CAH and 21-hydroxylase deficiency

Question 1

How are CAH and 21-hydroxylase deficiency related to each other?

Answer 1

CAH = congenital adrenal hyperplasia, encompasses a range of disorders, but 90% of CAH is because of 21-hydroxylase deficiency

Question 2

Go through the pathophys of 21-hydroxylase deficiency, and how it leads to CAH. What is it’s usual mode of inheritance?

Answer 2

21-hydroxylase is an enzyme responsible for converting cholesterol into aldosterone and cortisol. 21-hydroxylase deficiency = less aldosterone and cortisol. It also means that the precursor molecules build up, and get shunted into the other steroid pathway to make excessive androgens. Autosomal recessive disorder.

The adrenal hyperplasia is because with decreased cortisol, there’s decreased repression of ACTH. Too much ACTH = hyperstimulation of adrenal glands = hyperplasia (it also contributes to excessive androgen production)

Question 3

Name the 3 main types of CAH

Answer 3

Salt-losing CAH
Non salt-losing CAH
Late onset CAH

Question 4

What happens in salt-losing CAH in terms of hormones? What do girls and boys look like?

Answer 4

High androgens, low cortisol and aldosterone (low aldosterone = salt-losing).

Girls - genital abnormalities from excess androgens (enlarged, fused labia, clitoris enlarged and looks like penis)

Boys - darkened genitals, and poor feeding, weight loss, vomiting (from hyponatraemia)

Question 5

What happens in non-salt-losing CAH in terms of hormones? What do girls and boys look like?

Answer 5

High androgens but normalish aldosterone (therefore don’t lose salt) - results from milder enzyme deficiency

Girls - clitoris looks like penis
Boys - often have big penis, early onset pubic hair

Question 6

What happens in late-onset CAH? What do girls and boys look like?

Answer 6

Most mild form of disease, often not recognised until puberty

Girls - rapid early growth, hirsutism, irregular periods
Boys - early beard growth, reduced fertility

Question 7

Name the 4 aspects of treatment of CAH

Answer 7

Restore Na and water balance
Avoid adrenal crisis
Maintain normoglycaemia
Optimise normal growth and development

Question 8

What two drugs are mostly used for CAH?

Answer 8

Hydrocortisone (replaces cortisol, but with the most minimal side effects)
Flurocortisone (replaces aldosterone if necessary)