Congenital Adrenal Hyperplasia in Females
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Direct answer
Congenital adrenal hyperplasia in females is most often caused by 21-hydroxylase deficiency, which diverts cortisol precursors into androgen synthesis and virilises the external genitalia of a 46,XX fetus. Affected girls may have ambiguous genitalia at birth, and the classic salt-wasting form can cause life-threatening hyponatraemia and hypotension in the first weeks. Diagnosis rests on raised serum 17-hydroxyprogesterone, and lifelong glucocorticoid replacement, with mineralocorticoid cover where needed, prevents adrenal crisis.
What you must remember
- Commonest cause: 21-hydroxylase deficiency due to CYP21A2 mutations accounts for about 90 to 95 per cent of congenital adrenal hyperplasia cases.
- Ambiguous genitalia: Prader staging grades virilisation from I to V, and 46,XX girls show clitoromegaly, labial fusion and sometimes a urogenital sinus.
- Salt-wasting form: aldosterone deficiency causes hyponatraemia, hyperkalaemia and dehydration in the first weeks, which is a neonatal emergency.
- Simple virilising and non-classic forms: the simple virilising form lacks salt wasting, while the non-classic form presents later with hirsutism, oligomenorrhoea or early pubarche.
- Diagnosis: serum 17-hydroxyprogesterone measured in the morning in newborns and in the early follicular phase in adults, with an ACTH stimulation test or genetic analysis confirming the diagnosis.
- Treatment: lifelong hydrocortisone in divided doses, fludrocortisone for salt wasting, stress-dose cover during illness and surgery, and emergency parenteral hydrocortisone at home or in hospital.
A stepwise approach to the newborn with ambiguous genitalia
A newborn girl has clitoromegaly, fused labia and a urogenital sinus, and by day 10 she vomits and gains weight poorly. These features point towards the salt-wasting form of congenital adrenal hyperplasia, which must be treated before results return. The steps below show the usual order of management.
- Suspect early: Ambiguous genitalia in a 46,XX newborn with raised 17-hydroxyprogesterone points to congenital adrenal hyperplasia and needs urgent specialist evaluation.
- Check electrolytes: Hyponatraemia, hyperkalaemia, hypoglycaemia and hypotension signal the salt-wasting form and call for immediate treatment.
- Confirm the diagnosis: A 46,XX karyotype, raised 17-hydroxyprogesterone and elevated androstenedione, with CYP21A2 genetic testing, confirm the defect.
- Start replacement: Hydrocortisone is started promptly, with fludrocortisone added for salt wasting, and treatment must not be delayed for test results.
- Teach stress dosing: Parents and the older child learn when to give emergency injectable hydrocortisone during vomiting, fever or surgery.
- Plan surgery and follow-up: Paediatric surgery and endocrinology coordinate the timing of feminising genitoplasty, with growth and bone age monitored throughout.
Where the exam tries to catch you
Examiners test whether you can recognise the disorder in a newborn and avoid the pitfalls of long-term steroid management.
- Trap: Attribute ambiguous genitalia in a 46,XX newborn to a testicular disorder. Correct: In 46,XX ambiguous genitalia the gonads are ovaries, and congenital adrenal hyperplasia is the commonest cause, so testicular disorders belong to 46,XY.
- Trap: Stop glucocorticoids once androgen levels fall. Correct: The adrenal enzyme defect is lifelong, so glucocorticoids must continue, and stopping them risks adrenal crisis.
- Trap: Give prenatal dexamethasone routinely to every affected pregnancy. Correct: Prenatal treatment is controversial and reserved for specialist centres because of maternal and fetal risks.
- Trap: Miss late-onset congenital adrenal hyperplasia in a hirsute adolescent. Correct: The non-classic form mimics polycystic ovary syndrome, so 17-hydroxyprogesterone is checked in the early follicular phase before PCOS is accepted.
Frequently asked questions
Which enzyme defect causes most cases of congenital adrenal hyperplasia in females?
21-hydroxylase deficiency, caused by CYP21A2 mutations, causes about 90 to 95 per cent of congenital adrenal hyperplasia cases. The block shunts steroid precursors towards androgens, which virilise the external genitalia of a 46,XX girl.
What is the best screening test for congenital adrenal hyperplasia?
Serum 17-hydroxyprogesterone is the key screening test for congenital adrenal hyperplasia due to 21-hydroxylase deficiency, drawn in the early morning in newborns and in the early follicular phase in women. A raised value supports the diagnosis, which is then confirmed by ACTH stimulation testing or genetic analysis.
Why is hydrocortisone given in congenital adrenal hyperplasia?
Hydrocortisone replaces cortisol and suppresses the excess ACTH drive that causes adrenal overproduction of androgens in congenital adrenal hyperplasia. Replacement must be lifelong and increased during illness, fever or surgery to prevent crisis.
What is the danger of congenital adrenal hyperplasia in the newborn period?
The salt-wasting form of congenital adrenal hyperplasia causes hyponatraemia, hyperkalaemia and dehydration, which can lead to adrenal crisis within the first weeks of life. Prompt electrolyte checks and immediate hydrocortisone and fludrocortisone prevent death in the affected newborn.