Cortisol Pathways

Question 1

Cortisol Synthesis

Answer 1

Cholesterol –> pregnenolone (17 hydroxylase) –> 17-hydroxy - pregnenolone –> 17-hydroxy-progesterone (21 hydroxylase) –> 11-DOC (11-beta hydroxylase) –> cortisol

Question 2

Aldosterone Synthesis

Answer 2

Cholesterol –> pregnenolone –> progesterone (21 hydroxylase) –> 11-deoxycorticosterone (11-beta hydroxylase) –> corticosterone –> aldosterone

Question 3

DHEA and Androstenedione Synthesis

Answer 3

pregnenolone (17 hydroxylase) –> 17-hydroxy - pregnenolone (17 hydroxylase) –> DHEA

Cholesterol –> pregnenolone –> progesterone (17 hydroxylase) –> 17-hydroxyprogesterone (17 hydroxylase) –> androstenedione

Question 4

17 Alpha Hydroxylase Def

Answer 4

Dec androgens

Dec cortisol

But aldosterone no affected so inc aldosterone

Results = ambiguous genitalia in XY and no secondary sex traits in XX + HTN and hypokalemia

Question 5

21 Hydroxylase Def

Answer 5

Dec cortisol and dec aldosterone

Androgens not affected so inc androgens

Results = virilization in XX and precocious puberty + dec BP, inc K+ and inc renin

Also inc precursor (17-hydroxy-progesterone)

Question 6

11 Beta Hydroxylase Def

Answer 6

Dec cortisol and dec aldosterone BUT make DOC which can stimulate aldosterone receptors

Still inc androgens

Results = XX virilization + HTN + hypokalemia

Question 7

What is a metyrapone test?

Answer 7

Metyrapone blocks 11-beta-hydroxylase thus no cortisol synthesis

This means no neg feedback on CRH –> ACTH

This will lead to ACTH surge detected by 17-hydroxycorticosteroid surge in urine if the HPA axis is intact

Used to see if HPA axis intact