Hypoadrenal disorders

Question 1

What are the overarching causes of adrenocorticol failure

Answer 1

Enzymes in the steroid synthetic pathway are not working

Adrenal glands are destroyed

Question 2

What are the common causes of adrenocortical failure

Answer 2

Tuberculous Addison’s disease (world)
Autoimmune Addison’s (uk)
Congenital adrenal hyperplasia

Question 3

What are the clinical features of adrenocortical failure

Answer 3

fall in blood pressure
Loss of salt via the urine
Increased plasma potassium
Fall in glucose due to glucocorticoid deficiency 
Fatigue
Weight loss 
High ACTH resulting in increased pigmentation
Severe hypotension -> death

Question 4

What causes tanning in primary adrenocortical failure

Answer 4

pro-opio melanocortin is synthesised in the pituitary and broken down to ACTH and MSH (+endorphins + enkephalins + peptides)
As ACTH Increases, more MSH is made and therefore more melanin -> tanning

Question 5

What are the tests for Addisons

Answer 5

Short synACTHen test
Give 250 ug synacthen intra-muscularly
Measure cortisol response

Question 6

What are the cortisol levels for a typical Addison’s patient at 9am and 9:30

Answer 6

9am = 100 (270-900)

Synacthen administered IM

9:30 = 150 (>600)

Question 7

What is the commonest cause of congenital adrenal hyperplasia

Answer 7

21-hydroxylase deficiency

Question 8

Which hormones are deficient in 21-hydroxylase deficiency and why

Answer 8

Aldosterone and cortisol

Interruptions:
Progesterone -> 11 deoxycorticosterone
17OH progesterone -> 11 deoxycortisol

Question 9

Describe complete 21-hydroxylase deficiency

Answer 9

Aldosterone and cortisol absent
Sex steroids and testosterone in excess
Survival = <24 hours

Question 10

What is the age of presentation for complete 21-hydroxylase deficiency

Answer 10

As a neonate (salt losing addisonian crisis)
Before birth the foetus receives steroids across the placenta
Girls may have ambiguous genitalia (virilised by adrenal testosterone)

Question 11

Describe partial 21-hydroxylase deficiency

Answer 11

Cortisol and aldosterone are deficient
Sex steroids and testosterone are in excess
Present at any age they survive
Later life - hirsutism and virilisation in girls and precocious puberty in boys due to adrenal testosterone

Question 12

What is the significance of 11 deoxycorticosterone

Answer 12

Behaves like aldosterone

In excess it causes hypertension and hypokalaemia

Question 13

Describe 11-hydroxylase deficiency

Answer 13

Cortisol and aldosterone deficient
Sex steroids, testosterone an d11-deoxycorticosterone in excess
Virilisation, hypertension and Lowe potassium

Question 14

Describe 17-hydroxylase deficiency

Answer 14

Cortisol and sex steroids are deficient
11-deoxycorticosterone and aldosterone in excess
Hypertension, low potassium, sex steroid deficiency and glucocorticoid deficiency (low glucose)

Question 15

What is the common precursor for steroid hormone synthesis

Answer 15

Cholesterol (+pregnenolone)

Question 16

Describe the process of aldosterone production

Answer 16

1. Cholesterol
2. Progesterone
   21
3. 11 deoxycorticosterone
   11
4. Corticosterone
   18
5. Aldosterone

Question 17

Describe the process of cortisol production

Answer 17

1. Cholesterol
2. Progesterone
   17
3. 17 OH progesterone
   21
4. 11 deoxycortisol
   11
5. cortisol