7. Hypoadrenal disorders Flashcards
where are corticotrophin releasing hormone and adrenocorticotrophin hormone (corticotrophin) produced?
corticotrophin releasing hormone (CRH) - hypothalamus
adrenocorticotrophin hormone (corticotrophin) - pituitary
what is cholesterol converted to and where?
pregnenolone
converted by enzymes in the zona glomerulosa
how is cholesterol converted to aldosterone?
in the cortex by adding OH groups in various positions
why is the glucocorticoid route different to the mineralocorticoid route?
the glucocorticoid route is different because the zona fasciculata has slightly different enzymes
outline the conversion of cholesterol to aldosterone
cholesterol -> pregnenolone -> progesterone -> 11-deoxycorticosterone -> corticosterone -> aldosterone
outline the conversion of cholesterol to cortisol
cholesterol -> pregnenolone -> progesterone -> 17𝛼-hydroxyprogesterone -> 11-deoxycortisol -> cortisol
outline the conversion of cholesterol to 17𝛽-oestradiol
cholesterol -> pregnenolone -> 17𝛼-hydroxypregnenolone -> 17𝛼-hydroxyprogesterone -> androstenedione -> testosterone ->1 7𝛽-oestradiol (⇄ oestrone)
what does P450scc do?
it is the enzyme involved in side chain cleavage
what are glucocorticoid synthesis enzymes and sex steroid synthesis enzymes turned on by?
ACTH (pituitary detects stress and produces ACTH to make more cortisol)
what are the causes of adrenocortical failure?
tuberculosis addison’s disease - occurs when you stop a course of treatment early (MOST COMMON IN WORLD)
autoimmune addison’s disease - occurs when the immune system makes a mistake and wipes out the adrenal gland (MOST COMMON IN UK)
congenital adrenal hyperplasia - autosomal recessive disorder which means you’re born with bigger adrenal glands that have an enzyme deficiency so you can’t make hormones properly
what are the signs and symptoms of addison’s disease?
- fall in BP (no aldosterone) -> eventual death due to severe hypotension
- loss of salt in urine (less Na retention)
- increased plasma potassium (less K excretion)
- fall in glucose (glucocorticoid deficiency)
- increased pigmentation in mouth, hair and skin (due to high MSH)
- patches of vitiligo
what is the link between adrenal failure and increased pigmentation?
ACTH is made from POMC (pro-opio melanocortin) which has 2 compartments: ACTH and MSH (melanocyte stimulating hormone)
because there is no adrenal gland there is no cortisol, so there is no -ve feedback and lots of ACTH is released
high ACTH = high MSH = increased pigmentation
what is the test for addison’s?
measure the hormones at 9am (cortisol should be high)
if cortisol is low this may be addison’s
ACTH should therefore be really high
give injection of synthetic ACTH (250mg synacthen) - if adrenals are functioning they should produce cortisol
what signs do a typical addison’s patient show after testing for addison’s?
low 9am cortisol (normal is 270-900)
cortisol of 100 1/2 hour after administering synacthen (should be >600 in normal)
what is congenital adrenal hyperplasia caused by and what does it present with?
commonly caused by 21-hydroxylase deficiency (complete or partial)
presents with hypotension and virilisation (development of male physical characteristics in females)
what is complete 21-hydroxylase deficiency?
aldosterone and cortisol are completely absent
how does complete 21-hydroxylase deficiency present?
people present with congenital adrenal hyperplasia (CAH) by 1 week old
- sex steroids and testosterone will be in XS (due to XS 17-hydroxyprogesterone)
- girls may have ambiguous genitalia
- if there is ambiguity there is a risk of death because this is a sign of CAH
- in boy’s the genitalia is normal so CAH may be missed
what is the treatment of complete 21-hydroxylase deficiency?
the baby can survive for a day because of the mother’s cortisol and aldosterone
- after a day the baby loses consciousness and has salt-losing addisonian crisis -> give SALINE
- the baby is given hydrocortisone and fludrocortisone to replace aldosterone
what is partial 21-hydroxylase deficiency?
aldosterone and cortisol are still absent but patient is born with just enough aldosterone and cortisol
how does partial 21-hydroxylase deficiency present?
people present with CAH at any age as they don’t have addisonian crisis
- sex steroids and testosterone in XS
- hirsutism (hair growth) and virilisation (male physique) in girls in later life
- early puberty in boys due to adrenal testosterone
what are the signs of partial 21-hydroxylase in females?
- receding hair line/baldness
- acne
- facial hair
- variable pigmentation
- small breasts
- clitoral enlargement
- muscular arms and legs
- facial flush
what is 11-𝛽 hydroxylase deficiency?
RECESSIVE
- results in a build up of 11-deoxycorticosterone (active aldosterone receptor agonist)
- patients are technically deficient in both aldosterone and cortisol but behave like they have XS aldosterone
what do patients with 11-𝛽 hydroxylase deficiency present with?
- hypertensive in childhood
- hypokalaemic
- virilisitation
what is 17 hydroxylase deficiency?
RECESSIVE
- high levels of aldosterone but are missing cortisol and sex steroids
- aldosterone and 11-deoxycorticosterone are in XS
what do patients with 17 hydroxylase deficiency present with?
- hypertension
- hypokalaemia
- don’t go through puberty (sex steroid deficient)
- borderline hypoglycaemia (lack of glucocorticoid stimulation)
- susceptible to infection (cortisol deficient)
