Adrenal Disorders Flashcards
what does the adrenal cortex produce
glucocorticoids (cortisol)
mineralocorticoids (aldosterone)
androgens
what regulates cortisol/ androgen secretion
pituitary ACTH (which is regulated by hormones made in the hypothalamus)
what controls aldosterone secretion
renin-angiotensin system
and
plasma K+
what is the role of aldosterone (mineralocorticoid)
regulates blood pressure and electrolyte excretion
what long term treatment does adrenal insufficiency need
lifelong replacement of cortisol and aldosterone
what can cause cortisol excess
iatrogenic
due to disorders of pituitary (ACTH dependent)
or adrenal gland (non ACTH dependent)
what can cause aldosterone excess
bilateral adrenal hyperplasia
adrenal adenoma
how is adrenal adenoma treated
surgically
what does aldosterone excess cause
hypertension
how much does a healthy adrenal gland weigh
4 grams in adults
what does the medulla of the adrenal gland produce
catecholamines- adrenalin and noradrenaline
what is corticosterone
a glucocorticoid
what are the zones of the adrenal gland and what do they produce
(from capsule to medulla)
zona glomerulosa (mineralocorticoids)
zona fasciculata (glucocorticoids)
zona reticularis (adrenal androgens)
what is released by the hypothalamus which stimulates the anterior pituitary to produce
corticotropin releasing hormone
what does the hypothalamus release corticotropin releasing hormone in response to
illness, stress, time of day
what does ACTH do
acts on adrenal cortex to release cortisol
what is the HPA axis
hypothalamus - (anterior) pituitary - adrenal cortex
what does cortisol have a negative feedback effect on
both the hypothalamus and the anterior pituitary
what activates the renin-angiotensin system
decreased blood pressure
describe the pathway of the renin angiotensin system (its not that bad chill)
blood pressure falls - kidney produces renin - renin acts on angiotensinogen... - ...forms angiotensin I - angiotensin-converting enzyme turns it into... - angiotensin II which has two actions... - 1. stimulates adrenal gland to secrete aldosterone which.... - causes the kidneys to retain salt (indirectly increases BP) - 2. causes direction vasoconstriction (directly increased BP) = increased blood pressure
what do corticosteroids do
bind to intracellular receptors
receptor ligand complex binds DNA to alter transcription
what are mineralocorticoids and glucocorticoids
corticosteroids
what are the 6 different types of steroid receptors
glucocorticoid mineralocorticoid progestin oestrogen androgen vitamin D
what are the CNS effects of cortisol
mood lability
euphoria/psychosis
decreased libido
what are the effects of cortisol on bone/ connective tissue
accelerates osteoporosis
decreased: serum calcium, collagen formation, wound healing
what are the immunological actions of cortisol
decreased:
- capillary dilation, permeability
- leucocyte migration
- macrophage activity
- inflammatory cytokine production
(reduces immune response)
what are the metabolic effects of cortisol
increased blood sugar
increased lipolysis, central redistribution of lipids
increased proteolysis
what are the circulatory/ renal effects of cortisol
increased cardiac output
increased blood pressure
increased renal blood flow and GFR
what are the clinical uses of corticosteroids
suppress inflammation
suppress immune system (both supraphysiological levels)
replacement treatment (physiological levels)
what diseases are corticosteroids used to treat
allergic diseases: asthma/ anaphylaxis
inflammatory disease: RA, UC, crohns
malignant disease
how can you administer corticosteroids
IV, IM orally
where are mineralocorticoid receptors
kidneys, salivary glands, gut, sweat glands
how does aldosterone affect mineral balance
causes excretion of K+/H+
causes reabsorption of sodium
what is this: 21 year old female ‘unwell’ for few months Weight loss Amenorrhoea Acutely unwell over past 48 hours with vomiting and diarrhoea On examination: Dark skin Dehydrated Hypotensive decreased Na increased K
addisons disease going into addisonian crisis
what should you worry about with hyperkalaemia and hyponatraemia
ADDISONS - IF YOU SUSPECT THIS TREAT IT IMMEDIATELY
what can cause primary adrenal insufficiency
addisons disease
congential adrenal hyperplasia (CAH)
adrenal TB, HIV, malignancy
what are the causes of secondary adrenal insufficiency
lack of ATCH stimulation:
iatrogenic (excess exogenous steroid)
pituitary/ hypothalamic disorder
what is CAH
congenital adrenal hyperplasia- block in production of adrenal corticosteroid, present in neonates or early childhood
milder forms can present in adulthood
what is addisons disease
autoimmune condition causing destruction of the adrenal cortex resulting in adrenal insufficiency
what is the commonest cause of primary adrenal insuffiency
addisons disease
does addisons present early or late in the disease
more than 90% of adrenal cortex destroyed before symptoms start
what other conditions are associated with addisons
autoimmune conditions:
- T1DM
- autoimmune thyroid disease
- pernicious anaemia
what are the clinical features of addisons disease
