Adrenal Physiology and Disorders Flashcards
what are the 3 layers of the adrenal cortex from outer to inner?
zona glomerulosa
zona fasciculata
zona reticularis
what is secreted by each layer of the adrenal cortex?
zona glomerulosa = mineralocorticoids (e.g aldosterone)
zona fasciculata = glucocorticoids (e.g cortisol)
zona reticularis = adrenal androgens (e.g testosterone)
what is present within the adrenal medulla and what is secreted from here?
chromaffin cells
medullary veins
splanchnic veins
secretes catecholamines
describe the HPA axis,
hypothalamus releases CRH which stimulates pituitary to produce ACTH which stimulates adrenal cortex to produce cortisol
what can have an effect on the activity of the hypothalamus in the HPA axis?
illness
stress
time of day
negative feedback from cortisol levels
how are the kidneys involved in blood pressure?
kidney senses reduced BP > production of renin > converts angiotensinogen to angiotensin 1 > ACE converts angiotensin 1 to angiotensin 2 > angiotensin 2 acts on adrenals to produce aldosterone which acts back on the kidneys causing water and salt retention > increased blood pressure
how do corticosteroids work?
bind intracellular receptor in either the cytoplasm or the nucleus > receptor/ligand complex binds to DNA via phosphorylation > has effects on transcription
what are the 6 classes of steroid receptor?
glucocorticoid mineralocorticoid progestin oestrogen androgen vitamin D
how does cortisol affect the cardio/renal system?
increased CO, BP, renal blood flow and GFR
give 3 main principles of using cortisol in treatment?
suppress inflammation
suppress immune system
replacement therapy
how can cortisol be administered?
IV
intramuscular
orally
name 5 disease which cortisol can be used for?
asthma/anaphylaxis rheumatoid arthritis ulcerative colitis crohns malignancy
what are the functions of aldosterone?
sodium/potassium balance (K+ out, Na+ in)
BP regulation
Extracellular volume regulation
where are mineralocorticoid receptors present?
kidneys
salivary glands
gut
sweat glands
give an example of a classic presentation of addisons disease
unwell few months weight loss amenorrhoea vomiting/dairrhoea for past 48 hrs dark skin dehydrated hypotensive high K+, low Na+
what is the commonest cause of primary adrenal insufficiency?
addisons disease
what is addisons disease?
congenital autoimmune destruction of adrenal cortex
what are the features of addisons disease?
autoantibody positive in 70% anorexia weight loss fatigue/lethargy dizziness and low BP abdominal pain vomiting diarrhoea skin pigmentation associated with other autoimmune diseases (T1DM, autoimmune thyroid disease, pernicious anaemia)
name 2 other causes of primary adrenal insufficiency
congenital adrenal hyperplasia (CAH)
adrenal TB/malignancy
name 3 causes of secondary adrenal insufficiency?
all due to lack of excess ACTH stimulation
iatrogenic (excess steroid medication)
pituitary/hypothalamic disorders
tumours
what are the clinical features of secondary adrenal insufficiency?
similar to addisons apart from
- skin is pale due to no increased ACTH
- aldosterone production intact
how is secondary adrenal insufficiency managed?
hydrocortisone replacement
how is adrenal insufficiency diagnosed?
biochemistry short synacthen test ACTH levels (raised) renin/aldosterone levels adrenal antibodies
what does biochemistry show in adrenal insufficiency?
decreased Na+
increased K+
hypoglycaemia
describe the short synacthen test
measure plasma cortisol before and 30 mins after ACTH injection
normal = before >250nmol/L, after >550nmol/L
what causes skin pigmentation in adrenal insufficiency?
raised ACTH levels
describe renin/aldosterone levels in adrenal insufficiency
decreased aldosterone
increased renin
how is adrenal insufficiency managed?
hydrocortisone and cortisol replacement - IV first if unwell - 15-30mg daily - try to mimic diurinal rhythm fludrocortisone as aldosterone replacement education
what are the sick day rules for adrenal insufficiency?
double dose if at home and unwell
100mg IV followed by 50mg every 6 hours
cannot stop suddenly
what are the common presenting features of cushings?
central weight gain acne amenorrhoea hypertension severe osteoporosis proximal muscle weakness/myopathy easy bruising facial plethora striae proximal myopathy proximal muscle wasting
what are the 2 groups of causes of cushings?
