine inhibits prolactin secretion
what autocrine/paracrine effect does prolactin have on target breast tissue?
positive feedback
what receptor mediates the effects or prolactin?
prolacin receptor (PRLR)
what effect does vasopressin have on blood vessels?
constriction
what effect does vasopressin have on the kidneys?
increases fluid reabsorption
what overall effect does vasopressin have on the blood pressure?
increases arterial pressure
what is cortisol deficiency caused by?
adrenal insufficiency due to
-primary adrenal failure
or
-pituitary disease (secondary hypoadrenalism)
in UK what is the most common cause of primary adrenal failure?
autoimmune (addison’s disease)
what is addison’s disease caused by?
primary adrenal failure caused by autoimmune destruction of the adrenal cortex
what is cushings syndrome?
cortisol excess for any reason
what is cushings disease?
cortisol excess due to pituitary problem
what are the 4 main causes of cortisol excess? (cushings syndrome)
- pituitary origin
- adrenal origin
- ectopic ACTH
- exogenous steoirds
if there is a hormone excess, should you do a suppression or stimulation test?
suppression test
if there is a hormone deficiency should you do a suppression or stimulation test?
stimulation test
how do you undertake dynamic testing of a deficiency in cortisol production?
stimulation test
-synacthen test
(synthetic ACTH)
how do you undertake dynamic testing of an excess in cortisol production?
suppression test
-using dexamethasone
are the 4 causes of cushings syndrome ATCH- dependent or independent?
- pituitary cause: ATCH- dependent
- adrenal cause: ATCH-independent
- ectopic cause: ATCH- dependent
- exogenous steroids:@ ATCH- independent
if there is a failure of cortisol suppression on low dose dexamethasone suppression testing, what does this indicate?
cushings syndrome
if there is a failure of cortisol suppression on low dose dexamethasone suppression testing, and the ATCH is low, what is the likely origin of cushings syndrome?
adrenal cause
if there is a failure of cortisol suppression on low dose dexamethasone suppression testing, and the ATCH is high, what is the likely origin of cushings syndrome?
pituitary, or ectopic aCTH
compare hormones released from posterior and anterior pituitary in terms of where they are synthesiseed?
hormones released from anterior pituitary are synthesised in the anterior pituitary gland
hormones released from the posterior pituitary are synthesised in the hypothalamus
what hormone produced from the hormone causes the release of LH/FSH within the pituitary?
GnRH
gonadotrophin releasing hormone
what does an insulin stress test measure?
the increase in growth hormone and cortisol
what do stress hormones do to the blood sugar?
increase
what is a synacthen test?
when you inject ACTH to measure cortisol response
stimulation test
is an insulin stress test a suppression or stimulation test?
stimulation test
what is a water deprivation test?
deprive patient of water for 8 hours and the measure concentration of urine
(it should have doubled by 2)
what hormone is a water deprivation test testing?
ADH
is a water deprivation test a stimulation or suppression test?
stimulation
what are the 5 physiological causes of raised prolactin?
breast feeding pregnancy stress sleep nipple stimulation
what are the 3 pathological causes of raised prolactin?
hypothyroidism (low DA)
stalk lesions
prolactinoma
what is the first line treatment for raised prolactin?
dopamine agonists
what do dopamine agonists do to prolactinomas?
make them shrink
is a glucose tolerance test for testing GH a stimulation or suppression test?
suppression test
compare the GH response in a patient with acromegaly to a normal response after a glucose tolerance test?
normal GH should decrease
acromegaly: GH will not be suppressed
what medications can be used in the treatment of acromegaly?
somatostatin analogues
(dopamine analogues,
GH antagonist)
what are the 3 short term side effects of somatostatin analogues?
flactulence
diarrhoea
abdo pain
what are the 2 long term side effects of somatostatin analogues?
gastritis
gallstones
how do you do a suppression test for cushings?
dexamethasone
exogenous steroid
compare normal response to exogenous dexamethasone to a cushings response?
normal: cortisol levels decrease
cushings: cortisol levels remain high
what is mineralocorticoid activity?
the retention of sodium in exchange for potassium or hydrogen ions
what is the main steroid with mineralocorticoid activity?
aldosterone
what organ makes renin?