anorexia, weight loss fatigue. lethargy dizziness and low BP abdo pain, vomiting, diarrhoea increased skin pigmentation
what tests can be done to diagnose adrenal insufficiency
biochem: decreased Na, increased k, hypoglycaemia
short synacthen test: see if cortisol is produced
ACTH levels: increased (causes skin pigementation)
renin/aldosterone levels: increased renin, decreased aldosterone (loss in water and sodium)
adrenal autoantibodies
imaging
what antibodies can be used to investigate pimary adrenal insufficiency
17-OH-progesterone (infants and some childre/adults)
21-OH antibody (all > 6 months old)
what happens to CRH and ACTH if cortisol not produced
increase as loose negative feedback
how do you manage adrenal insufficiency
do not wait for diagnosis
hydrocortisone as cortisol replacement (if unwell IV) try to mimic diurnal rhythm to avoid sleep disturbance
fludrocortisone as aldosterone replacement (monitor BP and K)
fluids (saline as sodium deficiency)
need to wear identification
what are the sick day rules for adrenal insufficiency
double the dose of oral hydro-cortisone at time of inter current illness
if vomit it up admit to hospital (to get IV)
what is the treatment for an acute adrenal illness
rapid IV saline
hydrocortisone IV
what hormones are lacking in secondary adrenal insufficiency
either CRH or ACTH
what is the treatment for pituitary/ hypothalamic disease tumours
surgery/ radiotherapy
do you need to replace mineralocorticoid in secondary adrenal insufficiency (fludrocortisone)
no
what are the clinical features of secondary adrenal insufficiency
lack of CRH or ACTH
similar to addisons but- skin pale (no increased ATCH), aldosterone production intake
how do you treat secondary adrenal insufficiency
hydrocortisone replacement
how do exogenous steroids cause secondary adrenal insufficiency
have negative affect on ACTH and CRH
what are the normal levels for cortisol after a synthacthen test
baseline >250 nmol/L
post ACTH > 550 nmol/L
if below this think adrenal insufficiency
what is this: 17 year old female 3 year history of: Central weight gain Acne Amenorrhoea Hypertension Severe osteoporosis Proximal muscle weakness (myopathy)
cushings
what is cushings syndrome
prolonged exposure to excess cortisol - has high mortality
who is cushings common in
women, ages 20-40
what are the clinical features of cortisol excess
easy bruising facial plethora striae proximal myopathy and muscle wasting moon face red (plethoric) cheeks centripetal obesity intrascapular fat pad
what are the ACT dependent causes of cushings
(all driven by high levels of ACTH)
- pituitary adenoma
- ectopic ACTH (carcinoid/ carcinoma)
- ectopic CRH
(in order of most to least common)
what are the ACTH independent causes of cushings
adrenal adenoma
adrenal carcinoma
nodular hyperplasia
or exogenous glucocorticoids
ACTH dependent cushings originated from a pathology affecting where
the pituitary gland (or ectopic)- causes too much ACTH production
ACTH independent cushings originated from a pathology affecting where
adrenal glands (or exogenous steriods)- causes too much cortisol production
how do establish the cause of cushings
overnight dexamthasone suppression test (giving exogenous steroid should suppress production of cortisol)
24 hours urinary free cortisol
late night salivary cortisol
what is the commonest cause or cortisol excess
iatrogenic - due to prolonged high dose steroid therapy causing chronic suppression of pituitary ACTH and adrenal atrophy
‘Cushing’s syndrome is caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids’
cortisol is a glucocorticoid
what does long term steroid treatment do to ACTH production
suppresses it (negative feedback)
what does long term steroid treatment do to the adrenal glands
causes atrophy of adrenal cortex
what are the implications of adrenal suppression (e.g. due to long term steroid treatment)
unable to respond to stress (illness surgery)
need extra doses of steroid when ill/ surgical procedure
cannot stop steroids suddenly
how long should long term steroid therapy be withdrawn for
> 4-6 weeks
what is this: 34 year old male 1 year history of hypertension No other past medical history No regular medications On examination: BP 168/98 mm Hg Renal function normal but plasma potassium low
endocrine cause of hypertension:
-hypertension + hypokalaemia = primary aldosteronism
what are the endocrine causes of hypertension
cushings - too much glucocorticoid
pheochromocytoma- secretes high amounts of catecholamines
acromegaly- too much growth hormone
what is a pheochromocytoma
neuroendocrine tumour of the medulla of the adrenal glands
what are the biochemical signs of conns
hypokalaemia
what causes conns
an adrenal adenoma
what is primary aldosteronism
autonomous production of aldosterone independent of its regulators (angiotensin II/ potassium)
what can cause primary aldosteronism
a benign growth in adrenal gland- (adrenal adenoma)= conns syndrome
bilateral adrenal hyperplasia
rarer: adrenal cortical carcinoma, genetic mutations, unilateral hyperplasia
what is the action of aldosterone
blocks the action of sprionolactone
what are the cardiovascular effects of aldosterone
increased cardiac collagen
increased BP
