Congenital adrenal hyperplasia

The single fact that organises everything in congenital adrenal hyperplasia is the enzyme block. Stop cortisol production and the pituitary loses its negative feedback, so ACTH climbs and the adrenal cortex hyperplasia. The precursors that cannot pass the block pile up behind it and spill into the androgen pathway. That is why one genetic disease shows up as a salt-losing crisis, an endocrine emergency, and a disorder of sex development all at once. ^{[2] [3]}

This page covers the recognition and management of congenital adrenal hyperplasia: the clinical forms, steroidogenesis block, salt-wasting crisis, ambiguous genitalia, the 17-hydroxyprogesterone newborn screen and its pitfalls, the confirmatory work-up, acute resuscitation, lifelong glucocorticoid and mineralocorticoid replacement, and family counselling. It links to the dedicated leaves for disorders of sex development and adrenal insufficiency rather than repeating their full pathways. ^[1]

Overview & Definition

Congenital adrenal hyperplasia is a family of autosomal recessive enzyme defects of adrenal steroidogenesis. More than nine in ten cases are 21-hydroxylase deficiency caused by mutations in CYP21A2, and the rest are rarer defects such as 11β-hydroxylase, 3β-hydroxysteroid dehydrogenase, 17α-hydroxylase and the StAR cholesterol-transport defect. The unifying mechanism is partial or complete loss of an enzyme that the adrenal cortex needs to make cortisol, with a knock-on rise in ACTH and a build-up of upstream precursors. ^[2]

The clinically useful distinction is between classic and non-classic disease. Classic 21-hydroxylase deficiency has little or no enzyme activity and presents in the newborn period — most often with salt-wasting, sometimes with virilisation alone. Non-classic disease retains enough activity to escape the newborn period and declares itself later with signs of androgen excess. The distinction matters at the bedside because the classic salt-wasting form is a time-critical neonatal emergency. ^{[1] [7]}

References11ShowHide

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2. [2]White PC; Speiser PW Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev, 2000.PMID 10857554
3. [3]Merke DP; Bornstein SR Congenital adrenal hyperplasia. Lancet, 2005.PMID 15964450
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8. [8]Sarafoglou K; Banks K; Kyllo C; et al Cases of congenital adrenal hyperplasia missed by newborn screening in Minnesota. JAMA, 2012.PMID 22692165
9. [9]New MI; Abraham M; Gonzalez B; et al Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Proc Natl Acad Sci U S A, 2013.PMID 23359698
10. [10]Houk CP; Hughes IA; Ahmed SF; et al Summary of consensus statement on intersex disorders and their management. Pediatrics, 2006.PMID 16882833
11. [11]Engström K; Zetterström RH; Wedell A; et al Neonatal Screening for CAH in Sweden—Results of Implementing Second-Tier Testing. Int J Neonatal Screen, 2026.PMID 42201221