adrenal gland Flashcards
what are the 3 zones of the adrenal cortex
glomerulosa
fasiculata
reticularis
what is made in the zona glomerulosa
mineralocorticoids
aldosterone
what is made in the zona fasiculata
glucocorticoids
cortisol
what is made in the zona reticularis
sex steroids
glucocortioids
what is the medulla of the adrenal gland innervated by
presynaptic fibres from sympathetic system (splanchnic nerves)
what are the neuroendocrine cells in the medulla of the adrenal gland called and what do they secrete
chromaffin cells
secrete catecholamines - adrenaline and noradrenaline
how is the release of cortisol and androgen from the adrenal gland controlled
HPA axis
how is the release of aldosterone from the adrenal gland regulated
RAAS and plasma potassium
activated in response to fall in BP
where are mineralocorticoid receptors for aldosterone found
kidneys
salivary glands
sweat glands
gut
what are the effects of aldosterone via mineralocorticoid receptors
sodium reabsorption
K+/H+ excretion
–> BP regulation, ECFV regulation and sodium/potassium balance
what is the cause of CAH
deficiency of enzymes required for steroid biosynthesis
what is the enzyme most commonly deficient in CAH
alpha-21-hydroxylase
what is the inheritance pattern of CAH
autosomal recessive
how does a lack of alpha-21-hydroxylase cause cortical hyperplasia
lack of cortisol causes release of ACTH from hypothalamus causing hyperplasia of the adrenal gland
what are the 2 main presentations of CAH
classical - simple virilising/salt wasting
non-classical - hyperandrogenaemia
how does classical CAH present
salt wasting crisis at 2-3 weeks age
female genital ambiguity
poor weight gain
high potassium low sodium
how does non-classical CAH present
hirsute acne oligomenorrhoea precocious puberty masculinisation infertility/subfertility
does non-classical or classical present earlier
classical
how can CAH be diagnosed
basal or stimulated 17-OH progesterone
genetic mutation analysis
synacthen
what is the treatment for CAH
replace glucocorticoid
replace aldosterone (in some)
surgical correction
in older - correct androgen excess
true/false
adrenocortical tumours are more common in females
false - equal men and women
what are the 2 main types of adrenocortical tumours
adrenocortical adenoma
adrenocortical carcinoma
how would you describe an adrenocortical adenoma
well circumscribed encapsulated lesion buried within gland
what colour are adrenocortical adenomas
yellow/yellow-brown surface (lipid)
what size are adrenocortical adenomas?
do they cause a mass lesion?
usually small 2-3cm
no
do adrenocortical adenomas usually occur alone or multiple
solitary
adrenocortical adenomas are composed of cells resembling —-
adrenocortical cells
what may been seen in adrenocortical adenomas
spironolactone bodies
what are the nuclei like in adrenocortical adenomas
small
are mitoses rare or common in adrenocortical adenomas
rare
are adrenocortical adenomas usually functional or non-functional
can be functional but usually not
Can cause Conn’s syndrome
is the adjacent and contralateral tissue in adrenocortical adenomas atrophic
no - ACTH not suppressed so adjacent and contralateral tissue not atrophic
are adrenocortical carcinomas functional
more likely to be
although adrenocortical carcinomas can resemble adrenocortical adenomas, what are some features suggestive of a carcinoma
large size haemorrhage and necrosis frequent, atypical mitoses lack of clear cells capsular or vascular invasion
what is the 5 year survival rate of adrenocortical carcinomas
20-30%
50% dead in 2 years
what is an example of a functional adrenocortical carcinoma
androgen secreting tumour
how would an androgen secreting adrenocortical carcinoma be diagnosed
MRI of adrenals and ovaries
what would happen with an androgen secreting adrenocortical carcinoma
rapid onset symptoms
virilisation
high levels testosterone
where would an adrenocortical carcinoma spread locally
retroperitoneum
kidney
where would mets of an adrenocortical carcinoma tend to go/spread
haem spread
liver, lung, bone
where else might an adrenocortical carcinoma spread
peritoneum
pleura
what is primary hyperaldosteronism
autonomous production of aldosterone independent of its regulation
primary hyperaldosteronism is the commonest secondary cause of what
hypertension
what is the most common cause of primary hyperaldosteronism
adrenal adenoma (Conn’s syndrome)
what is the second commonest cause of primary hyperaldosteronism
bilateral adrenal hyperplasia
what is a genetic mutation that can cause Conn’s syndrome
mutation in the KCNJ5 channel
what is the KCNJ5 channel
rectifying selective channel that maintains membrane hyperpolarisation - mutations lead to loss of selectivity and Na+ entry and depolarisation
give 2 other rare causes of primary hyperaldosteronism
adrenal carcinoma
unilateral hyperplasia
what is the main s/s of primary hyperaldosteronism
significant hypertension
what happens to potassium levels in primary hyperaldosteronism
hypokalaemia
do you get acidosis or alkalosis with primary hyperaldosteronism
alkalosis
what causes hypertension in primary hyperaldosteronism
Na reabsorption - water retention
