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 and aldosterone and increased levels of precursor adrenocortical hormones cause symptoms (e.g. increased deoxycorticosterone leads to sodium retention/HT at supraphysiological levels).
Encoding genes: CYP21A (21a-hydroxylase), CYP11B1 (11b-hydroxylase), CYP17A (17ahydroxylase).
Adrenal histology: Hyperplasia of the adrenal cortex and disorganized architecture of cortices and medullae.
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.
Enzyme deficiency: 21-hydroxylase (90%), 11b-hydroxylase deficiency (5%) and 17a-hydroxylase deficiency (5%).
Consanguinity and family history are risk factors.
Summarise the epidemiology for congenital adrenal hyperplasia.
1/10,000 (21-hydroxylase deficiency)
1/100,000 (11b-hydroxylase and 17a-hydroxylase deficiency)
What are the signs and symptoms of male classic salt-wasting congenital adrenal hyperplasia?
Salt-losing crisis; occurs with severe 21-hydroxylase deficiency. Males present <1/12 old.
Symptoms: failure to thrive, recurrent vomiting, sweating, dehydration, hyponatremia, hyperkalemia, hypotension and coma rapidly followed by death.
What are the signs and symptoms of male classic viriliser congenital adrenal hyperplasia?
Early development of secondary sexual characteristics (pubic hair and phallic enlargement) and accelerated growth and increased skeletal maturation.
What are the signs and symptoms of female classic salt-wasting congenital adrenal hyperplasia?
Ambiguous genitalia; clitoromegaly
Fused labia at birth.
What are the signs and symptoms of female classic viriliser congenital adrenal hyperplasia?
Virilisation: acne, hirsutism, accelerated growth, increased skeletal maturation.
What are the signs and symptoms of 17a-hydroxylase deficiency congenital adrenal hyperplasia?
Increased 11-deoxycorticosterone (mineralocorticoid), decreased androgens.
- Males present with ambiguous or female genitalia.
- Females present with absence of secondary sexual characteristics at puberty.
What are the signs and symptoms of 11b-hydroxylase deficiency congenital adrenal hyperplasia?
May present as a salt-losing crisis in a neonate.
When older, develop hypertension as mineralocorticoid (deoxycorticosterone) sensitivity increased with age.
What are the investigations for congenital adrenal hyperplasia?
Bloods: 17-hydroxyprogesterone (Increased in 21-hydroxylase deficiency and 11b-hydroxylase deficiency), testosterone, increased basal ACTH, LH, FSH, U&E.
ACTH stimulation test: Inappropriately elevated 17-hydroxyprogesterone levels after IM ACTH.
Pelvic ultrasound: Presence of uterus/polycystic ovary syndrome/renal anomaly.
Karyotyping and molecular genetics: Mutation location and chromosomal sex.
What is the management plan for acute salt-losing crisis?
IV 0.9% NaCl (20 ml/kg) over first hour and repeated as necessary, dextrose and 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
- Mineralocorticoid
- 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 and 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.
