Hypoadrenal disorders

Question 1

How many carbon atoms does cholesterol have?

Answer 1

27

Question 2

What enzyme converts cholesterol to pregnenolone and where is it found?

Answer 2

P450scc

Zona glomerulosa

Question 3

How can cholesterol be converted to aldosterone?

Answer 3

In the adrenal cortex.
Add OH groups in different positions.
Following conversion to pregnenolone, hydroxylate position 3, add further OH groups at different positions (21, 11 and 18), and oxidise further.

Question 4

What are all steroids derived from?

Answer 4

Cholesterol

Question 5

Where are glucocorticoids produced?

Answer 5

Zona fasciculata, because it has slightly different enzymes to the zona glomerulosa (which produces mineralocorticoids).

Question 6

Where are the sex steroid pathways present?

Answer 6

Ovaries

Testes

Question 7

What activates glucocorticoid synthesis enzymes and sex steroid synthesis enzymes?

Answer 7

ACTH

Question 8

What triggers ACTH release from the pituitary?

Answer 8

Stress

Question 9

What does ACTH release from the pituitary result in?

Answer 9

Cortisol production

Question 10

How is cortisol produced from pregnenolone?

Answer 10

Add OH groups at position 17, 21 and 11.

Question 11

What triggers aldosterone production?

Answer 11

Renin and angiotensin II activate enzymes in the mineralocorticoid pathway to make aldosterone.

Question 12

What is the most common cause of adrenal failure worldwide?

Answer 12

Tuberculous Addison’s disease- particularly occurs when the course of treatment is stopped prematurely.

Question 13

What is the most common cause of adrenal failure in the UK?

Answer 13

Autoimmune Addison’s disease- immune system mistakenly wipes out adrenal gland.

Question 14

When may adrenocortical failure occur?

Answer 14

When the adrenal glands are destroyed.

When enzymes in the steroid synthesis pathway are not working.

Question 15

What can cause adrenal failure, other than autoimmune and tuberculous Addison’s?

Answer 15

Congenital adrenal hyperplasia.

Question 16

What is congenital adrenal hyperplasia?

Answer 16

Patient is born with large adrenal glands.
Caused by enzyme deficiency- adrenals cannot make hormones properly.
Adrenals are therefore stimulated and become enlarged.

Question 17

What are the consequences of adrenal failure?

Answer 17

Fall in blood pressure (no aldosterone)
Loss of salt in urine (no aldosterone, rise in plasma potassium)
Increased plasma potassium
Fall in glucose (due to glucocorticoid deficiency)
High ACTH resulting in increased pigmentation
Eventual death due to severe hypotension (Addisonian crisis)

Question 18

Where is proopiomelanocortin (POMC) synthesised?

Answer 18

Pituitary

Question 19

What is POMC broken down into?

Answer 19

ACTH
MSH (melanocyte stimulating hormone)
Endorphins
Enkephalins
Other peptides

Question 20

What is the link between adrenal failure and hyperpigmentation?

Answer 20

No adrenal gland
No cortisol
No negative feedback
High ACTH
High MSH
Increased pigmentation

Question 21

In a typical Addison’s patient, what would you expect their 9am cortisol and ACTH levels to be compared to normal?

Answer 21

9am cortisol low (around 100, normal range is 270-900)

ACTH high

Question 22

How can Addison’s be tested for?

Answer 22

Administer 250mg i.m. synacthen to a patient with low 9am cortisol and high ACTH. Half an hour later, cortisol level will not have changed in Addison’s patient- can’t make cortisol despite large dose of ACTH, so adrenals are abnormal.

Question 23

What is the most common cause of congenital adrenal hyperplasia?

Answer 23

21-hydroxylase deficiency- can be complete or partial.

Question 24

What does complete 21-hydroxylase deficiency result in?

Answer 24

Complete aldosterone and cortisol deficiency.
Excess sex steroids (especially testosterone).
<24hrs survival.

Question 25

How do neonates present with 21-hydroxylase deficiency?

Answer 25

Salt-losing Addisonian crisis.

Girls might have ambiguous genitalia (virilised by adrenal testosterone).

Question 26

What does partial 21-hydroxylase deficiency result in?

Answer 26

Deficient cortisol and aldosterone, with sex steroids in excess.

Question 27

When does partial 21-hydroxylase deficiency present?

Answer 27

Can present at any age.

Question 28

What are the main problems caused by 21-hydroxylase deficiency?

Answer 28

Hirsutism
Virilisation in girls
Precocious puberty in boys- adrenal testosterone

Question 29

What is 11-beta hydroxylase deficiency?

Answer 29

High 11-deoxycorticosterone (active aldosterone receptor agonist).
Hypertensive in childhood.
Hypokalaemia.
Cortisol and aldosterone deficiency.
Sex steroids in excess.
Virilisation.
(No salt-losing crisis).

Question 30

What is 17-hydroxylase deficiency?

Answer 30

High aldosterone- hypertension and hypokalaemia.
Cortisol deficiency.
Sex steroid deficiency- no puberty.
Glucocorticoid deficiency- borderline hypoglycaemia.

Question 31

What are the consequences of adrenocortical failure?

Answer 31

Fall in blood pressure
Loss of salt in urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation
Eventual death due to severe hypotension
Craving salt