kidneys
what is the function of renin?
converts angiotensinogen to angiotensin I
what happens to the rate of renin secretion if there is low blood pressure?
low blood pressure within the kidney causes increased rate of renin secretion
what happens to the concentration of the urine when there is increased ADH secretion?
increased concentration of urine
what happens to the concentration of the urine when there is decreased ADH secretion?
decreased concentration of urine (dilute)
does concentrated urine have a low or high osmolality?
high osmolality
does dilute urine have a low or high osmolality?
low osmolality
what are the 2 possible causes of low serum sodium? (ie in terms of water or sodium)
too much water
too little sodium
what are the 2 possible causes of high serum sodium? (ie in terms of water or sodium)
too much sodium
too little water
what are the 2 main reasons for too much water? (in terms of excretion and intake)
decreased excretion
increased intake
what condition causes increased intake of water which could cause decreased serum sodium?
compulsive water drinking
what does syndrome of inappropriate anti-diuresis (SIAD) do to the rate of water excretion?
decreases the rate of water excretion
what are the 2 main reasons for too little sodium? (in terms of excretion and intake)
decreased intake (rare) increased excretion
what 3 organs are the main areas within the body wear sodium is lost?
kidneys
gut
skin
what is addison’s disease?
adrenal insufficiency
why might there be increased sodium loss from the kidneys in addison’s disease?
insufficient aldosterone is produced and so not enough sodium can be retained
what are the 2 major reasons for sodium loss from the skin?
sweating
burns
what are the 2 main causes for too little water? (in terms of excretion and intake)
decreased water intake
increased water excretion
what is the name for disruption of water balance axis causing inappropriately increased water excretion?
diabetes insipidus
what goes wrong in diabetes insipidus?
- problem with ADH secretion (central diabetes insipidus)
- problem with ADH action on the kidneys (nephrogenic diabetes insipidus)
what is the main cause of too much sodium? (in terms of excretion or intake)
increased intake
what are the 3 main causes of increased sodium intake which can lead to increased serum sodium?
IV medications given as sodium salts
near-drowning in sea
high-salt infant feeds
a low BP which falls on standing points to the likelihood that what salt is low?
sodium
why might a patient with addison’s disease get symptoms of dizziness?
due to hypotension from too little water
why might a patient with addison’s disease have excess pigmentation?
the adrenal glands are insufficient and so the lack of aldosterone/cortisol negative feedback causes the ACTH levels to greatly increase.
ACTH is degraded by proteases causing a release of melanocyte stimulating hormone which causes pigmentation
when there is too much water due to inappropriate ADH secretion (SAID) what are the serum sodium levels and the volume status?
low serum sodium level
unremarkable volume status
what investigation is used to look for Addison’s disease?
serum cortisol
what does non-osmotic stimuli for ADH release do to the serum sodium?
decreases serum sodium
what is the problem (sodium or water) when there is hypovolaemia and hyponatraemia?
too little sodium
when is hypervolaemia most often seen?
oedema
what is pseudohyponatraemia?
when total sodium is low but serum osmolality is normal
what are trophic hormones?
hormones which act on other endocrine glands
what are non-trophic hormones?
hormones which act on target cells directly
what are the 4 trophic hormones produced by the anterior pituitary?
ACTH
TSH
FSH
LH
what are the 2 non-trophic hormones produced by the anterior pituitary?
GH
prolactin
what are the 3 main cell type within the anterior pituitary gland?
acidophils
basophils
chromophobes
what cells within the anterior pituitary gland produce growth hormone? and what type of cell is this?
somatotrophs
a type of acidophil
what cells within the anterior pituitary gland produce prolactin? and what type of cell is this?
mammotrophs
a type of acidophil
what cells within the anterior pituitary gland produce adrenocorticotrophic hormone? and what type of cell is this?
corticotrophs
a type of basophil
what cells within the anterior pituitary gland produce thyroid stimulating hormone? and what type of cell is this?
thyrotrophs
a type of basophil
what cells within the anterior pituitary gland produce FSH/LH? and what type of cell is this?
gonadotrophs
a type of basophil
what are the 2 main reasons for hyperfunction of the anterior pituitary gland?
adenoma
carcinoma
what are the 5 main reasons for hypofunction of the anterior pituitary gland?