what would the renin levels be like in primary hyperaldosteronism
decreased renin
what are the 2 stages in diagnosing primary hyperaldosteronism
confirm aldosterone excess
confirm subtype
how do you confirm aldosterone excess in primary hyperaldosteronism
measure of aldosterone to renin plasma ratio
if raised, further investigate with a saline suppression test
what would happen in a saline suppression test with primary hyperaldosteronism
failure of plasma aldosterone to suppress by >50% with 2L normal saline - primary hyperaldosteronism
how do you confirm the subtype of primary hyperaldosteronism
adrenal CT/adrenal vein sampling for adenoma
what is the treatment of Conn’s
unilateral laparoscopic adrenalectomy
what is the treatment of bilateral adrenal hyperplasia
MR antagonists
give 2 examples of MR antagonists
spironolactone
eplerenone
what can cause secondary hyperaldosteronism
high renin from decreased renal perfusion
what are some causes of acute primary adrenocortical hypofunction
Waterhouse-friderichsen (bilateral adrenal cortex haemorrhage) - commonly after infection
rapid withdrawal of steroid treatment
adrenal crisis in patient with chronic adrenocortical insufficiency due to stress
what is the most common cause of primary adrenal insufficiency
addisons
what is a cause of secondary adrenocortical hypofunction
lack of ACTH stimulation
- hypopituitarism
- suppression of adrenal cortex (exogenous steroids)
what is addisons disease
autoimmune destruction of the adrenal cortex leading to glucocorticoid and mineralocorticoid deficiency
what percentage of people with addisons are antibody positive
70%
what are some s/s of addisons
weakness fatigue anorexia N+V weight loss craving salty food tearful/depression vitiligo diarrhoea constipation skin pigmentation dizzy/faint low BP abdominal pain myalgia arthralgia postural hypotension
what causes the skin pigmentation in addisons
ACTH cross reacts with melanin receptors
what would the Na and K levels be like in addisons
low Na
high K
would someone with addisons by hypo or hypertensive
hypotensive
would someone with addisons by hypo or hyper glycaemia
hypogylcaemia
what other biochemistry might be seen in someone with addisons
uraemia
increased calcium
eosinophilia
anaemia
how is addisons diagnosed
biochemistry
short synacthen test
adrenal autoantibodies
describe a short synacthen test and what results would be normal as baseline cortisol and after the test
measure plasma cortisol before and 30 mins after IV/IM ACTH injection
normal:
cortisol baseline > 250 nmol/L
cortisol after ACTH > 550nmol/L
what would the levels of ACTH and renin be like in addisons
raised
what is the treatment for addisons
hydrocortisone + fludrocortisone
how should dosage be changed in a person with addisons if they are ill/injured/stressed
double dose
should you wait until a diagnosis before starting treatment?
no - start treatment before disgnosis
what is the treatment for an adrenal crisis
hydrocortisone 100mg IV
IV fluid bolus
monitor blood glucose - risk of hypo
if high K - calcium gluconate
would someone with secondary adrenal insufficiency have tinted skin
no - no increased ACTH
what are the 2 main tumours of the adrenal medulla
neuroblastoma
phaeochromocytoma
when are neuroblastomas usually diagnosed
around 18 months
40% of neuroblastomas arise in the adrenal medulla - where do the rest arise?
along sympathetic chain
how do the cells in a neuroblastoma appear
primitive but can show maturation/differentiation towards ganglion cells
what 2 genetic features predict a poor outcome of neuroblastoma
amplification of n-myc
expression of telomerase
what is a phaechromocytoma
neoplasm derived from chromaffin cells of adrenal medulla that secretes catecholamines
where do phaeochromocytoma mets go
skeletal, regional lymph nodes, liver, lung
what is the appearance of a phaeochromocytoma
necrotic tumour mass and may see adrenal remnants on surface
yellow/red-brown
necrotic
haemorrhagic
why will potassium chromate turn tumour dark brown
oxidation of catecholamines in tumour cells
tumour cells in phaeochromocytoma form nests what are these called
zellballen
what are the 6 10% rules of phaeochromocytoma
10% extra adrenal 10% bilateral 10% malignant 10% not assoc. hypertension 10% familial 10% assoc. hyperglycaemia
where do extra-adrenal phaeochromocytoma occur
along sympathetic chain
when phaeochromocytomas occur extra adrenally what are they called
paraganglioma
where exactly do paragangliomas occur
organs of Zuckerkandl (aortic bifurcation)
carotid body
what is the only definitive evidence of malignancy with phaeochromocytoma
mets
if a phaeochromocytoma is familial, is it more or less likely to occur in someone who is younger and is it more or less likely to be bilateral
more likely to be younger and bilateral
phaeochromocytoma is more often malignant if assoc. with what germline mutation
germline mutation of beta subunit of succinate dehydrogenase
what is the classic presenting triad of phaeochromocytoma
hypertension (50% paroxysmal)/tachycardia/palpitations
headache
sweating
what other s/s may be seen in phaeochromocytoma
