Congenital Adrenal hyperplasia
Related Subjects:
|Adrenal Physiology
|Addisons Disease
|Phaeochromocytoma
|Adrenal Adenomas
|Adrenal Cancer
|Cushing Syndrome
|Cushing Disease
|Congenital Adrenal hyperplasia
|Primary hyperaldosteronism (Conn's syndrome)
|ACTH
|McCune Albright syndrome
⚡ Congenital Adrenal Hyperplasia (CAH) is an inherited enzyme defect in steroid hormone synthesis.
Failure to produce cortisol (and sometimes aldosterone) → loss of negative feedback → ↑ ACTH → adrenal hyperplasia + overproduction of other steroids (mainly androgens).
📖 About
- First described in 1865 by the Neapolitan anatomist De Crecchio.
- Autosomal recessive disorder.
- Loss of cortisol production causes overdrive of ACTH and excess adrenal steroids.
- Results in a mixture of deficiency (cortisol ± aldosterone) and excess (androgens, mineralocorticoid intermediates).
🧬 Aetiology
- Most commonly due to mutations in CYP21A2 (21-hydroxylase) gene (~95%).
- Leads to adrenal crisis + androgen excess.
- Other rarer enzyme defects include CYP11B1 (11β-hydroxylase) and CYP17 (17-hydroxylase).
⚧ Virilisation
- Females: ambiguous genitalia at birth (enlarged clitoris, labioscrotal fusion); precocious pubic hair.
- Males: enlarged penis, small testes, early puberty, acne, deep voice; precocious pubic hair.
🔎 Clinical Subtypes
- 21-hydroxylase deficiency (CYP21A2) 🧩
- 95% of cases.
- Virilisation in females; early puberty in boys.
- Salt-wasting crisis in ~70% (hyponatraemia, hyperkalaemia, hypoglycaemia, hypotension).
- Investigations: ↑ 17-hydroxyprogesterone, ↑ testosterone/androstenedione, ↓ cortisol, ↓ aldosterone.
- 11β-hydroxylase deficiency (CYP11B1) 💉
- ~5% of cases.
- Virilisation in females; ambiguous genitalia at birth.
- Hypertension + hypokalaemia due to 11-deoxycorticosterone (DOC) accumulation.
- Investigations: ↓ cortisol, ↑ 11-deoxycortisol, ↑ androgens.
- 17-hydroxylase deficiency (CYP17) 🔬
- Very rare.
- Non-virilising; intersex in XY males, phenotypically female external genitalia.
- Hypertension + hypokalaemia (↑ DOC), low sex steroids.
- Investigations: ↓ cortisol, ↓ 17-OHP, ↓ testosterone, ↓ DHEA.
🩺 Management
- Glucocorticoids (hydrocortisone in children, dexamethasone/prednisone in adults) → suppress CRF & ACTH.
- Mineralocorticoid replacement (fludrocortisone) in salt-wasting forms.
- Surgery may be needed for genital reconstruction in females with ambiguous genitalia.
🚨 Adrenocortical Crisis
- IV hydrocortisone (stress dose).
- IV normal saline (resuscitation).
- IV glucose if hypoglycaemic.
- Fludrocortisone usually not required acutely (except in salt-wasting form).