ACTH dependant - pituitary adenoma - ectopic ACTH - ectopic CRH ACTH independent - adrenal adenoma - adrenal carcinoma - nodular hyperplasia
how is cushings disease diagnosed?
overnight dexamethasone suppression test (mainly)
24hr urinary free cortisol
late night salivary cortisol
what is the commonest cause of cushings syndrome?
iatrogenic - due to prolonged high dose therapy
- asthma, RA, IBD, transplant
- can be oral or inhaled steroids
how does steroid therapy affect the adrenal glands?
long term use can cause chronic suppression of pituitary ACTH production via negative feedback pituitary and adrenal atrophy
what are the implications of the effects of long term steroids on the adrenals?
unable to respond to stress
need extra dose when ill/surgical procedure
cannot stop steroids suddenly
gradual withdrawal of steroid therapy if taking over 4-6 weeks
name 2 endocrine causes of hypertension?
primary aldosteronism
congenital adrenal hyperplasia (CAH)
when would you suspect an endocrine cause of hypertension instead of an idiopathic case?
young
resistant hypertension
high clinical suspicion
what is primary aldosteronism?
autonomous production of aldosterone independent of its regulators (angiotensin 2 and potassium)
what are the 5 functions of aldosterone?
increases sympathetic outflow sodium retention cytokines and ROS synthesis increases cardiac collagen altered endothelial function - increased pressure response
what are the clinical features of primary aldosteronism?
significant hypertension
hypokalaemia
alkalosis
what are the 3 subtypes of primary aldosteronism?
bilateral adrenal hyperplasia (most common) adrenal adenoma (conns syndrome) rare causes (genetic, unilateral hyperplasia)
how is primary aldosteronism diagnosed?
ARR-aldosterone to renin ratio
- if raised, inveastigate further with saline suppression test
- if plasma aldosterone doesn’t suppress by 50% with 2L of saline = diagnosis of PA
how can you confirm the subtype of PA?
adrenal CT to demonstrate adenoma
can sometimes do adrenal vein sampling to confirm adenoma is true source of aldosterone excess
how is PA managed surgically?
unilateral laparoscopic adrenalectomy
- only if adrenal adenoma
- cures hypokalaemia and hypertension in most
how is PA managed pharmacologically?
if bilateral adrenal hyperplasia - use MR antagonists
- spironolactone
- eplerenone
what is congenital adrenal hyperplasia (CAH)?
rare group of autosomal recessive disorders with enzyme defects in the steroid production pathway
what is the most common form of CAH?
21 alpha hydroxylase deficiency
what are the 2 variants of 21 alpha hydroxylase deficiency?
classical - salt wasting - simple virilising non-classical - hyperandrogenaemia
how is 21 alpha hydroxylase deficiency diagnosed?
basal 17-OH progesterone
genetic mutation analysis
how does classical CAH present?
males - adrenal insufficiency - poor weight gain - biochemical pattern females - genital ambiguity
how does non-classical CAH present?
hirsute acne oligomenorrhoea precocious puberty infertility (or sub-fertility)
how is CAH managed in children?
quick recognition glucocorticoid replacement mineralocorticoid replacement in some surgical correction achieve max growth potential
how is CAH managed in adults?
control androgen excess
restore fertility
avoid steroid over-replacement
what is a phaeochromocytoma?
neuroendocrine tumour of the adrenal medulla originating from the chromaffin cells
what scan is used for phaeochromocytoma?
MRI
list 6 clues which could indicate a phaeochromocytoma?
labile hypertension postural hypotension paroxysmal sweating heachache pallor tachycardia can have none of the above
what is an extra-adrenal phaeochromocytoma known as?
paraganglioma
list 17 presenting symptoms of phaeochromocytoma
hypertension postural hypotension headache sweating palpitations breathlessness constipation anxiety fear weight loss flushing incidental finding on imaging pallor family history bradycardia tachycardia pyrexia
list 5 biochemical features of phaeochromocytoma?
hyperglycaemia low potassium high haematocrit mild hypercalcaemia lactic acidosis
how is phaeochromocytoma diagnosed?
catecholamines and metabolites in the urine can be first clue find source - MRI - MIBG - PET scan
how is a phaeochromocytoma managed?
full alpha and beta blockade (alpha and beta blockers)
fluids/blood replacement
careful anaesthetic assessment
surgery (laprascopy, excision, de-bulking)
chemotherapy if malignant
what is included in the follow up from phaeochromocytoma?
long term monitoring etc
genetic testing
family testing and investing
what 2 conditions is phaeochromocytoma associated with?
MEN2
Von-hippel- lindau syndrome
what are the metabolic effects of cortisol?
increased lipolysis
increased proteolysis
increased blood glucose
how does cortisol affect the immune response?
dampens the immune response
how does cortisol affect bone/connective tissue?
accelerates osteoporosis - reduced serum calcium, collagen formation and wound healing
how does cortisol affect the CNS?
mood lability, euphoria/psychosis, reduced libido
