adrenal steroids Flashcards
mineralocorticoid deficiency signs
aldosterone
hyponatraemia
*hyperkalaemia
hypotension
metabolic acidosis (increased H+)
glucocorticoid deficiency (cortisol)
hyponatraemia
*hypoglycaemia
hypotension
likely combined glucocorticoid and mineralocorticoid deficiency
both
- hypoglycaemia
- hyperkalaemia
suggests primary adrenal problem
mechanism of glucocorticoid hyponatraemia
- unable to excrete water load (reduced glomerular filtration rate)
- loss of cortisol inhibition of antidiuretic hormone
(cortisol normally inhibits ADH release)
will retain more water and dilute you
mechanism of glucocorticoid hypoglycaemia
- reduced hepatic glucogenesis
mechanism of glucocorticoid hypotension
- loss of cortisol effects on vascular tone
poor organ perfusion e.g. kidneys
mechanism of mineralocorticoid hyponatramia
- urine Na+ loss with intravascular volume contraction and secondary ADH/vasopressin secretion
- potent vasoconstrictor
- more water retain from ADH not due to Na+ loss
mechanism of mineralocorticoid hyperkalamia
- reduced renal K+ excretion
due to lack of aldosterone
dehydration
loss of Na+ AND water
mechanism of mineralocorticoid metabolic acidosis
- reduced renal H+ excretion (increased H+)
due to lack of aldosterone
how is aldosterone made
lack of volume sensed at the juxta glomerular apparatus through Cl causing a release of renin
renin gets converted angiotensin 1
which then gets converted to angiotensin 2 via ACE
angiotensin 2 stimulates adrenal cortex to make aldosterone
(adrenal cortex also stimulates by ACTH and K+)
action of aldosterone
increase Na+ and H20 reabsorption
increase intravascular volume
causes of adrenal failure
primary = adrenal gland
secondary/tertiary
= pituitary/hypothalamus
what does a lack of cortisol stimulate
release of more cortisol-releasing factor (CRF) from the hypothalamus and therefore ACTH from the pituitary
how does a primary adrenal problem cause a tan
ACTH is a peptide product of POMC
POMC gets cleaved and produces melanocyte stimulating hormones MSH
therefore when you stimulate POMC to make more ATCH you also stimulate MSH
- increased levels of MSH in the bloodstream pigmentates your melanocytes
what regulates ACTH
regulated by cortisol
- is independent of mineralocorticoid axis
increased POMC and ACTH occurs with a lack of feeback inhibition e.g. decreased cortisol in primary adrenal failure
classically in primary adrenal insufficiency where is pigmentation seen?
more apparent in
- skin flexures
- nail beds
- mouth
- freckles
- old scars
how to tell if an obesity is pathological
- sudden change in appearance over time (not gradual)
pictures useful - growth pattern (children) pathological cause = shorter
glucocorticoid excess
in childhood = generalised obesity
causes profound growth failure
in adults = leads to truncal obesity
(obesity round the middle)
features of glucocorticoid excess
- moon face
- thinning skin
- glowing skin
- easily bruised
- androgen excess e.g. amenorrhoea / irregular periods and hairy
- myopathy
- diabetes
- hypertension
- oesteoporosis
cortisol binding and excess
cortisol binds to the mineralocorticoid receptor and the glucocortisol receptor with equal affinity
however cortisol is metabolised very quickly to cortisone and usually has no MC effect
IF kidney is overloaded with cortisol a mineralocorticoid effect can be observed
e.g. hypertension and hypokalaemia
most common cause of glucocorticoid excess at a young age
pituitary tumour producing ACTH = cushings disease
what do you get in you have partial loss of the glucocorticoid receptor
(note: receptor not hormone)
- brain isnt going to see as much cortisol therefore is going to release more ATCH from the pituitary
- ATCH makes adrenal glands bigger
- more cortisol released
- cortisol excess however will be seen as normal
- too much cortisol will bind to MC receptor
- mineralocorticoid excess –> hypokalaemia, hypertension
by products of cortisol is androgen
= glucocorticoid resistance
secondary mineralocorticoid effects
- alkalosis
- hypokalaemia
- hypertension
hyperandrogenism
fatigue/tiredness (cortisol insensitivity)
this is a result of cortisol excess binding to MC receptors
what do you get in you have a loss of function of the mineralocorticoid receptor
present as aldosterone deficiency
mineralocorticoid resistance
- high aldosterone and renin levels
- depleted extracellular fluid space = decreased ECF
- high serum K+ and low Na+ conc
what happens when the ACTH receptor has a loss of function e.g. mutation
small nonfunctioning area of the adrenal cortex
severe cortisol deficiency from birth
- hypotension
- low Na+
- hypoglycaemia
what does low cortisol levels lead to
high ACTH levels with secondary stimulation of the adrenal cortex, excess production of adrenal precursors (not cortisol but high levels of P4 and testosterone) and adrenal hyperplasia
low K+ and high BP are signs of what?
aldosterone/mineralocorticoid excess
