4. Disorders of Sex Development: a three‑axis approach

First principle: assess three axes independently

Do not ask "is this a boy or a girl?" Ask three separable questions:

Worked reasoning: 21‑hydroxylase CAH

The commonest DSD in a 46,XX infant is congenital adrenal hyperplasia:

Red flags 🚩

• Salt‑wasting CAH (aldosterone deficiency) causes hyponatraemia, hyperkalaemia and hypovolaemic collapse in the first weeks of life — a genuine neonatal emergency. An "ambiguous genitalia" baby is a metabolic time‑bomb until CAH is excluded.

Discriminators

• High 17‑OHP → CAH. XY + female external genitalia + absent uterus → CAIS. XY + uterus present + streak gonads → Swyer.

Pitfalls

• Assigning sex or rushing surgery before the karyotype, biochemistry and multidisciplinary assessment. This is an endocrine and ethical decision, not a snap anatomical one.
• Missing the salt‑wasting crisis while focused on the genitalia.

Pearls

• 🎯 The CAH chain — enzyme block → ↓cortisol → ↑ACTH → ↑adrenal androgens — is a reusable template for endocrine feedback.
• 🩺 Check electrolytes urgently in any virilised neonate.

Next → With the body built, the engine starts — the HPO axis as a control system (Concept 5).