21-hydroxylase deficiency
21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia, an autosomal recessive block in cortisol and aldosterone synthesis that shunts precursors into androgen production, causing salt wasting, hypotension, and virilization in the classic form. First-line treatment is lifelong glucocorticoid replacement, with fludrocortisone and sodium chloride added when salt wasting is present.
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What this article covers
- Overview
Definition: 21-hydroxylase deficiency is an autosomal recessive defect in the CYP21A2 enzyme that blocks conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to…
- Epidemiology
Most common CAH enzyme defect: 21-hydroxylase deficiency causes the large majority of congenital adrenal hyperplasia, making it the enzyme defect a clinician is most likely to encounter.
- Risk factors
Two carrier parents: Inheriting a nonfunctional CYP21A2 allele from each parent is required for classic or nonclassic 21-hydroxylase deficiency to manifest.
- Pathophysiology
Blocked conversion step: 21-hydroxylase normally converts 17-hydroxyprogesterone to 11-deoxycortisol (the immediate cortisol precursor) and progesterone to 11-deoxycorticosterone (the aldosterone…
- Clinical features
Diagnostic anchor: The defining feature is virilization from androgen excess, with or without a salt-wasting crisis, in a patient with sharply elevated 17-hydroxyprogesterone and low cortisol.
- Differential diagnosis
11-beta-hydroxylase deficiency: Also virilizes a genetic female, but causes hypertension and hypokalemia from deoxycorticosterone accumulation rather than the hypotension and hyperkalemia of salt-wasting 21-hydroxylase deficiency.
- Diagnosis
Clinching diagnostic basis: A markedly elevated serum 17-hydroxyprogesterone, together with low cortisol and the corresponding clinical and electrolyte pattern, establishes 21-hydroxylase deficiency…
- Management
First, treat any salt-wasting crisis immediately: Give isotonic fluid resuscitation for dehydration and hypotension, correct hypoglycemia, and give hydrocortisone 100 mg IV bolus, then 50 mg IV every…
- Complications
Adrenal crisis: Missed or inadequate stress dosing during illness can precipitate life-threatening hypotension, hyperkalemia, and hypoglycemia, particularly in infants with salt-wasting disease.
- Prognosis
Good with adherent therapy: With consistent glucocorticoid and, when needed, mineralocorticoid replacement, most patients achieve normal growth, pubertal development, and fertility, though final…
- Prevention
Universal newborn screening: Screening every newborn for elevated 17-hydroxyprogesterone identifies classic disease before a salt-wasting crisis develops, typically within the first 1 to 2 weeks of life.
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Related articles
- Congenital adrenal hyperplasia
Congenital adrenal hyperplasia is a family of autosomal recessive enzyme defects in adrenal steroidogenesis that impair cortisol synthesis, drive ACTH-mediated adrenal hyperplasia, and shunt steroid precursors toward androgen or mineralocorticoid excess depending on which enzyme is deficient. First-line treatment is lifelong glucocorticoid replacement, with mineralocorticoid replacement added when salt wasting is present.
- 11-beta-hydroxylase deficiency
11-beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, an autosomal recessive block in cortisol synthesis that shunts precursors into deoxycorticosterone and androgens, causing hypertension, hypokalemia, and virilization rather than the salt wasting of 21-hydroxylase deficiency. First-line treatment is lifelong glucocorticoid replacement to suppress ACTH and precursor overproduction.
- Adrenal crisis
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- 17-alpha-hydroxylase deficiency
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