left ventricular hypertrophy
atheroma
what are the CNS effects of aldosterone
increases sympathetic outflow
what are the cellular effects of aldosterone
increases cytokine and reactive oxygen species synthesis
alters endothelial function (increased pressure response)
what is the commonest cause of secondary hypertension
primary aldosteronism
what are the clinical features of primary aldosteronism
hypertension
hypokalaemia
alkalosis
mutations in what drives conns adenomas and hereditary hypertension
potassium channel mutations
how do you diagnose primary aldosteronism
step 1- confirm aldosterone excess: measure plasma aldosterone and renin ratio, if raised do saline suppression test. failure of plasma aldosterone to suppress by >50% with 2 litres of saline confirms PA
step 2 - Confirm cause: adrenal CT to demonstrate adenoma, sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess
what is the treatment for conns
unliateral laparoscopic adrenalectomy
what is the treatment for bilateral adrenal hyperplasia
MR antagonists (spironolactone, eplerenone)
what is congenital adrenal hyperplasia
group of conditions associated with enzyme defects in the steroid pathway
what is the most common enzyme deficiency causes CAH
21alpha hydroxylase deficiency
what inheritance pattern does 21alpha hydroylase deficiency follow
autosomal recessive inheritance
what are the variants of 21alpha hydroxylase deficiency
classical: salt wasting, simple virilising
non classical: hyperadrongenaemia
how do you diagnose CAH
basal (or stimulates) 17-OH progesterone (in excess as ant be converted into cortisol)
can stimulate 17-OH progesterone with synacthen (measure that it rather than cortisol)
what is the presentation of congential adrenal hyperplasia
males:
- adrenal insufficiency (2-3 weeks)
- poor weight gain
- biochemical pattern (similar to addisons)
females:
-genital ambiguity
non classical:
- hirsute
- acne
- oligomenorrhoea
- precocious puberty
- infertility or sub fertility
what is the paediatric treatment for congential adrenal hyperplasia
glucocorticoid replacement
mineralocorticoid replacement (in some)
surgical correction
achieve maximal growth potential
what is the treatment for CAH in adults
give mineralocorticoids and glucocorticoids (cortisol and aldosterone) to suppress androgen production (gives negative feedback to stop ACTH being produced)
what other forms does adrenaline as it is being made
dopamine and noradrenaline
what is adrenaline synthesised from
tyrosine
why might tumours of the adrenal medulla secrete dopamine
as unable to convert it to noradrenaline or adrenaline
what is this: 28y/o female 1998 - dyspnoea, palpitations echocardiogram = poor LV function ? viral cardiomyopathy
1999 - pregnancy
deterioration in cardiac function
BP - 154/110 at 26 weeks
noradrenaline = 1200nmol/24 hr (900)
adrenaline = 150 nmol/24 hr (200)
dopamine = 31,140 nmol/24hr (2800)
noradrenaline = 4.9nmol/l (<4)
adrenaline = 0.6nmol/l (<1)
CT shows extra adrenal mass
paraganglioma
are the majority of pheochromocytomas benign or malignant
benign
what are the symptoms of a pheochromocytoma
labile hypertension
postural hypotension
paroxysmal sweating, headache, pallor, tachycardia, pyrexia
Palpitations Breathlessness Constipation Anxiety/Fear Weight loss Flushing – uncommon Incidental finding on imaging Family tracing
what is the difference between a pheochromocytoma and a paraganglioma
pheochromocytoma are in the adrenal medulla
paragangliomas are extra adrenal
what is the 10% percent tumour
a pheochromocytoma
when do pheochromocytomas pose greater risks
in surgery and pregnancy
what are the signs of complications of a pheochromocytoma
LVF, myocardial necrosis, stroke, shock, paralytic ileus of bowel
what are the biochemical abnormalities of pheochromocytomas
Hyperglycaemia – adrenaline secreting tumours
May have low potassium level
High haematocrit – i.e. raised Hb concentration
Mild hypercalcaemia
Lactic acidosis – in absence of shock
how is the pheochromocytoms the 10% tumour
10% malignant 10% extra-adrenal [probably 20-30%] 10% bilateral 10% associated with hyperglycaemia 10% in children 10% familial (but probably 25%)
when should you think pheochromocytomas
Family members with syndromes Resistant hypertension The young [<50] with hypertension Classical symptoms Consider with hypertension and hyperglycaemia
how do you diagnose pheochromocytomas
confirm catecholamine excess: urine, plasma
identify source: MRI of abdomen/ whole body
MIBG scan
PET scan
how do you treat pheochromocytoma
full alpha and beta blockade (A before B as other way around will cause profuse vasoconstriction)
alpha- phenoxybenzamin
beta- propranolol, atenolol, metoprolol
-fluid and/or blood replacement (as blockade will cause vasodilatation)
surgery
chemo if malignant
long term follow up
genetic testing
what syndromes are associated with pheochromocytomas
MEN2, von-hippel-lindau syndrome, SDH B (B for bad), SDH D (D for get it from Dad)
what happens to catecholamines in heart failure
are raised (as stress put on the heart)
what ‘pheochromocytoma’ or adrenal tumours are less efficient at producing catecholamines
malignant or extra adrenal tumours