- surgery/radiation
- sudden haemorrhage into gland
- ischaemic necrosis
- tumours extending into sella
- inflammatory conditions
what is the most common functional pituitary adenoma?
prolactinoma
what is panhypopituitarism?
pituitary hypofunction of all the anterior pituitary hormones
(not just individual ones)
what are craniopharyngiomas derived from?
remnants of rathke’s pouch
the pouch from which the anteiror pituitary was derived
craniopharyngiomas have a bimodal incidence, when are they prevalent?
- 5-15 years
- 60- 75 to years
what is the rare but serious complication of craniopharyngioma?
squamous cell carcinoma
esp following radiation
what are the 2 main causes for central diabetes insipidus?
ADH deficiency
trauma/surgery
what is the main cause of nephrogenic diabetes insipidus?
renal resistance to ADH
what type of hormones are produced from the adrenal cortex?
steroid hormones
what type of hormones are produced from the adrenal medulla?
catecholamine hormones
what are the 3 zones of the cortex?
zona glomerulosa
zona fasciculata
zona reticularis
what are the main hormones secreted by the zona glomerulosa of the adrenal cortex?
mineralocorticoids
eg aldosterone
what are the main hormones secreted by the zona fasciculata of the adrenal cortex?
glucocorticoids
eg cortisol
what are the main hormones secreted by the zona reticularis of the adrenal cortex?
androgens
what is the adrenal medulla innervated by?
pre-synaptic fibres from the sympathetic nervous system
what cells within the medulla secrete catecholamines?
chromaffin cells
what are the 3 main reasons for hyperfunction of the adrenal gland? (primary)
hyperplasia
adenoma
carcinoma
what are the 3 main causes of acute hypofunction of the adrenal gland? (primary)
- waterhouse-friderichsen
- rapid withdrawal of steroid treatment
- adrenal haemorrhage
what is the main cause of chronic hypofunction of adrenal gland? (primary)
addison’s disease
acquired adrenocortical hyperplasia can be ACTH driven or independent. Is diffuse hyperplasia ACTH driven or independent?
ACTH driven
acquired adrenocortical hyperplasia can be ACTH driven or independent. Is nodular hyperplasia usually ACTH driven or independent?
ACTH independent
what syndrome describes the effects of primary hyperaldosteronism?
conn’s syndrome
what are the 2 main causes of secondary hyperaldosteronism?
- increased renin
- decreased renal perfusion (ie hypovolaemia)
what are the 2 adrenal medullary tumours?
phaeochromocytoma
neuroblastoma
when are neuroblastomas diagnosed?
within 18 months usually
otherwise diagnosed in infancy
where do neuroblastomas arise?
adrenal medulla
sympathetic chain
what are phaeochromocytoma cells derived from?
chromaffin cells of the adrenal medulla
what hormones do phaeochromocytomas secrete?
carecholamines
what do phaeochromocytomas do to blood pressure?
cause it to drastically increase
what is the 10% phaeochromocytoma rule? (7)
10% are extra-adrenal 10% are bilateral 10% malignant 10% are not associated with hypertension 10% are associated with hyperglycaemia 10% in children 10% familial (more like 25% now)
are phaeochromocytomas part of MEN 1 or MEN 2?
MEN 2
what are the 7 main contents of the cavernous system?
- carotid artery
- cavernous sinus
- oculomotor nerve
- trochlear nerve
- opthalmic branch of trigeminal nerve
- maxillary branch of trigeminal nerve
- abducens nerve
what system regulates the aldosterone levels within the body?
the renin-angiotensin system
what doses of corticosteroids are use in the suppression of inflammation? (physiological, supraphysiological or subphysiological)
supraphysiological
what doses of corticosteroid are used in the suppression of immune system? (physiological, supraphysiological or subphysiological)
supraphysiological
what doses of corticosteroids are used in steroid replacement treatment? (physiological, supraphysiological or subphysiological)
physiological
what are the 4 main causes of primary adrenal insufficiency?
Addison’s (autoimmune)
congenital adrenal hyperplasia
adrenal malignancy
adrenal TB
compare Na and K levels in a patient with Addison’s disease to normal levels?
