Congenital adrenal hyperplasia (CAH) is a group of inherited disorders of adrenal steroid synthesis, most commonly caused by 21-hydroxylase deficiency. It can present with virilization, salt wasting, dehydration, hypotension, or precocious androgen effects, depending on the enzyme defect and severity. For exam questions, the key is to recognize the clinical pattern, blood pressure, electrolytes, and characteristic hormone abnormality to identify the enzyme defect quickly.
21-Hydroxylase deficiency
Key concept
Congenital adrenal hyperplasia (CAH) is a group of autosomal-recessive disorders of adrenal steroid synthesis. Impaired cortisol synthesis causes ↑ ACTH, adrenal hyperplasia and accumulation of steroid precursors. The clinical picture depends on the enzyme affected and the severity of the defect. 21-hydroxylase deficiency accounts for >90% of CAH cases and is the most important form for pediatric exams.
21-Hydroxylase deficiency — most important
21-hydroxylase deficiency → ↓ cortisol + ↑ adrenal androgens
In the salt-wasting form, there is also significant ↓ aldosterone, resulting in:
- Hyponatremia
- Hyperkalemia
- Dehydration
- Hypotension
- Adrenal crisis
The characteristic biochemical marker is markedly elevated 17-hydroxyprogesterone (17-OHP). Newborn screening for 21-hydroxylase deficiency uses 17-OHP.
Clinical presentations
46,XX newborn:
- Virilized/ambiguous external genitalia
- May have clitoromegaly and labioscrotal fusion
46,XY newborn:
- External genitalia may appear normal at birth
- Salt-wasting crisis may subsequently reveal the diagnosis
Later childhood/adolescence:
- Premature adrenarche/pubarche
- Rapid growth
- Advanced bone age
- Acne, hirsutism or menstrual irregularity in females
Three phenotypes of 21-hydroxylase deficiency
Salt-wasting classic CAH
→ severe enzyme deficiency
→ ↓ cortisol + ↓ aldosterone + ↑ androgens
→ salt wasting and adrenal crisis
Simple-virilizing classic CAH
→ ↓ cortisol + ↑ androgens
→ sufficient mineralocorticoid activity to avoid clinically significant salt wasting
Non-classic CAH
→ milder enzyme deficiency
→ later androgen excess
→ usually no salt-wasting crisis
→ may present with premature adrenarche, acne, hirsutism or menstrual irregularity.
In a boy with non-classic CAH
Because residual 21-hydroxylase activity is present, aldosterone production is generally sufficient, so he does not present with the classic salt-wasting crisis. Instead, the excess adrenal androgens may cause:
- Premature pubic/axillary hair
- Rapid linear growth
- Advanced bone age
- Early penile enlargement
- Early beard/virilization
- Precocious puberty or precocious pubertal development
Other enzyme defects
Other enzyme defects — very high yield
| Enzyme defect | Androgens | Mineralocorticoid effect | BP | Classic clue |
|---|---|---|---|---|
| 21-hydroxylase | ↑ | ↓ | ↓ | Virilization + salt wasting |
| 11β-hydroxylase | ↑ | ↑ DOC | ↑ | Virilization + hypertension |
| 17α-hydroxylase | ↓ | ↑ DOC | ↑ | Hypertension + low sex steroids |
Memory aid
21 → salt loss + androgens ↑
11 → hypertension + androgens ↑
17 → hypertension + androgens ↓
Approach a CAH MCQ
How to Approach a CAH MCQ
1. Look for androgen excess
Ambiguous genitalia/virilization in a newborn girl → think CAH, particularly 21-hydroxylase deficiency.
2. Look for salt wasting
Vomiting + dehydration + hypotension + hyponatremia + hyperkalemia
→ strongly suggests salt-wasting 21-hydroxylase deficiency.
3. Check the blood pressure
Hypotension/salt wasting → 21-hydroxylase
Hypertension + virilization → 11β-hydroxylase
Hypertension + undervirilization/sexual infantilism → 17α-hydroxylase
4. Look at the hormone
↑ 17-OHP → 21-hydroxylase deficiency
For symptomatic patients beyond infancy, an early-morning 17-OHP is recommended. If the result is borderline, an ACTH (cosyntropin) stimulation test with a broader adrenal steroid profile can help distinguish 21-hydroxylase deficiency from other enzyme defects.
5. If the question asks about treatment
Classic CAH → glucocorticoid replacement with hydrocortisone.
Salt-wasting disease additionally requires mineralocorticoid replacement (fludrocortisone) and, particularly in infancy, sodium supplementation. During adrenal crisis, treatment requires urgent parenteral hydrocortisone and appropriate fluid/electrolyte and glucose management
Very useful MCQ pattern
Boy aged 6–8 years + pubic hair + penile enlargement + rapid growth + advanced bone age + no salt wasting → think CAH, particularly 21-hydroxylase deficiency.
🧠 10-Second CAH Exam Rule
Quick Approach
Virilization + salt wasting + hypotension → 21-hydroxylase deficiency
Virilization + hypertension → 11β-hydroxylase deficiency
Hypertension + low sex steroids → 17α-hydroxylase deficiency
↑ 17-OHP → 21-hydroxylase deficiency
