7. Hypoadrenal disorders Flashcards

1
Q

where are corticotrophin releasing hormone and adrenocorticotrophin hormone (corticotrophin) produced?

A

corticotrophin releasing hormone (CRH) - hypothalamus

adrenocorticotrophin hormone (corticotrophin) - pituitary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what is cholesterol converted to and where?

A

pregnenolone

converted by enzymes in the zona glomerulosa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

how is cholesterol converted to aldosterone?

A

in the cortex by adding OH groups in various positions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

why is the glucocorticoid route different to the mineralocorticoid route?

A

the glucocorticoid route is different because the zona fasciculata has slightly different enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

outline the conversion of cholesterol to aldosterone

A

cholesterol -> pregnenolone -> progesterone -> 11-deoxycorticosterone -> corticosterone -> aldosterone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

outline the conversion of cholesterol to cortisol

A

cholesterol -> pregnenolone -> progesterone -> 17𝛼-hydroxyprogesterone -> 11-deoxycortisol -> cortisol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

outline the conversion of cholesterol to 17𝛽-oestradiol

A

cholesterol -> pregnenolone -> 17𝛼-hydroxypregnenolone -> 17𝛼-hydroxyprogesterone -> androstenedione -> testosterone ->1 7𝛽-oestradiol (⇄ oestrone)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what does P450scc do?

A

it is the enzyme involved in side chain cleavage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what are glucocorticoid synthesis enzymes and sex steroid synthesis enzymes turned on by?

A

ACTH (pituitary detects stress and produces ACTH to make more cortisol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what are the causes of adrenocortical failure?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are the signs and symptoms of addison’s disease?

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what is the link between adrenal failure and increased pigmentation?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what is the test for addison’s?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what signs do a typical addison’s patient show after testing for addison’s?

A

low 9am cortisol (normal is 270-900)

cortisol of 100 1/2 hour after administering synacthen (should be >600 in normal)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is congenital adrenal hyperplasia caused by and what does it present with?

A

commonly caused by 21-hydroxylase deficiency (complete or partial)

presents with hypotension and virilisation (development of male physical characteristics in females)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what is complete 21-hydroxylase deficiency?

A

aldosterone and cortisol are completely absent

17
Q

how does complete 21-hydroxylase deficiency present?

A

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
18
Q

what is the treatment of complete 21-hydroxylase deficiency?

A

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
19
Q

what is partial 21-hydroxylase deficiency?

A

aldosterone and cortisol are still absent but patient is born with just enough aldosterone and cortisol

20
Q

how does partial 21-hydroxylase deficiency present?

A

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
21
Q

what are the signs of partial 21-hydroxylase in females?

A
  • receding hair line/baldness
  • acne
  • facial hair
  • variable pigmentation
  • small breasts
  • clitoral enlargement
  • muscular arms and legs
  • facial flush
22
Q

what is 11-𝛽 hydroxylase deficiency?

A

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
23
Q

what do patients with 11-𝛽 hydroxylase deficiency present with?

A
  • hypertensive in childhood
  • hypokalaemic
  • virilisitation
24
Q

what is 17 hydroxylase deficiency?

A

RECESSIVE

  • high levels of aldosterone but are missing cortisol and sex steroids
  • aldosterone and 11-deoxycorticosterone are in XS
25
Q

what do patients with 17 hydroxylase deficiency present with?

A
  • hypertension
  • hypokalaemia
  • don’t go through puberty (sex steroid deficient)
  • borderline hypoglycaemia (lack of glucocorticoid stimulation)
  • susceptible to infection (cortisol deficient)