Congenital Adrenal Hyperplasia

Question 1

Define congenital adrenal hyperplasia.

Answer 1

Inherited disorder of adrenal steroidogenesis.

Question 2

Explain the pathophysiology for congenital adrenal hyperplasia.

Answer 2

Autosomal recessive genetic defect in the cytochrome P450 (CYP) protein enzymes involved with adrenal steroidogenesis.
Results in:
Decreased levels of cortisol + aldosterone
Increased levels of precursor adrenocortical hormones causing Sx

Question 3

What genes are affected in CAH?

Answer 3

CYP21A: 21a-hydroxylase
CYP11B1: 11b-hydroxylase
CYP17A: 17a-hydroxylase

Question 4

Describe the histology in CAH?

Answer 4

Hyperplasia of the adrenal cortex
Disorganised architecture of cortices + medullae

Question 5

What causes adrenal hyperplasia in CAH?

Answer 5

Low levels of cortisol leads to lack of negative feedback on the pituitary

Increased ACTH secretion

Adrenal hyperplasia + increased secretion of adrenal precursor steroids

Question 6

Which form of CAH is most common? What are the other 2 types?

Answer 6

21B-hydroxylase deficiency: 95%
11B-hydroxylase deficiency: 5%
17a-hydroxylase deficiency: v rare

Question 7

Explain the aetiology/risk factors for congenital adrenal hyperplasia.

Answer 7

Phenotypical variance:

• Occult (clinically asymptomatic disease)
• Non-classic (adolescence/ adulthood mild form)
• Classic (severe infantile adrenal insufficiency +/-salt wasting and virilisation).
• 21-hydroxylase deficiency: Salt wasting/simple virilising/non-classic.

Consanguinity and family history are risk factors.

Question 8

How do 60-70% of babies with 21-hydroxylase deficiency present?

Answer 8

M: In first few weeks of life with SHOCK because of severe dehydration due to an adrenal crisis + salt wasting due to hypoaldosteroronism

F: Ambiguous genitalia

Question 9

What are the subtypes of 21B-hydroxylase deficiency congenital adrenal hyperplasia?

Answer 9

Classic:
Salt-wasting type
Non-Salt-wasting type (simple virilising)

Non-classic

Question 10

Give 4 common symptoms/ signs in CAH

Answer 10

Hypoglycaemia
Adrenal crisis: D+V= dehydration
Failure to thrive
Hyperpigmentation in areas NOT exposed to sun

Question 11

What are the signs and symptoms of simple viriliser classic congenital adrenal hyperplasia?

Answer 11

No signs of shock
M: Precocious puberty at 2-4y
F: Ambiguous genitalia

Question 12

What is the ambiguous genitalia in females with 21-b hydroxyls CAH?

Answer 12

Pseudohermaphroditism:
Clitoromegaly and/ or male external genitalia
Uterus + ovaries present

Question 13

What are the signs and symptoms of non-classic viriliser congenital adrenal hyperplasia?

Answer 13

Late onset
Normal external genitalia
Precocious puberty
Acne
F: hirsutism, oligoamenorrhoea + Infertility

Question 14

How can the differing levels of steroids be remembered in each type of CAH?

Answer 14

1 DOC: If deficient enzyme STARTs with 1 (11B-, 17a-): Increased 11-Deoxycorticosterone (DOC)

AND 1: If deficient enzyme ENDs with 1 (21B-, 11B-) ANDROGENs are increased

Question 15

How does blood pressure differ in each type of CAH?

Answer 15

21B: HYPOtension
11B-, 17a: HTN (because DOC has mineralocorticoid activity)

Question 16

What are the signs and symptoms of 17a-hydroxylase deficiency congenital adrenal hyperplasia?

Answer 16

• M: pseudohermaphroditism- female external genitalia, no uterus. Intra-abdominal testes.
• F: normal external genitalia, primary amenorrhoea

BOTH: Delayed puberty/ sexual infantilism
HTN
Hypernatraemia
Hypokalaemia

Question 17

What are the signs and symptoms of 11b-hydroxylase deficiency congenital adrenal hyperplasia?

Answer 17

HTN
Hypernatraemia
Hypokalaemia
M: Precocious puberty
F: Virilisation

Question 18

What screening test can be used in newborns for CAH?

Answer 18

HIGH Serum conc. 17-hydroxyprogesterone (17OHP)
in 21B and 11B deficiency

Question 19

What acid-base abnormalities can be seen in CAH?

Answer 19

21B: Metabolic acidosis
11B: Metabolic alkalosis
17B: Metabolic alkalosis

Question 20

Which serum marker is only increased in 17a hydroxylase deficiency?

Answer 20

Corticosterone

Question 21

What are the investigations for congenital adrenal hyperplasia?

Answer 21

Bloods: 17-hydroxyprogesterone, DOC, Corticosterone, Na, K

ACTH stimulation test confirms: Inappropriately elevated 17-hydroxyprogesterone levels after IM ACTH.

Pelvic USS: Presence of uterus/ PCOS/ renal anomaly.

Karyotype: Mutation location + chromosomal sex.

Question 22

What is the management plan for acute salt-losing crisis?

Answer 22

IV 0.9% NaCl (20 ml/kg) over 1st hour + repeat as necessary,

IV Dextrose + hydrocortisone

Monitor for hypoglycaemia.

Question 23

What is the management plan for classical simple viriliser type congenital adrenal hyperplasia?

Answer 23

Medical:
- Glucocorticoid (hydrocortisone)
- Growth hormone

Surgery: Genital surgery if required.

Question 24

What is the management plan for classical salt-wasting form congenital adrenal hyperplasia?

Answer 24

Medical:
- Glucocorticoid: Hydrocortisone
- Mineralocorticoid: Fludrocortisone
- NaCl supplementation PRN
- Growth hormone

Surgery – Genital surgery if required.

Question 25

When the patient is unwell, what needs to change in the management for congenital adrenal hyperplasia?

Answer 25

Doses of steroids should be increased when unwell.

Prednisolone + dexamethasone can also be used.

Aim of steroid therapy is to suppress enzyme level rather than to replace glucocorticoid so doses are relatively higher in CAH then in hypopituitarism or adrenal insufficiency.

Question 26

What medication is needed in 11B and 17a hydroxyls deficiency?

Answer 26

Spironolactone to block mineralocorticoid receptors
Reduced dietary sodium intake

Question 27

What are possible complications associated with congenital adrenal hyperplasia?

Answer 27

• Reduced female fertility.
• Short stature (premature epiphyseal closure secondary to steroid therapy).
• Steroid side effects.

Question 28

What is the prognosis of congenital adrenal hyperplasia?

Answer 28

Good if diagnosed early.

Undiagnosed infants may die from salt-losing crises.