Hypoadrenal Disorders

Question 1

How many carbon atoms does cholesterol have?

Answer 1

27

Question 2

What determines which steroids the different parts of the adrenal gland produce?

Answer 2

The combination of enzymes present in the different parts of the adrenal gland – hydroxylation in different positions of the cholesterol molecule gives different products.

Question 3

Which enzyme converts cholesterol to pregnenolone?

Answer 3

Cytochrome P450 (short chain cleavage)

Question 4

Which sets of enzymes are switched on by ACTH?

Answer 4

Cortisol synthesis enzymes

Sex steroid synthesis enzymes

Question 5

The pituitary gland produces ACTH in response to what?

Answer 5

Stress

Question 6

Which enzyme converts corticosterone to aldosterone?

Answer 6

Aldosterone synthase (includes 18-hydroxylase)

Question 7

State three causes of adrenocortical failure.

Answer 7

Tuberculous Addison’s Disesae – most common cause worldwide
Autoimmune Addison’s Disease – most common cause in the UK
Congenital Adrenal Hyperplasia

Question 8

State some consequences of adrenocortical failure.

Answer 8

Hypotension (due to lack of aldosterone)
Hyperkalaemia
Loss of salt (sodium) in urine
Fall in blood glucose (due to lack of cortisol)
High ACTH –> pigmentation
Vitiligo
Eventual death due to severe hypotension

Question 9

Why do Addison’s patients get vitiligo?

Answer 9

Vitiligo is an autoimmune disease where you have antibodies against melanin
Autoimmune diseases tend to go hand-in-hand

Question 10

Why does Addison’s cause skin pigmentation?

Answer 10

The lack of cortisol stimulates the production of huge amounts of ACTH.
ACTH is formed from the cleavage of POMC (pro-opiomelanocortin) to ACTH and alpha-MSH High ACTH also means high alpha-MSH –> skin pigmentation

Question 11

State some tests for Addison’s disease.

Answer 11

9 am cortisol (this should be high in a normal person)
You could measure ACTH and this should be high in Addison’s Inject synthetic ACTH (synacthen) and if they have functioning adrenals, they should start to produce cortisol
NOTE: 250 mg IM synacthem

Question 12

What is the most common cause of congenital adrenal hyperplasia (CAH)?

Answer 12

21-hydroxylase deficiency

Question 13

What are the two degrees of CAH?

Answer 13

Partial or Complete (absence of the enzyme)

Question 14

Why are foetuses with CAH normally fine in utero?

Answer 14

In utero, the foetus’ will have maternal cortisol and aldosterone so don’t need to rely on their own endogenous production.

Question 15

Which hormones are absent in complete 21-hydroxylase deficiency?

Answer 15

Cortisol and Aldosterone

Question 16

What effect does 21-hydroxylase deficiency have on sex steroid synthesis?

Answer 16

It funnels the precursors towards the steroid synthesis pathway so you get an increase in adrenal sex steroids.

Question 17

What will happen to a baby with complete 21-hydroxylase deficiency after they are born?

Answer 17

They will have a salt losing Addisonian crisis due to the lack of aldosterone.

Question 18

What are the two main features of 21-hydroxylase deficiency?

Answer 18

Hypotension

Virilisation (female babies will be born with ambiguous genitalia)

Question 19

Describe the presentation of partial 21-hydroxylase deficiency.

Answer 19

They may present much later because they don’t have a salt losing Addisonian crisis.
They will present once they start to see the effects of the excess adrenal sex steroids e.g. hirsuitism and precocious puberty They will also be a little hypotensive

Question 20

Describe and explain the presentation and explanation of complete 11-hydroxylase deficiency.

Answer 20

With 11-beta hydroxylase deficiency there will be a build up of 11-deoxycorticosterone
11-deoxycorticosterone has mineralocorticoid effects so they don’t have a salt losing Addisonian crisis – they will behave as if they have HIGH aldosterone
They will be HYPERTENSIVE and HYPOKALAEMIC
There will still be some funnelling towards the sex steroid synthesis pathway so the child will also be VIRILISED
NOTE: boys may be missed because they tend to look normal

Question 21

Describe and explain the presentation of 17-hydroxylase deficiency.

Answer 21

They will have high levels of aldosterone meaning that they are hypertensive and hypokalaemic
They are missing cortisol and sex steroids so they will not go through puberty
They will usually present around pubertal age – they will be hypertensive, have borderline hypoglycaemia and absent puberty
NOTE: they will also have a lot of infections because you need cortisol to cope with the stress of infections