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 cholesterol 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

18-hydroxylase

Question 7

State 3 causes of adrenocortical failure.

Answer 7

Tuberculous Addison’s Disesae (commonest worldwide)
Autoimmune Addison’s Disease (commonest in the UK)
Congenital Adrenal Hyperplasia

Question 8

State 9 consequences of adrenocortical failure.

Answer 8

Postural Hypotension (due to lack of aldosterone) 
Hyperkalaemia 
Exhaustion
Weight loss
Hyponatraemia
Fall in glucose (due to lack of cortisol) 
Pigmentation (due to high ACTH)
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 (predisposition)

Question 10

Why does Addison’s cause skin pigmentation?

Answer 10

Lack of cortisol stimulates production of huge amounts of ACTH.
ACTH is formed from cleavage of POMC to ACTH + alpha-MSH
High ACTH also means high alpha-MSH, which stimulates melanocytes, causing skin pigmentation

Question 11

State some tests for Addison’s disease.

Answer 11

9 am cortisol = low
ACTH = high
Short synACTHen test (250 ug IM) = won’t make cortisol as cortex can’t respond

Question 12

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

Answer 12

21-hydroxylase deficiency

Question 13

What are the 2 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 + 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

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 there is 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.
Survive <24 hours if untreated

Question 18

What are the 2 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

Present later because they don’t have a salt losing Addisonian crisis.
Present once they start to see the effects of the excess adrenal sex steroids e.g. hirsuitism + precocious puberty
Also slightly hypotensive

Question 20

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

Answer 20

11-deoxycorticosterone accumulates
which has mineralocorticoid effects, thus no salt losing Addisonian crisis
Behave as if they have HIGH aldosterone
HYPERTENSIVE + HYPOKALAEMIC
There will still be some funnelling towards the sex steroid synthesis pathway causing virilisation

Question 21

Describe and explain the presentation of 17-hydroxylase deficiency.

Answer 21

High levels of aldosterone = hypertension + hypokalaemia
Lack cortisol + sex steroids so they will not go through puberty
Present ~pubertal age: hypertensive, hypoglycaemia, absent puberty + prone to infections because cortisol is needed to cope with the stress of infections

Question 22

What are the 3 “branches” of hormones produced by the adrenal cortex?

Answer 22

Mineralocorticoids: Aldosterone
Glucocorticoids: Cortisol
Sex steroids: Testosterone + Estradiol

Question 23

What would the adrenal glands look like in autoimmune Addisons, TB and metastasis?

Answer 23

AI: Atrophied adrenals, very small
TB: Granulomatous infiltration
Metastasis: Large tumour

Question 24

What would you expect to see in a blood test of a patient with Adrenocortical failure?

Answer 24

Low Na+

High K+

Question 25

List 4 features of partial 21-hydroxylase deficiency

Answer 25

Male pattern balding
Hirsutism
Irregular menstruation
Clitoral enlargement

Question 26

Why do babies with congenital adrenal hyperplasia have enlarged adrenals?

Answer 26

ACTH is raised to drive the adrenal cortex to produce its steroids, but only sex steroids can be produced
Excess ACTH makes adrenals grow