Congenital Adrenal Hyperplasia
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Direct answer
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive defects of adrenal steroidogenesis; 21-hydroxylase deficiency causes about nine in ten cases, blocking cortisol and aldosterone synthesis so that excess ACTH drives the gland and shunts precursors into androgens. A newborn girl presents with ambiguous genitalia — clitoromegaly and labial fusion — while a boy looks normal at birth and returns in the second or third week with a salt-wasting crisis of vomiting, dehydration, hyponatraemia, hyperkalaemia and hypoglycaemia. Diagnosis rests on a raised 17-hydroxyprogesterone, and treatment is lifelong glucocorticoid with mineralocorticoid and salt for salt-wasters.
What you must remember
- 21-hydroxylase deficiency: the large majority; low cortisol and aldosterone with high 17-hydroxyprogesterone (the diagnostic marker) and excess androgens; presents as salt-wasting, simple virilising or non-classic disease.
- Salt-wasting crisis: at one to three weeks with poor weight gain, vomiting, dehydration, hyponatraemia, hyperkalaemia, hypoglycaemia and acidosis — an emergency needing intravenous saline, glucose and hydrocortisone.
- Genital findings: virilised genitalia in affected girls; boys appear normal at birth and later show isosexual precocity with pigmentation and phallic growth.
- Other enzyme defects: 11-beta-hydroxylase — virilisation with hypertension; 3-beta-hydroxysteroid dehydrogenase — salt-wasting with undervirilised boys; 17-alpha-hydroxylase — hypertension, hypokalaemia and pubertal failure.
- Workup of ambiguous genitalia: karyotype, pelvic and adrenal ultrasound, electrolytes, glucose and 17-hydroxyprogesterone, with ACTH stimulation if baseline is equivocal.
- Treatment: hydrocortisone in physiological doses (two- to threefold during illness), fludrocortisone with salt for salt-wasters, monitoring electrolytes, renin, 17-OHP, growth and blood pressure.
- Screening: newborn 17-hydroxyprogesterone screening exists in many countries but is not yet universal in India — worth noting for programme questions.
Common confusion
The classic confusion is 21-hydroxylase versus 11-beta-hydroxylase deficiency: both virilise, but only 11-beta causes hypertension from mineralocorticoid precursor accumulation, while 21-hydroxylase salt-wasters become hypotensive. The second trap is the "normal-looking boy": girls come to diagnosis early through ambiguous genitalia, whereas boys present only at the salt-wasting crisis — any male infant with unexplained vomiting and hyponatraemic hyperkalaemia needs urgent 17-hydroxyprogesterone. Distinguish also from androgen insensitivity and 5-alpha-reductase deficiency, which undervirilise boys rather than virilise girls.
Exam-focused takeaway
NEET-PG leans on four anchors: the enzyme (21-hydroxylase, commonest), the marker (17-hydroxyprogesterone), the crisis (hyponatraemia with hyperkalaemia and hypoglycaemia in a fortnight-old boy) and the treatment (hydrocortisone plus fludrocortisone with stress dosing). Expect vignettes of ambiguous genitalia in a 46,XX newborn — virilising CAH — and laboratory interpretation pairing low cortisol with high ACTH, high renin and high androgens. The enzyme ladder with blood pressure as the discriminator is a repeated one-liner set, and autosomal recessive inheritance with one-in-four recurrence risk feeds counselling stems.
Frequently asked questions
Which enzyme deficiency is commonest?
21-hydroxylase deficiency, causing about 90 per cent of cases; it blocks cortisol and aldosterone synthesis and diverts precursors into androgens.
Why are girls virilised but boys look normal at birth?
Excess adrenal androgens virilise the developing female external genitalia in utero; male genitalia are already virilised, so nothing changes visibly until later precocity.
What is the diagnostic marker?
A markedly raised serum 17-hydroxyprogesterone, confirmed on the baseline sample or after ACTH stimulation in borderline cases.
How is a salt-wasting crisis managed?
Intravenous normal saline with dextrose, hydrocortisone and management of hyperkalaemia, with monitoring for shock, arrhythmia and hypoglycaemia.
How does 11-beta-hydroxylase deficiency differ?
It also virilises, but accumulating 11-deoxycorticosterone produces hypertension and hypokalaemia rather than salt-wasting — the key discriminator.
What maintenance treatment is needed?
Lifelong hydrocortisone (with fludrocortisone and salt in salt-wasting forms), increased during illness and monitored clinically and biochemically to avoid over- and under-treatment.