Endocrinology: Congenital Adrenal Hyperplasia

Question 1

It is the most common non iatrogenic cause of insufficient cortisol and mineralocorticoid secretion. True or false?

Answer 1

True

Question 2

What causes it?

Answer 2

A number of autosomal recessive disorders of adrenal steroid biosynthesis

Question 3

Over 90% have a deficiency of what enzyme?

Answer 3

21-hydroxylase - it is needed for cortisol biosynthesis

Question 4

What percentage are also unable to produce aldosterone?

Answer 4

70-80%

Question 5

What does an inability to produce aldosterone lead to?

Answer 5

Salt loss and therefore hypovolaemia

Low sodium and high potassium

Question 6

In the fetus, the cortisol deficiency stimulates the pituitary to produce…

Answer 6

ACTH - this drives the overproduction of adrenal androgens

Question 7

How can it present?

Answer 7

Virilisation of the external genitalia in female infants with clitoral hypertrophy and variable fusion of the labia
In infant male - penis may be enlarged and scrotum pigmented (often only noticed when diagnosis made)
Salt losing adrenal crisis (in those who are salt losers)
Tall stature in the 20% of non salt losers, who also develop a muscular build, adult body odour, pubic hair, acne from excess androgens, leading to precocious pubarche

Question 8

Describe a salt losing adrenal crisis

Answer 8

Occurs at week 1-3 
Vomiting 
Weight loss
Hypotonia
Circulatory collapse 
A salt losing crisis is less common in girls as the virilisation is noted early and treatment started before salt loss significant

Question 9

Is there a complete of partial deficiency of hormones?

Answer 9

Can be either
Classic form = complete deficiency of aldosterone and cortisol, with raised androgens
Non classic = partial deficiency leading to near normal aldosterone and cortisol but elevated androgens

Question 10

Why do you get elevated androgens?

Answer 10

The precursors of aldosterone and cortisol build up and get funnelled into producing androgens

Question 11

How does aldosterone normally act on the kidney?

Answer 11

It acts on the distal nephron to increase sodium reabsorption, increase water reabsorption and increase potassium secretion

Question 12

Because there is low aldosterone, the RAAS system is activated and there are high levels of…

Answer 12

Renin

Question 13

What role does cortisol have on the liver?

Answer 13

Gluconeogenesis
If fasting occurs - cortisol stimulates the liver to produce and release glucose. Without cortisol, if fasting occurs = hypoglycaemia

Question 14

How do those with non classic form present?

Answer 14

No signs of salt wasting, but signs of high androgen e.g acne, hirsutism, irregular menses

Question 15

Usually CAH is due to 21 hydroxylase deficiency, but what else can cause it?

Answer 15

11 beta hydroxylase deficiency

Question 16

What may there be a neonatal history of?

Answer 16

Death if a salt losing crisis had not been recognised and treated

Question 17

How is it diagnosed?

Answer 17

Finding markedly raised levels of the metabolic precursor 17 alpha-hydroxy-progesterone in the blood 
In salt losers:
Low plasma sodium
High plasma potassium 
Metabolic acidosis
Hypoglycaemia

Question 18

How is it managed long term?

Answer 18

Lifelong glucocorticoids e.g hydrocortisone to suppress ACTH levels (and hence testosterone) to allow normal growth an maturation
Mineralocorticoids (fludrocortisone) if there is salt loss
Additional hormone replacement to cover illness or surgery, as they are unable to mount a cortisol response

Question 19

Definitive surgical reconstruction in affected females is usually delayed until…

Answer 19

Late puberty

Question 20

How is a salt losing crisis managed?

Answer 20

IV Sodium chloride
IV Glucose
IV Hydrocortisone

Question 21

What monitoring is required?

Answer 21

Monitoring of growth, skeletal maturity, plasma androgens and 17 alpha-hydroxy-progesterone
Insufficient hormone replacement results in increased ACTH secretion and androgen excess - this will cause rapid initial growth and skeletal growth at the expense of final height
Excessive hormone replacement will result in skeletal delay and slow growth