Na reduced
K increased
what stimulation test can be used in the diagnosis of primary adrenal insufficiency?
short synacthen test
ACTH IV/IM and measure plasma cortisol
when treating primary adrenal insufficiency what drugs are used as cortisol and aldosterone replacement?
hydrocortison to replace cortisol
fludrocortisone to replace aldosterone
why do you not need to give fludrocortisone to a patient with secondary adrenal insufficiency?
because aldosterone production will be preserved due to renin-angiotensin system
what is the most common cause of secondary adrenal insufficiency?
exogenous steroid use
compare the clinical features of secondary adrenal insufficiency to Addison’s?
similar except in secondary adrenal insufficiency the aldosterone production is intact, and the skin remains pale (no excessive ACTH)
what are the 3 main causes of ACTH dependent cushing’s syndrome?
pituitary adenoma (cushings disease)
ectopic ACTH
ectopic CRH
what are the 3 main causes of ACTH independent cushing’s syndrome?
adrenal adenoma
adrenal carcinoma
nodular hyperplasia
what are the 3 main screening tests used in cushings syndrome?
- overnight dexamethasone suppression test
- 24 hour urinary free-cortisol
- late night salivary cortisol
what is the definitive test for cushing’s syndrome?
low dose dexamethasone suppression test over 2 days
and repeat to confirm
why can prolonged high dose steroid therapy cause secondary adrenal deficiency?
chronic suppression of pituitary ACTH production and adrenal atrophy
what is the most common cause of cushing’s syndrome?
iatrogenic (due to high dose steroid therapy)
what is the most common cause of primary aldosteronism?
bilateral adrenal hyperplasia
what causes conn’s syndrome?
an adrenal adenoma
unilateral
what suppression test can be used for the diagnosis of primary aldosteronism?
saline suppression test
what is the treatment of a conn’s adenoma causing aldosteronism?
surgery
what is the treatment of bilateral adrenal hyperplasia?
use mineralocorticoid receptor antagonists eg spironolactone or eplerenone
what is the most common cause of congenital adrenal hyperplasia?
21a hydroxylase deficiency
an enzyme defect within the steroid pathway
what type of inheritence is 21a hydroxylase deficiency? (which leads to congenital adrenal hyperplasia)
autosomal recessive
what are the 2 variants of 21a hydroxylase deficiency?
classical
non-classical
compare classical and non-classical variants of 21a hydroxylase deficiency in terms of the extent of deficiency?
classical: complete deficiency
non-classical
how do you diagnose 21a hydroxylase deficiency?
basal or stimulated 17-OH progesterone level
in 17 hydroxylase deficiency, what is the only cortex hormone which can still be made?
aldosterone
in 21a hydroxylase deficiency, what is the only cortex hormone which can still be made?
testosterone (through DHEA)
what is the name for a extra-adrenal phaeochromocytoma?
paraganglioma
within the sympathetic chain
blocking sympathetic system is how some phaeochromocytomas are managed, which should be blocked first alpha or beta receptors?
alpha before beta
compare MEN 1 and MEN 2 in terms of type of genes affected?
MEN1: tumour suppressor gene is inactivated
MEN2: ongogene is activated into proto-oncogene
what type of inheritance is von hippel lindau syndrome?
autosomal dominant
what gene is mutated in von hippel lindau syndrome?
von hippel lindau tumour suppressor gene
what type of receptor does growth hormone signal via?
cytokine receptor
what type of receptor does calcium signal via?
g-protein coupled receptor
which facial nerve (trochlear or abducens) is involved in lateral gaze?
abducens
which facial nerve (trochlear or abducens) is involved in medial gaze?
trochlear
what receptor do TZDs work on?
PPARgama
what is the iodine uptake of acute thyroiditis on scan?
reduced/no uptake
compare macroprolacitinomas and microprolactinomas in terms of size?
macro over 1cm
micro under 1cm
what syndrome is usually present if there is metastatic disease to the pituitary gland/.
diabetes insipidus
why must you always give hydrocortisone before thyroxine in panhypopituitarism? (ie in a non-functioning tumour)
to prevent an addisonian crisis
what is the classic symptom triad of a phaeochromocytoma?
headaches
sweating
palpitations