Congenital adrenal hyperplasia and adrenal hormone disorders compared
How an inherited block in cortisol synthesis, most often 21-hydroxylase deficiency, lets ACTH enlarge both adrenals and divert precursors into androgens, causing virilisation and salt-wasting, and how every adrenal syndrome compares.
By the end, you can
- Trace the adrenal steroid pathway from cholesterol to aldosterone, cortisol and androgens, and explain why each zone makes its own hormone.
- Explain how 21-hydroxylase deficiency raises ACTH, enlarges both adrenals and diverts 17-hydroxyprogesterone into androgens.
- Relate the salt-wasting, simple virilising and non-classic forms to residual enzyme activity and to their presentations.
- Explain why 11β-hydroxylase deficiency causes hypertension instead of salt-wasting, and place every adrenal excess and deficiency syndrome by hormone, ACTH and renin.
- Recognise the morphology, key tests and differentials of CAH, and explain how glucocorticoid and mineralocorticoid replacement act on its mechanism.
What it is
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive defects in an enzyme of adrenal steroid synthesis that impair cortisol production. Low cortisol raises ACTH, which enlarges both adrenal glands. In the commonest form, 21-hydroxylase deficiency, the blocked precursors are diverted into androgens and, in severe cases, aldosterone is also lacking.
4 types to tell apart
- Classic salt-wasting
- Almost no 21-hydroxylase activity: cortisol and aldosterone are both very low, causing virilisation of 46,XX babies and a salt-wasting crisis in the first weeks of life.
- Classic simple virilising
- A little enzyme activity, enough to make aldosterone: virilisation of 46,XX babies, and early androgen effects in childhood in both sexes, without a salt-wasting crisis.
- Non-classic
- Substantial residual activity: cortisol and aldosterone are normal, and mild androgen excess appears in later childhood or adulthood.
- 11β-hydroxylase deficiency
- A block one step later: androgen excess as in 21-hydroxylase deficiency, but the build-up of deoxycorticosterone retains salt and raises blood pressure.
Normal function
One cholesterol, three steroid families
The adrenal cortex builds all its hormones from cholesterol, taken up from LDL in the blood or made in the cell, and stored as lipid droplets. The first, rate-limiting step moves cholesterol into the mitochondria (helped by the StAR protein) and cuts off its side chain to make pregnenolone. A short series of enzymes, most of them cytochrome P450 (CYP) enzymes, then adds or rearranges chemical groups to make each hormone.
Which hormone a cell makes depends on which enzymes it carries. The lacks 17α-hydroxylase but has aldosterone synthase, so it turns progesterone into aldosterone. The has 17α-hydroxylase: it makes 17-hydroxyprogesterone, which 21-hydroxylase turns into 11-deoxycortisol and 11β-hydroxylase into cortisol. The uses the 17,20-lyase activity of the same 17α-hydroxylase enzyme to make the androgens DHEA and androstenedione, a branch that needs neither 21- nor 11β-hydroxylase.
ACTH from the pituitary drives the fasciculata and reticularis: it speeds the first step and keeps both zones large, and cortisol feeds back to hold ACTH down. Aldosterone is controlled separately, by angiotensin II and plasma potassium. So a defect in cortisol synthesis changes ACTH, while a lack of aldosterone shows up as a high renin.
| Feature | Glomerulosa: aldosterone | Fasciculata: cortisol | Reticularis: androgens |
|---|---|---|---|
| From pregnenolone | Progesterone | 17-hydroxyprogesterone (17α-hydroxylase) | 17-hydroxypregnenolone (17α-hydroxylase) |
| 21-hydroxylase step | Progesterone → 11-deoxycorticosterone (DOC) | 17-OHP → 11-deoxycortisol | Not needed |
| 11β-hydroxylation | DOC → corticosterone (by aldosterone synthase) | 11-deoxycortisol → cortisol (11β-hydroxylase) | Not needed |
| Final product | Aldosterone (aldosterone synthase) | Cortisol | DHEA and androstenedione (17,20-lyase) |
| Main control | Angiotensin II and potassium | ACTH | ACTH |
| If 21-hydroxylase fails | Aldosterone falls in severe forms | Cortisol falls; 17-OHP builds up | Receives the diverted precursors: androgens rise |
Simplified. All zones share the first step from cholesterol to pregnenolone (side-chain cleavage, helped by StAR). Testosterone is completed mainly in the gonads and peripheral tissues.
Underlying change · Step 1 of 5
A missing enzyme blocks cortisol synthesis
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Underlying change · Step 2 of 5
ACTH enlarges the cortex and diverts precursors to androgens
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Androgen excess before birth and through childhood
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It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Salt-wasting: when aldosterone fails too
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
11β-hydroxylase deficiency, and all adrenal syndromes compared
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .