7 - Hypoadrenal disorders

Question 1

What is meant by ‘trophic’?

Answer 1

to grow

stimulating the activity of another endocrine gland

Question 2

How many carbon atoms does cholesterol have?

Answer 2

27

Question 3

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

Answer 3

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 4

Which zones of the adrenal cortex produce what hormones?

Answer 4

zona glomerulosa - aldosterone (mineralocorticoid)
zona fasciculata - cortisol (glucocorticoid)
zona reticularis - sex hormones

Question 5

Which enzyme converts cholesterol to pregnenolone?

Answer 5

Cytochrome P450 (short chain cleavage)

Question 6

How is pregnenolone converted into progesterone?

Answer 6

oxidation (dehydrogenase enzymes)

Question 7

Which sets of enzymes are switched on by ACTH?

Answer 7

• Cortisol synthesis enzymes

- Sex steroid synthesis enzymes

Question 8

The pituitary gland produces ACTH in response to what?

Answer 8

Stress

Question 9

Structurally, how are testosterone and oestrodiol related?

Answer 9

they are isomers of each other

Question 10

What is P450 scc?

Answer 10

P450 enzyme that that performs side chain cleavage

Question 11

In what positions is pregnenolone hydroxylated in to become cortisol?

Answer 11

17, 21 and 11

Question 12

In what positions is pregnenolone hydroxylated in to become aldosterone?

Answer 12

21, 11, 18

Question 13

How is the aldosterone pathway regulated?

Answer 13

by the renin-angiotensin system

Question 14

Draw out the simplified diagram of the enzymes and molecules involved in the production of hormones in the adrenal cortex

Answer 14

(see OneNote)

Question 15

Which enzyme converts corticosterone to aldosterone?

Answer 15

Aldosterone synthase (includes 18-hydroxylase)

Question 16

State three causes of adrenocortical failure.

Answer 16

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

Question 17

State some consequences of adrenocortical failure

Answer 17

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 (Addisonian crisis)

Question 18

Why do Addison’s patients get vitiligo?

Answer 18

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

Question 19

Why does Addison’s cause skin pigmentation?

Answer 19

The lack of cortisol stimulates the production of huge amounts of ACTH.
ACTH is formed from the cleavage of POMC to ACTH and a-MSH
High ACTH also means high a-MSH —> skin pigmentation

Question 20

State some tests for Addison’s disease.

Answer 20

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

Question 21

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

Answer 21

21-hydroxylase deficiency

Question 22

What are the two degrees of CAH?

Answer 22

Partial or Complete (absence of the enzyme)

Question 23

Why are foetuses with CAH normally fine in utero?

Answer 23

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

Question 24

Which hormones are absent in complete 21-hydroxylase deficiency?

Answer 24

Cortisol and Aldosterone

Question 25

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

Answer 25

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

Question 26

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

Answer 26

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

Question 27

Which hormones will be in excess in complete 21-hydroxylase deficiency?

Answer 27

sex steroids and testosterone

Question 28

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

Answer 28

Hypotension | Virilisation (female babies will be born with ambiguous genitalia)

Question 29

Describe the presentation of partial 21-hydroxylase deficiency.

Answer 29

- may present much later because they don’t have a salt losing Addisonian crisis. - 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 30

What hormones are low/deficient in partial 21-hydroxylase deficiency?

Answer 30

cortisol and aldosterone NOTE: not to the same extent as in complete - can survive for a long time

Question 31

What hormones are in excess in partial 21-hydroxylase deficiency?

Answer 31

sex steroid and testosterone

Question 32

What age does partial 21-hydroxylase deficiency present at?

Answer 32

any age as they can survive with no intervention usually presents around the age of puberty e.g. hirsuitism and precocious puberty

Question 33

What steroid (intermediate) builds up in 11β hydroxylase deficiency? What impact does this have?

Answer 33

build up of 11-deoxycorticosterone, which is an active aldosterone receptor agonist i.e. the person behaves as though they have a high level of aldosterone

Question 34

What hormones is there an excess of in 11β hydroxylase deficiency?

Answer 34

sex steroids and testosterone

Question 35

What are the clinical features of 11β hydroxylase deficiency?

Answer 35

hypertensive and hypokalaemic children will be virilised because there is a high level of sex steroids (still be some funnelling towards the sex steroid synthesis pathway) NOTE: boys may be missed because they tend to look normal

Question 36

What hormones will there be an excess of in 17β-hydroxylase deficiency?

Answer 36

aldosterone

Question 37

What hormones will be deficient in 17β-hydroxylase deficiency?

Answer 37

cortisol and sex steroids

Question 38

What are the problems associated with 17β-hydroxylase deficiency?

Answer 38

hypertension hypokalaemia sex steroid deficiency glucocorticoid deficiency - borderline hypoglycaemia have more infections because you require more cortisol to deal with the stress of infection

Question 39

When do people with 17β-hydroxylase deficiency usually present?

Answer 39

usually present around the pubertal age (the ovaries, testes and the adrenal glands are not producing sex steroids)