[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Congenital adrenal hyperplasia due to 21-hydroxylase deficiency [Conditions](https://durgical.com/en/conditions/) · [Metabolism (biochemistry)](https://durgical.com/en/conditions/) # Congenital adrenal hyperplasia due to 21-hydroxylase deficiency An inherited disease in which the adrenal gland makes too little cortisol and aldosterone and too much androgen; it can cause severe newborn crises. Updated 2026-11-01 ## Structures involved Tap one to see what it is and open it in 3D. - [Right adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland-abdomen/) - [Left adrenal gland](https://durgical.com/en/anatomy/suprarenal-gland/) - [Kidneys](https://durgical.com/en/anatomy/kidney/) - [Clitoris](https://durgical.com/en/anatomy/clitoris/) - [Labia majora](https://durgical.com/en/anatomy/labium-majus-of-vulva/) - [Ovaries](https://durgical.com/en/anatomy/ovary/) ## In biochemistry - [Adrenal cortisol synthesis: Step 4 · 21-Hydroxylase (CYP21A2)](https://durgical.com/en/biochemistry/pathways/adrenal-cortisol-synthesis/#paso-4) - [Adrenal enzymes and congenital adrenal hyperplasia](https://durgical.com/en/biochemistry/topics/adrenal-enzymes-and-congenital-adrenal-hyperplasia/) - [21-Hydroxylase (CYP21A2)](https://durgical.com/en/biochemistry/enzymes/21-hydroxylase/) - [Cortisol](https://durgical.com/en/biochemistry/molecules/cortisol/) - [Aldosterone](https://durgical.com/en/biochemistry/molecules/aldosterone/) - [17-Hydroxyprogesterone (17-OHP)](https://durgical.com/en/biochemistry/molecules/17-hydroxyprogesterone/) ## In embryology - [Adrenal gland: cortex from mesoderm, medulla from neural crest](https://durgical.com/en/embryology/adrenal-gland-cortex-from-mesoderm-medulla-from-neural-crest/) - [Androgens, diethylstilbestrol and other hormones](https://durgical.com/en/embryology/androgens-diethylstilbestrol-and-other-hormones/) - [Sex determination: SRY, anti-Müllerian hormone and testosterone](https://durgical.com/en/embryology/sex-determination-sry-anti-mullerian-hormone-and-testosterone/) - [External genitalia and their male–female homologues](https://durgical.com/en/embryology/external-genitalia-and-their-male-female-homologues/) - [Differences of sex development: CAH, AIS and 5α-reductase](https://durgical.com/en/embryology/differences-of-sex-development-cah-ais-and-5-reductase/) ## In the clinical exam - [Cushing syndrome and adrenal insufficiency: the signs](https://durgical.com/en/clinical-exam/cushing-syndrome-and-adrenal-insufficiency-the-signs/) ## In physiology - [The adrenal cortex: zones, hormones and androgens](https://durgical.com/en/physiology/the-adrenal-cortex-zones-hormones-and-androgens/) - [Puberty](https://durgical.com/en/physiology/puberty/) - [Sex determination and differentiation](https://durgical.com/en/physiology/sex-determination-and-differentiation/) ## Why it happens - [Hyperplasia: physiologic and pathologic](https://durgical.com/en/general-pathology/hyperplasia-physiologic-and-pathologic/) ## What it is An autosomal recessive disorder from CYP21A2 variants that lowers cortisol (and often aldosterone) and diverts precursors into androgens. ## Who gets it The classic form affects about 1 in 15,000 newborns and the non-classic form about 1 in 1,000 people; it causes about 95 % of congenital adrenal hyperplasia. Frequency varies between populations; no Colombian figures are cited here. ## Causes - Variants in both copies of CYP21A2 (chromosome 6p21.3) - Recombination with the neighbouring pseudogene CYP21A1P (deletions and gene conversions) - Autosomal recessive inheritance ## Risk factors - Carrier parents - An affected sibling (25 % risk in each pregnancy) - Consanguinity ## Pathophysiology 21-Hydroxylase turns 17-hydroxyprogesterone into 11-deoxycortisol and progesterone into 11-deoxycorticosterone. Without it cortisol falls, the pituitary releases more ACTH and the cortex enlarges. The piled-up 17-hydroxyprogesterone is diverted by 17,20-lyase into androstenedione and testosterone, which virilise the external genitalia of a female fetus (uterus and ovaries