hypoadrenal disorders

Question 1

describe the synthesis of adrenocortical steroids *

Answer 1

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

Question 2

effect of aldosterone *

Answer 2

promote retention of water and Na

excretion of K

Question 3

effect of renin*

Answer 3

causes release of aldosterone in response to haemorrhage that means the kidney is underperfused

Question 4

what are the causes of adrenal failiure *

Answer 4

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

Question 5

how does TB cause primary adrenal failure *

Answer 5

mycobacteria gets into the adrenal cortex and damages it

Question 6

clinical features of adrenocortical failure *

Answer 6

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)

Question 7

what do the adrenal glands look like when affexted by autoimmune?

Answer 7

atrophic - they have shrunk

medulla is normal - not affected by ACTH or autoimmune

Question 8

appearance of adrenal gland affected by TB

Answer 8

granulomatous

cortex cant work - destroyed by the granulomas

Question 9

appearance of the adrenals when affected by cancer

Answer 9

metastasis present

but cortex cant work

Question 10

describe pro-opio-melanocortin *

Answer 10

synthesised in the pit

broken down to ACTH and MSH and endorphins and enkephalins and other peptides

(reason for pigmentation in Addison’s)

Question 11

consequence of adrenocorticoid failure *

Answer 11

eventual death because of low Na - Addisonian crisis

Question 12

how would you diagnose addison’s *

Answer 12

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

Question 13

describe the 9am cortisol test *

Answer 13

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

Question 14

descrube the synacthen test *

Answer 14

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

Question 15

describe congenital adrenal hyperplasia *

Answer 15

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

Question 16

describe complete 21-hydroxylase deficiency *

Answer 16

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

Question 17

what is the effect of raised sex steroids in congential adrenal hyperplasia *

Answer 17

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

Question 18

age of presentation of complete 21-hydroxylase deficiency |*

Answer 18

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

Question 19

describe PARTIAL 21-hydroxylase deficiency *

Answer 19

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

Question 20

describe 11-dehydroxylase deficiency *

Answer 20

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

Question 21

describe the action of 11-deoxycorticosterone and effect when it is in excess *

Answer 21

acts like aldosterone (is a mineralocorticoid)

therefore cause Na and water retention and K excretion

in excess casue hypertension and hypokalaemia

Question 22

describe 17-hydroxylase deficiency *

Answer 22

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)

Question 23

how do you investigate postural hypotension*

Answer 23

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

Question 24

casues of postural hypotension

Answer 24

due to hypovolaemia - eg haemorrhage

or ANS problem not sensing change in BP so not causing vasoconstiction

Question 25

what is an Addisonian crisis *

Answer 25

when addison’s disease is left untreated, the adrenal hormones get really low until you go into addisonian crisis

Question 26

what are the signs of the addisonian crisis *

Answer 26

severe dehydration

pale, cold, clammy skin

sweating

rapid, shallow breathing

dizziness

severe vomiting and diarrhoea

severe muscle weakness

headache

severe drowsiness or loss of consciousness

Question 27

how woukd you diagnose 21-hydroxylase CAH *

Answer 27

see if there is elevated 17 hydroxyprogesterone

short synacthen test - if cortisol doesnt go up to 450 - you fail, there will also be an exaggerated response of 17 hydroxyprogesterone - it will go above 30

look at genotype for mutations in the hydroxylase gene - it is autosomal recessive

urine steroid profile - see what break down products of enzymes are present to see if there are any other mutations