Adrenal disorders - Addison's

Question 1

What is a steroid made from?

Answer 1

Cholesterol

Question 2

Where in the adrenal gland is cortisol made?

Answer 2

Zona fasciculata

Question 3

What is the effect of angiotensin II on adrenal glands?

Answer 3

Activates pathway from cholesterol to aldosterone + cortisol, by activating side-chain cleavage enzymes (hydroxylase enzymes)

Question 4

What are the three actions of aldosterone?

Answer 4

Control blood pressure, sodium levels and lowers potassium concentration

Question 5

What is the effect of ACTH on adrenal glands?

Answer 5

Activates pathway from cholesterol to aldosterone + cortisol, by activating side-chain cleavage enzymes (hydroxylase enzymes). Binds to zona fasciculata

Question 6

What is the difference between angiotensin II and ACTH’s effect on adrenal glands?

Answer 6

Angiotensin II activates 18-hydroxylase, ACTH activates 17-hydroxylase

Question 7

What are the key hydroxylases in the steroid synthesis pathway?

Answer 7

17 -> 21 -> 11 (cortisol)
21 -> 11 -> 18 (aldosterone)
From progesterone

Question 8

What are the two acquired ways primary adrenal failure occurs?

Answer 8

Autoimmune Destruction, Tuberculosis

Question 9

What is Addison’s disease?

Answer 9

When your adrenal gland does not produce enough steroid hormones aka primary adrenal failure
causes xs ACTH from pituitary due to negative feedback

Question 10

What are the three signs of Addison’s disease?

Answer 10

Increased pigmentation, autoimmune vitiligo (white patches), low blood pressure

Question 11

Why do Addison’s patients have a good tan?

Answer 11

Pro-opio-melanocortin (POMC) is released as a precursor to ACTH. Splits into ACTH and MSH (causes pigmentation)

Question 12

Where do congenital cause of adrenocortical failure affect?

Answer 12

Hydroxylase enzymes not working in steroid synthesis pathway

Question 13

Causes of adrenocortical failure

Answer 13

• TB addison’s (most common)
• Autoimmune addison’s (UK common)
• Congenital adrenal hyperplasia

Question 14

What is the structural change adrenal glands go under in congenital adrenocortical failure and why?

Answer 14

Adrenal hyperplasia - adrenal glands don’t make enough cortisol, pituitary makes more ACTH to increase adrenal gland performance

Question 15

What are the 6 presentations of adrenocortical failure?

Answer 15

Fatigue, breathlessness, vomiting, weight loss, postural hypotension, tanned

Question 16

What are the 6 physiological consequences of adrenocortical failure?

Answer 16

Low blood pressure, low sodium (most important), high potassium, low glucose, high ACTH, loss of salt in urine

Question 17

What is the eventual cause of death in untreated adrenocortical failure?

Answer 17

Severe hypotension

Question 18

What is made in the adrenal cortex

Answer 18

Corticosteroids

Question 19

3 types of corticosteroids

Answer 19

Mineralocorticoids, aldosterone
Glucocorticoids, cortisol
sex steroids, androgens and oestrogens

Question 20

What are the three tests for Addison’s disease?

Answer 20

9am cortisol - low,
ACTH - high,
short synACTHen test (ACTH) - cortisol will go up if normal
- no response with addison’s

Question 21

Why would you not give aldosterone injections?

Answer 21

Half-life of aldosterone is too short (would require lots of injections all day)

Question 22

Treatment of primary adrenocortical failure

Answer 22

Replacement of cortisol and aldosterone
Hydrocortisone, prednisolone, fludrocortisone

Question 23

What is used instead of aldosterone injections

Answer 23

Fludrocortisone
longer acting than aldosterone, agonist for mineralocorticoid receptor

Question 24

What is the problem with hydrocortisone?

Answer 24

Oral hydrocortisone - short half life, so would need to give thrice daily

Question 25

What is the solution to hydrocortisone?

Answer 25

Dehydrogenate to form prednisolone

Question 26

Why is prednisolone given less frequently than hydrocortisone?

Answer 26

Longer half life and stronger potency (7x) - only 3mg needed

Question 27

What enzyme is missing in congenital adrenal hyperplasia?

Answer 27

21 hydroxylase
Can be complete or partial

Question 28

In complete deficiency, which hormones will be absent, and which will be in excess?

Answer 28

Aldosterone and cortisol absent,
sex steroids and testosterone in excess (bc test doesnt need 21-OH)

Question 29

How long can you survive with complete deficiency

Answer 29

Babies present within 1-3 weeks with a salt-losing crisis
In utero the foetus gets steroids across the placenta

Question 30

How is the presentation for complete deficiency?

Answer 30

Girls - born with ambiguous genitalia (virilised from testosterone), Boys - often missed

Question 31

Partial deficiency

Answer 31

Cortisol and aldosterone deficient
Excess sex steroids
present at any age they survive

Question 32

How is partial deficiency detected?

Answer 32

Girls - hirsutism (hair) and virilisation // Boys - precocious (very early) puberty due to adrenal testosterone

Question 33

In 11-hydroxylase deficiency, what molecule takes over the role of aldosterone and what are the symptoms?

Answer 33

11-deoxy-corticosterone // Hypertension, Hypokalaemia

Question 34

What is the key difference in 17-hydroxylase deficiency compared to the other two?

Answer 34

Sex steroids and testosterone are also inhibited,
present low virility, fertility, no puberty etc.

Question 35

17 hydroxylase deficiency

Answer 35

cortisol and sex steroid deficient
aldosterone and 11 deoxycorticosterone in excess
hypertension, low K, sex steroid def, cortisol def