are normal). In the salt-wasting form aldosterone is also missing: the [kidney](https://durgical.com/en/anatomy/kidney/) loses sodium and keeps potassium, and a crisis with dehydration and shock appears around the second week of life. ## Classification - Classic salt-wasting (the most severe) - Classic simple virilising (enough aldosterone) - Non-classic or late-onset (residual enzyme activity) ## Symptoms and signs - Ambiguous genitalia in newborn girls (clitoromegaly, fused labia) - Vomiting, poor feeding and dehydration in the first weeks (salt-wasting) - Pubic hair and fast growth in childhood, with advanced bone age - Short final height - In the non-classic form: hirsutism, acne and irregular cycles in adolescent girls and women ## Red flags - A newborn with vomiting, low sodium, high potassium or hypotension - Hypoglycaemia in the newborn - Ambiguous genitalia: a medical emergency before sex is assigned ## Diagnosis **Clinical** Suspected from ambiguous genitalia, a salt-wasting crisis in a boy with normal genitalia, or early pubarche; newborn screening finds many cases before symptoms. **Tests** Very high 17-hydroxyprogesterone (heel-prick screening; ACTH stimulation test in the non-classic form); low sodium and high potassium; high renin; low cortisol; high androstenedione; karyotype; CYP21A2 genetic testing. **Imaging** Pelvic ultrasound to confirm the uterus and [ovaries](https://durgical.com/en/anatomy/ovary/); hand X-ray for bone age; ultrasound may show enlarged adrenals. ## Treatment **Medical** Glucocorticoid replacement (hydrocortisone in childhood) and mineralocorticoid replacement with salt supplements in salt-wasting infants **Acute** In adrenal crisis: intravenous fluids with glucose and intravenous hydrocortisone **Surgical** Genital surgery in selected cases, decided by a multidisciplinary team with the family **Follow-up** Follow-up of growth, bone age, 17-hydroxyprogesterone and androstenedione; education on stress dosing during illness ## Complications - Adrenal crisis and newborn death if missed - Short stature - Infertility; testicular adrenal rest tumours - Iatrogenic Cushing syndrome from overtreatment ## Prognosis With early diagnosis and lifelong treatment, life expectancy is near normal. ## Prevention - Newborn screening with 17-hydroxyprogesterone - Genetic counselling for families with a case ## Test yourself Think of the answer, then tap the question to see it. ## Which gene is altered in 21-hydroxylase deficiency? CYP21A2, on chromosome 6, next to a pseudogene it recombines with. ## Why are affected girls born with ambiguous genitalia but a normal uterus? Adrenal androgens virilise the external genitalia; the internal female organs form normally because there are no testes or anti-Müllerian hormone. ## Which electrolyte changes does the salt-wasting form cause? Low sodium and high potassium from lack of aldosterone, with high renin. ## Which marker is measured in newborn screening? 17-Hydroxyprogesterone. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/) ## Related conditions - [Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-11-hydroxylase-deficiency/) - [Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency](https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-17-hydroxylase-deficiency/) - [Adrenal insufficiency](https://durgical.com/en/conditions/adrenal-insufficiency/) - [Polycystic ovary syndrome](https://durgical.com/en/conditions/polycystic-ovary-syndrome/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [21-hydroxylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/21-hydroxylase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [CYP21A2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/cyp21a2/) (MedlinePlus, US National Library of Medicine, 2026); [Congenital adrenal hyperplasia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000411.htm) (MedlinePlus, US National Library of Medicine, 2026). [← All conditions](https://durgical.com/en/conditions/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/congenital-adrenal-hyperplasia-due-to-21-hydroxylase-deficiency/