Congenital adrenal hyperplasia
- Mechanism
In congenital adrenal hyperplasia, a missing enzyme blocks cortisol production. The adrenals grow and make extra male hormones instead.
What it is
Adrenogenital syndromes are disorders of androgen excess from the adrenal cortex, caused by tumours or, most often, by congenital adrenal hyperplasia (CAH). CAH is a group of autosomal recessive defects of cortisol synthesis. Low cortisol raises ACTH, which drives bilateral hyperplasia and pushes precursors into the androgen pathway. 21-hydroxylase deficiency causes the great majority of cases and is detected by newborn screening in many countries.
Structure
- Both adrenals are enlarged, sometimes many times normal, with a thick brown cortex (lipid-depleted compact cells).
- Pituitary: corticotroph hyperplasia.
- Adrenal rest tumours of the testis can form from ACTH-driven ectopic adrenal tissue.
Step by step
- An enzyme defect blocks the cortisol pathway.
- Low cortisol removes negative feedback: ACTH rises.
- ACTH stimulates bilateral cortical hyperplasia.
- Precursors before the block accumulate and are shunted into the androgen (or mineralocorticoid) pathway.
- Effects depend on the enzyme: androgen excess, salt loss or salt retention.
Three enzyme defects compared
| Enzyme | Mineralocorticoid | Androgens | Blood pressure | Clue |
|---|---|---|---|---|
| 21-hydroxylase | Low (salt wasting in classic form) | High | Low | High 17-hydroxyprogesterone; virilised girls |
| 11-beta-hydroxylase | 11-deoxycorticosterone high | High | High | Virilisation with hypertension |
| 17-alpha-hydroxylase | 11-deoxycorticosterone high | Low | High | Hypokalaemia; no puberty; undervirilised boys |
Clinical notes
- Salt-wasting crisis in a newborn can be fatal if missed; boys may look normal at birth.
- Androgen excess accelerates growth but closes growth plates early: short adult stature.
- Other adrenogenital causes: androgen-secreting adrenocortical carcinoma (usually) or adenoma.
Test yourself
Think of the answer, then tap the question to see it.
Why are the adrenals enlarged in congenital adrenal hyperplasia?
Low cortisol removes feedback on the pituitary; high ACTH drives bilateral cortical hyperplasia.
Which CAH form causes virilisation and hypertension?
11-beta-hydroxylase deficiency, through excess 11-deoxycorticosterone and androgens.
Which steroid is high in 21-hydroxylase deficiency and used for screening?
17-hydroxyprogesterone.
Elsewhere in DurgiPedia
- Differences of sex development: CAH, AIS and 5α-reductase
- Adrenal cortisol synthesis
- 21-Hydroxylase (CYP21A2)
- 11β-Hydroxylase (CYP11B1)
- 17α-Hydroxylase/17,20-lyase (CYP17A1)
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Congenital adrenal hyperplasia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); 21-hydroxylase deficiency (MedlinePlus, US National Library of Medicine, 2025); Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.