Congenital Adrenal Hyperplasia (CAH)
Summary
Congenital Adrenal Hyperplasia (CAH) describes a group of autosomal recessive disorders where an enzymatic defect blocks cortisol synthesis in the adrenal cortex. The pituitary responds to low cortisol by pumping out ACTH, which causes adrenal hyperplasia and drives the accumulation of precursor hormones into the androgen pathway.
- 21-Hydroxylase Deficiency accounts for >95% of cases.
- It is the most common cause of ambiguous genitalia in females and salt-wasting shock in neonates. [1,2]
Clinical Pearls
The "Silent" Male: Female infants are often diagnosed at birth due to ambiguous genitalia (virilisation). Male infants have normal genitalia and are often sent home, only to present at Day 10-14 in cardiovascular collapse (Salt-Wasting Crisis). Any male infant with "sepsis-like" shock and hyperkalaemia has CAH until proven otherwise.
Pyloric Stenosis vs CAH: Both present with a vomiting male infant at 2-3 weeks.
- Pyloric Stenosis: Hypochloraemic Alkalosis.
- CAH: Hyperkalaemic Acidosis. Check the U&Es!
Precocious Puberty: In "Non-Classic" or poorly controlled CAH, the excess androgens cause rapid growth (tall child) and early pubic hair/penile growth. However, the epiphyses fuse early, resulting in a short adult.
Demographics
- Incidence: 1 in 15,000 live births.
- Genetics: Autosomal Recessive. Carrier rate 1 in 60.
Phenotypes
- Classic Salt-Wasting (75%): Complete enzyme absence. Zero Cortisol, Zero Aldosterone. Crisis in neonatal period.
- Classic Simple Virilising (25%): 1-2% enzyme activity. Enough Aldosterone to prevent salt crisis, but not enough Cortisol. Virilisation present.
- Non-Classic (Late Onset): 20-50% activity. Present in childhood/adolescence with hirsutism/oligomenorrhoea.
The Steroid Pathway
Adrenal cortex makes three classes of hormones from Cholesterol:
- Mineralocorticoids (Aldosterone): Requires 21-OH enzyme.
- Glucocorticoids (Cortisol): Requires 21-OH enzyme.
- Androgens (Testosterone): Does NOT require 21-OH.
The 21-Hydroxylase Block
- Block: Precursors (17-OH Progesterone) cannot become Cortisol/Aldosterone.
- Shunt: They accumulate and spill over into the Androgen pathway.
- Result:
- Low Cortisol: Hypoglycaemia, poor stress response.
- Low Aldosterone: Salt loss (Low Na), Potassium retention (High K), Hypovolaemia.
- High Androgens: Virilisation.
Neonatal Female
Neonatal Male
Older Child (Non-Classic)
- Genitalia: Prader staging for virilisation. Palpate for testes (If clitoromegaly + NO testes = likely CAH female. If testes present = likely male or androgen insensitivity).
- Pigmentation: Hyperpigmentation of nipples/scrotum (High ACTH).
- BP: Hypotension (in salt wasters). Hypertension (in rare 11-beta-hydroxylase deficiency).
Biochemistry
- 17-Hydroxyprogesterone (17-OHP): The hallmark. Markedly elevated (>300 nmol/L).
- U&Es: Hyponatraemia (Na less than 130), Hyperkalaemia (K >6.0), Metabolic Acidosis.
- Glucose: Low.
Genetics
- Karyotype: Essential for ambiguous genitalia (e.g., 46 XX).
- Mutaion Analysis: CYP21A2 gene.
Stimulation Test
- Short Synacthen Test: In non-classic cases. Exaggerated 17-OHP response to ACTH.
Management Algorithm
SUSPECTED CAH
(Ambiguous Genitalia / Shock)
↓
STABILISE (ABCDE)
- 20ml/kg 0.9% Saline bolus
- Check Glucose (Give Dextrose)
- Treat Hyperkalemia
↓
CONFIRM DIAGNOSIS
(High 17-OHP, U&Es)
↓
LONG TERM THERAPY
┌─────────┴─────────┐
GLUCOCORTICOID MINERALOCORTICOID
(Hydrocortisone) (Fludrocortisone)
↓ ↓
Replace Cortisol Replace Aldosterone
Suppress ACTH Maintain BP/Na
Medical Therapy
- Hydrocortisone: Short-acting steroid. Mimics diurnal rhythm.
- Dose: 10-15 mg/m2/day in children.
- Goal: Normalise 17-OHP and Androgens (Growth velocity is best monitor).
- Fludrocortisone: Aldosterone replacement.
- Dose: 50-200 micrograms daily.
- Monitor: BP and Plasma Renin Activity.
- Salt Supplements: Infants often need 1-2g NaCl daily in milk until weaning.
Sick Day Rules (MANDATORY)
- The body normally surges cortisol during stress. CAH kids cannot.
- Education: Parents must carry IM Hydrocortisone emergency kit.
- Moderate Illness (Fever): DOUBLE oral dose.
- Severe Illness (Vomiting): IM HYDROCORTISONE immediately and attend ER.
- Adrenal Crisis: Life-threatening.
- Growth Failure: From overtreatment (Cushingoid) or undertreatment (premature fusion).
- TARTs (Testicular Adrenal Rest Tumours): Benign ectopic adrenal tissue in testes in males. Causes infertility.
- Psychosocial: Gender identity issues.
- Fertility: Reduced in females (anovulation due to antigens) and males (TARTs).
- Height: Final height often 1-2 SD below genetic potential.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| CAH Guideline | Endocrine Society (2018) | Standard of care for diagnosis, monitoring, and sick day rules. |
| DSD Management | ESPE / LWPES | Multidisciplinary team approach for ambiguous genitalia. |
Landmark Evidence
1. Newborn Screening
- Studies confirm screening for 17-OHP prevents salt-wasting death in males. (Not universal in UK, but standard in US/NZ).
What is CAH?
It is a genetic condition where the adrenal glands (hats on the kidneys) have a "factory fault". They are missing the machine (enzyme) that makes Cortisol (stress hormone) and Aldosterone (salt hormone). Because the factory can't make these, the raw materials pile up and overflow into the only open production line: Testosterone (male hormone).
What does the treatment do?
We give back the missing hormones (Hydrocortisone and Fludrocortisone). This keeps the baby safe (stops salt loss) and tells the factory "We have enough cortisol now", so it stops pumping out excess testosterone.
What are "Sick Day Rules"?
Normally when you get sick, your body makes extra cortisol to fight the stress. Your child can't do this. So when they have a fever, you must generally double their tablets. If they vomit and can't keep tablets down, they need an injection immediately, or they can become dangerously ill.
Primary Sources
- Speiser PW, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018.
- Auchus RJ. The classic and nonclassic congenital adrenal hyperplasias. Endocr Rev. 2017.
Common Exam Questions
- Diagnosis: "Male infant, 2 weeks old, shock + High K?"
- Answer: CAH (Salt wasting).
- Biochemistry: "Diagnostic marker?"
- Answer: 17-Hydroxyprogesterone (17-OHP).
- Genetics: "Inheritance pattern?"
- Answer: Autosomal Recessive.
- Management: "Vomiting CAH child?"
- Answer: IM Hydrocortisone + Hospital.
Viva Points
- 11-Beta-Hydroxylase Deficiency: The second most common type. Causes Virilisation AND Hypertension (because Deoxycorticosterone accumulates and acts like Aldosterone).
- Ambiguous Genitalia: Never guess the sex. Say "I would explain to the parents that the genitals are not clearly male or female yet and tests are needed."
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.