hypoadrenal disorders Flashcards
describe the synthesis of adrenocortical steroids *
precurser is cholesterol
only small changes in the structure taht are casued by cytochrome P450 enzymes (dehydrogenase enzymes)
for aldosterone: cholesterol -> progesterone -> 11 deoxycorticosterone -> corticosterone -> aldosterone
for cortisol: cholesterol -> progesterone -> 17OH progesterone -> 11deoxycortisol -> cortisol
for sex steroids: cholesterol -> progesterone -> 17 OH progesterone -> sex steroids
testosterone is converted into oestradiol by aromatisation
effect of aldosterone *
promote retention of water and Na
excretion of K
effect of renin*
causes release of aldosterone in response to haemorrhage that means the kidney is underperfused
what are the causes of adrenal failiure *
adrenal glands destroyed (main cause) - TB/autimmune - autoimmune (Addison’s) is the main casue in the UK, bloof clot supplying the adrenal, metastasis, meningoccocal septicaemia
congenital adrenal hyperplasia - rare - enzymes missing/not working at full capacity
how does TB cause primary adrenal failure *
mycobacteria gets into the adrenal cortex and damages it
clinical features of adrenocortical failure *
mucus membrane/scar/skin pigmentation/darkening of hair - because of high POMC = high ACTH and MSH - stimulate melanocytes - if hypopit, wouldn’t get this because wouldnt make any ACTH
vitiligo - sign of autoimmune disease becasue if you have 1 autoimmune condition likely to have another, Ab destroy melanocytes so have hypopigmentation (addison’s)
postural hypotension - no aldosterone to increase the BP after a couple of mins of standing
hypoglycaemia - normally cortisol is involved in glucose release
loss of Na in urine, increased K in plasma - no aldosterone
exhaustion - no cholesterol
weight loss
anorexia
vomiting
muscle weakness
emaciation - abnormally thin/weak
diarrhoea
also have a loss of steroid hormones - loss of libido and decreased pubic hair (primary adrenocortical failure)
what do the adrenal glands look like when affexted by autoimmune?
atrophic - they have shrunk
medulla is normal - not affected by ACTH or autoimmune
appearance of adrenal gland affected by TB
granulomatous
cortex cant work - destroyed by the granulomas
appearance of the adrenals when affected by cancer
metastasis present
but cortex cant work
describe pro-opio-melanocortin *
synthesised in the pit
broken down to ACTH and MSH and endorphins and enkephalins and other peptides
(reason for pigmentation in Addison’s)
consequence of adrenocorticoid failure *
eventual death because of low Na - Addisonian crisis
how would you diagnose addison’s *
9am cortisol = low = 100 (normal 270-900)
ACTH - high
short synACTHen test
low Na, high K
look for anti-adrenal Ab - +ve in 60-70% of people with Addison’s
describe the 9am cortisol test *
got to be done in morning when cortisol should be high - because cortisol levels are diurnal
should be 270-900
in Addison’s it is 100
descrube the synacthen test *
give 250ug synacthen IM
ie synthetic ACTH - cortisol level should rise
measure cortisol level 30mins later
if cant make cortisol, there will be no response
normal >600, Addison’s = 150
diagnosis = Addison’s
describe congenital adrenal hyperplasia *
rare
commonest cause of this - 21-hydroxylase deficiency
can be complete/partial - ie not making the enzymes at alljust not making enough
cant make cortisol or aldosterone, so precursers are pushed into the sex steroid pathway = increase in sex steroids particulary testosterone
describe complete 21-hydroxylase deficiency *
pathway for aldosterone and cortisol blocked because no enzyme - so no aldosterone or cortisol
can survive < a few weeks - present within a week of birth with Addisonian crisis (hyponatraemia)
sex steroids and testosterone will be in excess because there will be a build up of precursers so they go down sex steroid pathway, also ACTH level high (in attempt to make cortisol) meaning even more precursers are made = more sex steroids and testosterone
what is the effect of raised sex steroids in congential adrenal hyperplasia *
virilisation in girls because exposed to too much testosterone in utero - ambiguous genitalia - need to karyotype child to see if XX or XY
precocious puberty in boys - presented with too much testosterone
boys can get testicular rest tissue - fibrous tissue instead of leidig and sertoli cells because of too uch ACTH
in women: acne, fascial hirsuitism, receding hair line, androgenic flush, variable pigmentation, small breasts, male escutcheon, muscular arms and legs, irregular periods
age of presentation of complete 21-hydroxylase deficiency |*
as a neonate with a salt losing Addisonian crisis - listless (floppy) baby, low BP (hypovolaemic shock - this indicates that the deficiency is 21 hydroxylase because if it was 11 - 11 deoxycorticosterone would have mineralocorticoid effects so there would be normal BP)
before birth - foetus gets steroids across the placenta
girls might have ambiuous genitalia
describe PARTIAL 21-hydroxylase deficiency *
cortisol and aldosterone are deficient
sex steroids and testosterone are in excess
they will present at any age that they survive until
adrenal glands are massive because of increased ACTH
describe 11-dehydroxylase deficiency *
deficiency in 11-dehydroxylase causes a build up of precursers including 11-deoxycorticosterone and 11 deoxycortisol
11-deoxycortisol has no bioactivity
cortisol and aldosterone are deficient
sex steroids, testosterone and 11-deoxycorticosterone are in excess
problems - virilisation, hypertension and low K
describe the action of 11-deoxycorticosterone and effect when it is in excess *
acts like aldosterone (is a mineralocorticoid)
therefore cause Na and water retention and K excretion
in excess casue hypertension and hypokalaemia
describe 17-hydroxylase deficiency *
rare
cortisol and sex steroids are deficient
11-deoxycorticosterone and aldosterone are in excess = hypertension, low K, sex steroid deficiency (more common in children) and hypoglycaemia (because glucocorticoid deficiency)
how do you investigate postural hypotension*
get ot to lie down, then stand up
take BP 2 mins after standing up - should be normal, if low they have postural hypotension
they would have to wait 2 mins because always going to be low initially
casues of postural hypotension
due to hypovolaemia - eg haemorrhage
or ANS problem not sensing change in BP so not causing vasoconstiction
