Adrenal pathway dysfunction

Question 1

What does the adrenal gland produce

Answer 1

Aldosterone
Cortisol
Androgens, oestrogen

Question 2

Why are the numbers on cholesterol important?

Answer 2

We name the enzymes based on which carbon atoms on cholesterol they affect

Question 3

What are the main actions of aldosterone?

Answer 3

Controls blood pressure
Retains sodium
Lowers potassium

Question 4

What hydroxylases are involved in making aldosterone?

Answer 4

21, 11 and 18

Question 5

What hydroxylases are involved in making cortisol?

Answer 5

17, 21,11

Question 6

What rhythm does Cortisol have?

Answer 6

Diurnal

Question 7

What is Addison’s disease?

Answer 7

Primary adrenal failure
Autoimmune
TB of the adrenal glands is the most common cause worldwide

Question 8

What are the symptoms of Addison’s?

Answer 8

Increase pigmentations
Autoimmune viitiligo
No cortisol or aldosterone so low blood pressure

Question 9

What are the three causes of Adrenocortical failure?

Answer 9

Congenital adrenal hyperplasia

TB Addison’s

Autoimmune Addison’s

Question 10

What is POMC?

Answer 10

Pro-opio-melanocortin

Question 11

Why does Addison’s cause a tan?

Answer 11

POMC is a large precursor protein that is cleaved to form a number of smaller peptides, including ACTH, MSH and endorphins

Thus people who have pathologically high levels of ACTH may become tanned

Question 12

How does Addison’s present acutely?

Answer 12

Fall in blood pressure
Loss of salt in the urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency
High ACTH resulting in increased pigmentation

Question 13

What are other symptoms of Addison’s?

Answer 13

Darkening of hair
Weight loss  - anorexia, diarrhoea, vomiting
Muscular weakness
Pigment accentuation at nipples
Vitiligo
Freckling
Mucous membrane pigmentation

Question 14

What is the treatment for Addison’s?

Answer 14

IV hydrocortisone

Oral steroid replacement

Question 15

What are the tests for Addison’s?

Answer 15

9am cortisol = low
ACTH = high
Short synACTHen test

Question 16

What is the Short synACTHen test?

Answer 16

Give 250 ug synACTHen
IM
Measure cortisol response

Question 17

What cortisol levels are seen on a typical Addison’s patient?

Answer 17

Cortisol at 9am = 100 (270-900)
Administer injection IM of synacthen
Cortisol at 9.30 = 150 (>600)nM
Levels will eventually go to 0 if left untreated

Question 18

Why can you not give a aldosterone tablet?

Answer 18

Half life of aldosterone is too short (20 mins) for safe once daily administration

Question 19

What do we give to replace aldosterone?

Answer 19

Fluorine does not exist in natural steroids, so its presence slows metabolism substantially.
Binds to both MR and GR

Fludrocortisone half life 3.5h and
effects seen for 18h.
50-100mcg once daily

Question 20

How do we replace cortisol?

Answer 20

Oral hydrocortisone

Has a short half life: too short for once daily administration

8am
12pm
5pm

Question 21

Why is oral hydrocortisone problematic?

Answer 21

Peaks are too high and harmful

Disrupts sleep

Question 22

What is used more commonly now to replace cortisol?

Answer 22

3-4mg of prednisolone once daily

Question 23

What is the problem with prednisolone?

Answer 23

Cannot get a 3mg tabled of predisonlone

Have to take 1mg x3
3 1/4 of a 5mg tablet

Question 24

Summaries the treatment of adrenal failure

Answer 24

Hydrocortisone three times daily (10 + 5 + 2.5)
OR
Prednisolone 3mg daily

Fludrocortisone 50 to 100 mcg daily

Question 25

What is congenital adrenal hyperplasia?

Answer 25

Commonest is caused by 21-hydroxylase deficiency (missing gene) Can be complete or partial Born without aldosterone and cortisol Survive in utero because mother gives steroids via placenta

Question 26

What happens before birth?

Answer 26

Huge adrenal glands | High ACTH production

Question 27

How do you treat congenital adrenal hyperplasia?

Answer 27

Replacement

Question 28

What also happens in congenital adrenal hyperplasia?

Answer 28

Make huge amount of sex steroids In females Virilised by adrenal testosterone - labial fusion - ambiguous genitalia In males Missed as there is no obvious visual presentation

Question 29

How long can you survive with complete 21 hydroxyls deficiency?

Answer 29

Less than 24 hours without treatment

Question 30

What does partial 21 hydroxylase deficiency mean?

Answer 30

Partial 21 hydroxylase deficiency means that there will be a bit of aldosterone and cortisol to get by with Large excess of testosterone

Question 31

When do patients with partial 21 hydroxylase present?

Answer 31

At any age | Go through precocious puberty

Question 32

What are the main features of partial 21 hydroxylase deficiency in later life?

Answer 32

Main problem in later life is hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone

Question 33

What are features of females with partial 21 hydroxylase deficiency?

Answer 33

``` Small breasts Facial hirsutism Receding hair line baldness Male escutcheon Heavy muscular appearance ```

Question 34

What happens with 11 hydroxylase deficiency?

Answer 34

11 deoxycorticosterone behaves like aldosterone In excess it can cause hypertension and hypokalaemia

Question 35

What hormones are in excess with 11 hydroxylase deficiency?

Answer 35

Sex steroids and testosterone and 11-deoxycorticosterone

Question 36

What are the problems with 11 hydroxylase deficiency?

Answer 36

Virilisation, hypertension and low K

Question 37

What happens with 17 hydroxylase deficiency?

Answer 37

11-deoxycorticosterone and aldosterone (mineralocorticoids)

Question 38

What are the problems with 17 hydroxylase deficiency?

Answer 38

Hypertension, low K, sex steroid deficiency (no puberty) and glucocorticoid deficiency (low glucose).

Question 39

What are the treatments for congenital adrenal hyperplasia?

Answer 39

Single morning does of prednisolone 3mg is the equivalent dose to 20mg of hydrocortisone