Hypoadrenal disorders

Question 1

Recall the 4 possible causes of primary adrenal insufficiency, in order of decreasing prevalence worldwide

Answer 1

1. Addisons disease - TB
2. Addisons disease - AI
3. Congenital adrenal hyperplasia
4. Acute adrenal insufficiency

Question 2

Describe how an individual is tested for Addison’s disease

Answer 2

9am Cortisol level measured
If low: give synacthen intramuscularly
Re-measure cortisol, if below 600 is positive for Addison’s

Question 3

Where is the dysfunction in secondary adrenal insufficiency?

Answer 3

Adenohypophysis

Question 4

Recall the simplified synthesis of aldosterone from cholesterol, naming the enzyme in each step

Answer 4

Cholesterol 
(P450scc)
Pregnenolone
(3-beta-hydroxysteroiddehydrogenase)
Progesterone
(21-alpha-hydroxylase)
11-deoxycorticosterone
(11-alpha hydroxylase)
corticosterone
(18-alpha-hydroxylase)
Aldosterone

Question 5

Recall the simplified synthesis of cortisol from cholesterol, naming the enzyme in each step

Answer 5

Cholesterol 
(P450scc)
Pregnenolone
(3-beta-hydroxysteroiddehydrogenase)
Progesterone
(17-beta-hydroxysteroiddehydrogenase)
17-hydroxy-progesterone
(21-alpha-hydroxylase)
11-deoxycortisol
(11-alpha hydroxylase)
cortisol

Question 6

Recall the simplified synthesis of androgens and oestrogens from cholesterol, naming the enzyme in each step

Answer 6

Cholesterol 
(P450scc)
Pregnenolone
(3-beta-hydroxysteroiddehydrogenase)
Progesterone
(17-beta-hydroxysteroiddehydrogenase)
17-hydroxy-progesterone
--> sex steroids

Question 7

Recall which zone of the adrenals produces each different steroid

Answer 7

Z. Glomerulosa - Aldosterone
Z. Fasciculata - Cortisol
Z. Reticularis - sex steroids

Question 8

List and explain 5 clinical features of Addison’s disease

Answer 8

1. High pigmentation due to excess POMC cleavage
2. Hypotension due to lack of salt
3. Low sodium with high potassium due to loss of Na+/K+ exchanger
4. Fall in glucose due to GC and MC deficiency
5. Vitiligo (In AI disease)

Question 9

What is the main presenting feature of an Addisonian crisis?

Answer 9

Sudden severe hypotension

Question 10

What is the most common cause of congenital adrenal hyperplasia?

Answer 10

21-hydroxylase deficienct

Question 11

Recall the hereditary pattern of CAH

Answer 11

Always recessive

Question 12

Recall the clinical features for neonates (M and F) of complete absence of 21-alpha-H

Answer 12

In baby girls: virilisation; clitoromegaly, labial fusion

Often missed in boys: return to A&E as “floppy baby”

Question 13

What is “simple virilising congenital adrenal hyperplasia” and how does it present?

Answer 13

Partial loss of 21-alpha-H

Individuals survive, may present later with virilisation etc

Question 14

How does treatment of 11-alpha-H deficiency and 21-alpha-H deficiency differ and why?

Answer 14

In 11-alpha-H deficiency, 11-deoxycorticosterone is still produced and can replace aldosterone, so only the cortisol (and not aldosterone) needs to be replaced

Question 15

How and when do patients with an 11-alpha-hydroxylase deficiency usually present?

Answer 15

About 6 years old: virilisation and HYPERtension

Question 16

What is unusual about the presentation of 11-alpha-H deficiency compared to other congenital adrenal hyperplasias?

Answer 16

Have hypertension (rather than hypotension) as there is excess 11-deoxycorticosterone acting in the place of aldosterone

Question 17

What hormones will be deficient in 17-alpha-hydroxylase deficiency?

Answer 17

Cortisol, sex steroids

Question 18

Recall 2 features of 17-alpha-hydroxylase deficiency

Answer 18

1. No puberty

2. Low glucose due to GC deficiency

Question 19

Recall 2 medical treatment options for replacement of cortisol

Answer 19

Dexamethosone (1/day)

Hydrocortisone (2=3/day)

Question 20

Recall the 3 lines of treatment that are required in CAH

Answer 20

1. Replace cortisol
2. Replace aldosterone with salt-wasting analogue
3. Suppress ACTH to prevent over-production of adrenal androgens

Question 21

What drug is used to replace aldosterone in CAH?

Answer 21

Fludrocortisone

Question 22

What would show the glucocorticoid dosage in CAH treatment to be too high/low?

Answer 22

Too high –> Cushingoid

Too low –> hirsuitism

Question 23

What biochemical marker can be used to measure corticosterone replacement therapy?

Answer 23

17-hydroxy-progesterone

Question 24

What is it also important to bear in mind when administering cortisol-replacement therapy?

Answer 24

Dosage must be increased when patient is particularly vulnerable to stress

Question 25

How are patients managed pre-operatively if they have adrenal insufficiency?

Answer 25

o The anaesthetists need to give IV hydrocortisone before operation, and then at periods after their operation