Hypoadrenal disorders

Question 1

Describe cholesterol

Answer 1

See notes

Question 2

Which carbons must you add OH groups onto in pregnenolone to produce aldosterone and cortisol?

Answer 2

cortisol - 17, 21 and 11
aldosterone - 21, 11 and 18

Draw out diagram showing the simplified pathway.

Question 3

What does ACTH switch on?

Answer 3

Glucocorticoid synthesis enzymes and sex steroid enzymes

Question 4

What are the causes of adrenocortical failure?

Answer 4

Adrenal glands are destroyed (2):
Tuberculous Addison’s disease - most common cause of adrenalcortical failure worldwide
Autoimmune Addison’s disease - commonest in the UK

Enzymes in the steroid synthetic pathway not working (1):
Congenital adrenal hyperplasia - enzyme deficiency so high levels of ACTH which cause the adrenal glands to grow. trophic = grow

Question 5

Features of Addison’s disease

Answer 5

Lose weight, skin gets darker (tan), mouth gets darker (pigmentation), hypotension, tired fatigued, vitiligo

Skin gets darker - rising ACTH means increasing MSH = POMC –> ACTH + a-MSH
Vitiligo - autoimmune disease of the skin, antibodies against melanin

Question 6

Consequences of adrenocortical failure

Answer 6

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

Question 7

Describe the link between pigmentation and adrenalcortical failure

Answer 7

See notes

Question 8

How do you test for Addison’s disease?

Answer 8

1) Measure the levels or cortisol at 9 am - low
2) Measure the levels of ACTH - high
3) Short synACTHen test - give 250mg of synACTHen IM then measure for a cortisol response

See notes

Question 9

What is a typical Addison’s patient following a synACTHen test?

Answer 9

Cortisol at 9am = 100 (normal 270-900nM)
Administer injection of IM synACTHen
Cortisol at 9:30 = 150 (normal >600nM)

Question 10

Describe CAH

Answer 10

Commonest cause is by 21-hydroxylase deficiency.
It can be partial or complete. Think about which enzymes are missing using the diagram showing the production of different steroid hormones. Aldosterone and cortisol will be missing a drive towards the production of sex steroids. In a baby they will have exposed to high levels of androgens. If it is a girl they might have ambiguous genitalia - if you see this keep them in hospital give them normal saline and steroids. To prevent ambiguous genitalia in a girl you can give steroids to the mother if you know you’ve already got a child with CAH. It will cross the placenta.

A baby with 21-hydroxylase deficiency will have salt losing addisonian crisis after one day. 21-hydroxylase deficiency is recessive

Presentation of CAH: Virilisation and hypotension
See notes

Question 11

Describe partial 21-hydroxylase deficiency

Answer 11

Hirsuitism + virilisation in girls, precocious puberty in boys. Think about the hormones involved using the diagram

See notes + lecture

Question 12

Describe 11-hydroxylase deficiency

Answer 12

Think about hormones involved using the diagram. You get a build up of 11-deoxycorticosterone. Although aldosterone isn’t produced it binds to the aldosterone receptor –> hypertension and hypokalaemia
There are high sex steroids = virilisation

See notes + lecture

Question 13

Describe 17-hydroxylase deficiency

Answer 13

Cortisol and sex steroids deficient
11-deoxycortisone and aldosterone (mineralocorticoids) are in excess
As a result they will have hypertension (aldosterone), never go through puberty (no sex steroids).
See notes