palpitations breathlessness constipation anxiety weight loss flushing pallor pyrexia
what are some complications of phaeochromocytoma
paralytic ileus of bowel LV failure myocardial necrosis stroke shock
what would K and Ca levels look like in phaeochromocytoma
low K
mild hypercalcaemia
what would to the WCC in phaeochromocytoma
increased
what would happen to the haematocrit in phaeochromocytoma
high
would people with phaeochromocytoma be more likely to be acidotic or alkalotic
lactic acidosis
who should be investigated for phaeochromocytoma
family members with syndromes resistant HT HT < 50 classical symptoms HT with hyperglycaemia
what is an investigation for phaeochromocytoma
urine analysis of vanillymandelic acid (VMA) - may be false +ves
what are the 2 stages in diagnosing phaechromocytoma
confirm catecholamine excess
identify source of catecholamine excess
how can you confirm catecholamine excess
urine - 2 x 24 hr catecholamines or metanephrines
plasma - ideally at time of symptoms
how can you confirm the source of catecolamines
MRI/CT
MIBG scan
PET scan
what is an MIBG scan
meta-iodobenzylguanidine scan - looks for extra adrenal tumours
what is the treatment of phaeochromocytoma
full alpha and beta blockade
laparoscopic total excision if possible/tumour debulking
chemo if malignant - radio labelled MIBG
what comes first alpha or beta blockade in phaeochromocytoma
alpha before beta
what is an example of an alpha blocker
phenoxybenzamine
what is an example of a beta blocker used in phaeochromocytoma
propranolol, atenolol, metoprolol
if someone has borderline catecholamine excess what test can be done
clonidine suppression test
give 5 syndromes where phaeochromocytoma may be seen
MEN2A/2B VHL syndrome succinate dehydrogenase mutations neurofibromatosis tuberose sclerosis
what else might cause catecholamines to be raised
heart failure
why might someone with phaeochromocytoma have normal catecholamine levels
episodic secretion
what is cushings syndrome
excess cortisol
what is cushings disease
cushings syndrome caused by pituitary adenoma
are men or women more likely to get cushings
women
what is the most common cause of cushings
pituitary adenoma
what is a pituitary adenoma and how does it cause cushings
tumour arising from corticotroph cells of anterior pituitary - secretes ACTH
is a pituitary adenoma an ACTH dependent or indepentent cause of cushings
ACTH dependent
is adrenal adenoma/carcinoma an ACTH dependent or indepentent cause of cushings
ACTH independent
is ectopic CRH from medullary thyroid cancer/prostate cancer an ACTH dependent or indepentent cause of cushings
ACTH dependent
is an adrenal nodular hyperplasia an ACTH dependent or indepentent cause of cushings
ACTH independent
is ectopic ACTH from a paraneoplastic syndrome an ACTH dependent or indepentent cause of cushings
ACTH dependent
what paraneoplastic syndrome causes ectopic ACTH release
small cell lung carcinoma
what 3 things can cause pseudocushings
alcohol
depression
prolonged steroid medication
what 2 genetic syndromes can cause cushings
Carney complex
Mccune Albright
both ACTH independent
what is the first step in diagnosing cushings
confirm raised plasma cortisol - overnight dexamethasone suppression test
describe the overnight dexamethasone suppression test
1mg PO at midnight and measure serum cortisol at 8am
normal: cortisol suppressed to < 50
cushings: no suppression
what is a normal level for 24hr urinary free cortisol
< 250
what is a normal value for cortisol/creatinine ratio
< 25
what is another easy test to do to measure serum cortisol
late night salivary cortisol
describe a 48hr low dose dexamethasone suppression test and the findings
0.5mg/6hr PO for 2 days
normal: cortisol suppressed to < 50 (6hrs after last dose)
cushings syndrome: no suppression
how would you find out if the cause of cushings was pituitary after discovering that the person does have cushings using 48hr low dose dexamethasone suppression test
48 hour high dose dexamethasone suppression test
- 2mg/6hr
pituitary cause - suppression
other cause - no/part suppression
what are 2 other localising tests
plasma ACTH
CRH test
if plasma ACTH is undetectable what is likely
adrenal tumour
if you suspected an adrenal tumour what tests would you carry out
CT adrenals
or adrenal vein sampling or adrenal scintigraphy (if no mass found)
would plasma ACTH be higher in ectopic ACTH or a pituitary adenoma
ectopic ACTH
describe a CRH test
100 ug CRH IV and measure cortisol at 120 mins
what would the results of a CRH test show if cushings was caused by pituitary disease
cortisol rises
what would you do if you suspected pituitary disease
MRI pituitary
in ectopic ACTH production what would the CRH test show
cortisol doesnt rise
if you suspected ectopic production of ACTH what tests would you carry out
IV CT contrast of chest,abdo,pelvis
+/- MRI neck, thorax, abdomen
pituitary cause LDDT
no suppression
pituitary cause ACTH
< 300
pituitary cause HDDT
suppression
pituitary cause CRH
cortisol rises
adrenal cause LDDT
no suppression
adrenal cause ACTH
<1
adrenal cause HDDT
no suppression
ectopic LDDT
no suppression
ectopic ACTH
> 300
ectopic HDDT
no suppression
ectopic CRH
cortisol doesnt rise
