Congenital Adrenal Hyperplasia Flashcards
Define congenital adrenal hyperplasia.
Inherited disorder of adrenal steroidogenesis.
Explain the pathophysiology for congenital adrenal hyperplasia.
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
What genes are affected in CAH?
CYP21A: 21a-hydroxylase
CYP11B1: 11b-hydroxylase
CYP17A: 17a-hydroxylase
Describe the histology in CAH?
Hyperplasia of the adrenal cortex
Disorganised architecture of cortices + medullae
What causes adrenal hyperplasia in CAH?
Low levels of cortisol leads to lack of negative feedback on the pituitary
Increased ACTH secretion
Adrenal hyperplasia + increased secretion of adrenal precursor steroids
Which form of CAH is most common? What are the other 2 types?
21B-hydroxylase deficiency: 95%
11B-hydroxylase deficiency: 5%
17a-hydroxylase deficiency: v rare
Explain the aetiology/risk factors for congenital adrenal hyperplasia.
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.
How do 60-70% of babies with 21-hydroxylase deficiency present?
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
What are the subtypes of 21B-hydroxylase deficiency congenital adrenal hyperplasia?
Classic:
Salt-wasting type
Non-Salt-wasting type (simple virilising)
Non-classic
Give 4 common symptoms/ signs in CAH
Hypoglycaemia
Adrenal crisis: D+V= dehydration
Failure to thrive
Hyperpigmentation in areas NOT exposed to sun
What are the signs and symptoms of simple viriliser classic congenital adrenal hyperplasia?
No signs of shock
M: Precocious puberty at 2-4y
F: Ambiguous genitalia
What is the ambiguous genitalia in females with 21-b hydroxyls CAH?
Pseudohermaphroditism:
Clitoromegaly and/ or male external genitalia
Uterus + ovaries present
What are the signs and symptoms of non-classic viriliser congenital adrenal hyperplasia?
Late onset
Normal external genitalia
Precocious puberty
Acne
F: hirsutism, oligoamenorrhoea + Infertility
How can the differing levels of steroids be remembered in each type of CAH?
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
How does blood pressure differ in each type of CAH?
21B: HYPOtension
11B-, 17a: HTN (because DOC has mineralocorticoid activity)
What are the signs and symptoms of 17a-hydroxylase deficiency congenital adrenal hyperplasia?
- M: pseudohermaphroditism- female external genitalia, no uterus. Intra-abdominal testes.
- F: normal external genitalia, primary amenorrhoea
BOTH: Delayed puberty/ sexual infantilism
HTN
Hypernatraemia
Hypokalaemia
What are the signs and symptoms of 11b-hydroxylase deficiency congenital adrenal hyperplasia?
HTN
Hypernatraemia
Hypokalaemia
M: Precocious puberty
F: Virilisation
What screening test can be used in newborns for CAH?
HIGH Serum conc. 17-hydroxyprogesterone (17OHP)
in 21B and 11B deficiency
What acid-base abnormalities can be seen in CAH?
21B: Metabolic acidosis
11B: Metabolic alkalosis
17B: Metabolic alkalosis
Which serum marker is only increased in 17a hydroxylase deficiency?
Corticosterone
What are the investigations for congenital adrenal hyperplasia?
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.
What is the management plan for acute salt-losing crisis?
IV 0.9% NaCl (20 ml/kg) over 1st hour + repeat as necessary,
IV Dextrose + hydrocortisone
Monitor for hypoglycaemia.
What is the management plan for classical simple viriliser type congenital adrenal hyperplasia?
Medical:
- Glucocorticoid (hydrocortisone)
- Growth hormone
Surgery: Genital surgery if required.
What is the management plan for classical salt-wasting form congenital adrenal hyperplasia?
Medical:
- Glucocorticoid: Hydrocortisone
- Mineralocorticoid: Fludrocortisone
- NaCl supplementation PRN
- Growth hormone
Surgery – Genital surgery if required.
When the patient is unwell, what needs to change in the management for congenital adrenal hyperplasia?
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.
What medication is needed in 11B and 17a hydroxyls deficiency?
Spironolactone to block mineralocorticoid receptors
Reduced dietary sodium intake
What are possible complications associated with congenital adrenal hyperplasia?
- Reduced female fertility.
- Short stature (premature epiphyseal closure secondary to steroid therapy).
- Steroid side effects.
What is the prognosis of congenital adrenal hyperplasia?
Good if diagnosed early.
Undiagnosed infants may die from salt-losing crises.
