ADRENAL FAILURE

Question 1

Detail where all the adrenal hormones are made

Answer 1

Mineralocorticoids (aldosterone) - glomerulosa
Glucocorticoids (cortisol) - fasciculata
Sex steroids (androgens/oestrogens) - fasciculata/reticularis
Catecholamines - medulla

Question 2

Which enzymes does angiotensin II activate?

Answer 2

Side chain cleavage
3 hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
18 hydroxylase

Question 3

Which enzymes foes ACTH activate?

Answer 3

Side chain cleavage
3 hydroxysteroid dehydrogenase
21 hydroxylase
11 hydroxylase
17 hydroxylase

Question 4

What is Addison’s disease?

Answer 4

Primary adrenal failure destroying adrenal cortex.

Lack of aldosterone and cortisol

Question 5

What are the causes of Addison’s?

Answer 5

Autoimmune (most common in UK)
Tuberculosis infection (most common worldwide)
Congenital adrenal hyperplasia

Question 6

What are some symptoms (including clinical) of Addison’s?

Answer 6

Increased pigmentation (high MSC)
Autoimmune vitligo
Low blood pressure
Salt in urine
Increased plasma potassium
Fall in blood glucose (glucocorticoid def)
High ACTH

Eventual death due to severe hypotension

Question 7

What are some tests for Addison’s?

Answer 7

9 am cortisol
blood ACTH test
Short synacthen test

Question 8

What is the short synacthen test?

Answer 8

Measure cortisol at 9:00am
Give injection of synacthen (synthetic ACTH)
Measure cortisol at 9:30am

If Addison’s, patient won’t respond and serum cortisol will remain similar

Question 9

What are the treatments for adrenal failure?

Answer 9

Fludrocortisone 50-100 mcg daily

Prednisolone 2-4mg once daily

Question 10

What is fludrocortisone and why do we use it?

Answer 10

Same as aldosterone but has a F instead of H on one of the carbons. This slows its metabolism and thus has a longer half-life (3.5hrs) and longer lasting effects (18hrs)

Question 11

What is prednisolone and why do we use it?

Answer 11

Same as cortisol but has C double bond. This means it has a longer half life and is more potent than cortisol (2.3x binding affinity)

Cannot give oral hydrocortisone (medical cortisol) because its half life too short so have to administer 3 times daily. This causes 3 peaks throughout the day which are harmful

Prednisolone mimics the diurnal/circadian rhythm

Question 12

What is congenital adrenal hyperplasia’s commonest cause?

Answer 12

21-hydroxylase deficiency

Question 13

Explain what complete and partial congenital adrenal hyperplasia is

Answer 13

Complete - missing gene for 21-hydroxylase

Partial - mutated gene for 21-hydroxylase

Question 14

Which hormones will be fully absent in complete congenital adrenal hyperplasia?

Answer 14

aldosterone

cortisol

Question 15

How long can a baby survive once born with complete congenital adrenal hyperplasia without treatment?

Answer 15

< 24 hrs because salt-losing addisonian crisis

Question 16

Which hormones will be in excess in congenital adrenal hyperplasia?

Answer 16

sex steroids e.g. testosterone which in girls will cause ambiguous genitalia

Question 17

Why won’t a foetus with congenital adrenal hyperplasia die before it is born?

Answer 17

It is supplied with steroids/lacking hormones via placenta from mother

Question 18

What are the main problems with partial congenital adrenal hyperplasia?

Answer 18

Hirsutism and virilisation in girls later in life

Precocious puberty in boys due to excess testosterone

Question 19

What does 11-hydroxlase deficiency cause?

Answer 19

No cortisol or aldosterone
Excess sex steroids and 11-deoxycorticosterone

11-deoxycorticosterone acts similar to aldosterone so excess causes hypertension and hypokalaemia

Question 20

What does 17-hydroxlase deficiency cause?

Answer 20

No cortisol or sex steroids
Excess 11-deoxycorticosterone and aldosterone

Hypertension, hypokalaemia, sex steroid deficiency, glucocorticoid deficiency (low glucose)