Summary

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting adrenal steroidogenesis. The vast majority (~95%) are caused by 21-hydroxylase deficiency (21-OHD), which impairs cortisol and aldosterone synthesis while shunting precursors towards androgen production. The clinical spectrum ranges from the severe "classic" forms (salt-wasting and simple virilising) to the milder "non-classic" form. Classic salt-wasting CAH presents in the first 1-2 weeks of life with life-threatening adrenal crisis (hyponatraemia, hyperkalaemia, shock) and virilisation of female genitalia. Early diagnosis through newborn screening programmes and prompt treatment with glucocorticoid and mineralocorticoid replacement is life-saving. Non-classic CAH presents later with signs of androgen excess (hirsutism, acne, oligomenorrhoea).

Key Facts

• Inheritance: Autosomal recessive; carrier frequency ~1:50 in general population
• Enzyme defect: 21-hydroxylase (CYP21A2) — 95% of CAH
• Pathophysiology: Low cortisol → High ACTH → Adrenal hyperplasia → Excess androgens
• Classic salt-wasting (~75%): Aldosterone + cortisol deficiency; adrenal crisis at 1-2 weeks
• Classic simple virilising (~25%): Cortisol deficiency; excess androgens; no salt-wasting
• Non-classic (late-onset): Mild; androgen excess symptoms; often diagnosed in adolescence/adulthood
• Diagnosis: Elevated 17-hydroxyprogesterone (17-OHP) — blood spot screening
• Treatment: Hydrocortisone + Fludrocortisone (salt-wasters); stress dosing during illness
• Virilisation: Female neonates have ambiguous genitalia (clitoromegaly, labial fusion); males may be undetected until crisis

Clinical Pearls

"A Sick Neonate at 1-2 Weeks = Think CAH": Classic salt-wasting CAH presents around day 7-14 with poor feeding, vomiting, lethargy, and shock. Hyponatraemia + hyperkalaemia should trigger urgent investigation.

"Female with Ambiguous Genitalia = CAH Until Proven Otherwise": Virilised female genitalia (clitoromegaly, fused labia but absent gonads) is the hallmark presentation. The baby is 46,XX but appears masculinised.

"17-OHP Is the Diagnostic Test": Elevated 17-hydroxyprogesterone (17-OHP) confirms 21-hydroxylase deficiency. Newborn screening picks up most cases in screened populations.

"Stress Dosing Saves Lives": Patients with CAH need doubled or tripled hydrocortisone doses during illness/stress. Parents must be educated on emergency management and given IM hydrocortisone for emergencies.

"Boys Present Later or Not at All": Male infants may not show virilisation (they're already male) and can present later with precocious puberty or in life-threatening crisis. Salt-wasting crisis is often the first sign.

Why This Matters Clinically

CAH is a medical emergency in neonates. Undiagnosed salt-wasting CAH is fatal. Early recognition, newborn screening, and lifelong hormone replacement prevent adrenal crises and optimise growth and development. All clinicians should be able to recognise and initiate emergency treatment for adrenal crisis.[1,2]

Neonatal Examination

General:

• Lethargy or irritability
• Dehydration (skin turgor, sunken fontanelle, dry mucous membranes)
• Hyperpigmentation (nipples, genitalia)

Genitalia — Female (46,XX):

Key Point: Gonads are NOT palpable in virilised 46,XX females (ovaries are intra-abdominal). In a "male" with undescended testes and hypospadias, consider CAH.

Genitalia — Male:

• Usually normal at birth
• May have scrotal hyperpigmentation
• May present later with precocious puberty

With Treatment

Without Treatment

Key Guidelines

Key Evidence

Newborn Screening Impact

• Introduction of newborn screening has virtually eliminated deaths from salt-wasting CAH in screened populations
• Early detection allows treatment before crisis

What is Congenital Adrenal Hyperplasia (CAH)?

CAH is a genetic condition affecting the adrenal glands — small glands above the kidneys that make important hormones. In CAH, the adrenal glands can't make enough of the hormone cortisol, and sometimes aldosterone. This causes the body to make too many male hormones (androgens).

How does it affect babies?

Salt-wasting CAH (most common form):

• Babies can become very unwell in the first 1-2 weeks with vomiting, poor feeding, and dehydration
• This is a medical emergency and needs urgent treatment

Genital differences:

• Baby girls may have genitals that look different (somewhere between male and female) because of too many male hormones
• Baby boys often look normal but can become very sick

How is it treated?

• Hormone replacement: Daily tablets (hydrocortisone to replace cortisol; fludrocortisone to replace aldosterone)
• Salt supplements: Especially for babies
• Sick day rules: Extra doses when unwell
• Emergency injection: Parents are trained to give an injection if the child is vomiting or very unwell

Will my child lead a normal life?

With proper treatment and monitoring, children with CAH grow up to lead healthy, active lives. They need to take medication every day and carry emergency medication.

High-Yield Exam Topics

Sample Viva Questions

Q1: A 10-day-old baby presents with poor feeding, vomiting, and lethargy. Sodium is 120 mmol/L and potassium is 7.2 mmol/L. What is your differential and management?

Model Answer: This presentation is highly suspicious for salt-wasting congenital adrenal hyperplasia (21-hydroxylase deficiency). The combination of hyponatraemia, hyperkalaemia, and shock in a neonate at 1-2 weeks is classic. Immediate management: IV access, 0.9% saline bolus 20 mL/kg, IV hydrocortisone 25 mg stat, treat hyperkalaemia (calcium gluconate if ECG changes, insulin-dextrose), check glucose. Investigations: 17-OHP (will be markedly elevated), cortisol, ACTH, renin, aldosterone, blood gas, glucose. Examine genitalia (virilised female?). This is a medical emergency — do not delay treatment waiting for results. Confirmatory: Genetic testing CYP21A2.

Q2: How do you differentiate salt-wasting from simple virilising CAH?

Model Answer: Both forms have cortisol deficiency and androgen excess. The difference is aldosterone:

• Salt-wasting (~75%): Also has aldosterone deficiency; presents with adrenal crisis (hyponatraemia, hyperkalaemia, shock) in first 1-2 weeks; requires fludrocortisone replacement
• Simple virilising (~25%): Aldosterone production is preserved; no salt-wasting crisis; presents with virilisation at birth (females) or precocious puberty (males) Clinically, check plasma renin and aldosterone. Salt-wasters have elevated renin and low aldosterone.

Q3: What are the sick-day rules for a child with CAH?

Model Answer: During illness or stress, cortisol requirements increase. Sick-day rules:

• Minor illness (fever, cold): Double the hydrocortisone dose
• Moderate illness (gastroenteritis, high fever): Triple the hydrocortisone dose
• Vomiting or unable to take oral medication: IM hydrocortisone immediately (25 mg <1 yr; 50 mg 1-5 yrs; 100 mg >6 yrs/adult) and seek medical attention
• Surgery/major procedure: IV hydrocortisone cover perioperatively

Parents must be trained to give IM injections and have emergency hydrocortisone at home. Child should wear a MedicAlert bracelet.

Common Exam Errors

Last Reviewed: 2025-12-24 | MedVellum Editorial Team

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.