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.
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What this article covers
- Overview
Definition: 11-beta-hydroxylase deficiency is an autosomal recessive defect in the CYP11B1 enzyme that blocks conversion of 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone…
- Epidemiology
Second most common CAH enzyme defect: 11-beta-hydroxylase deficiency accounts for a small minority of CAH cases, well behind 21-hydroxylase deficiency in frequency.
- Risk factors
Two carrier parents: Inheriting a nonfunctional CYP11B1 allele from each parent is required for the disease to manifest.
- Pathophysiology
Blocked conversion step: 11-beta-hydroxylase normally converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone (the immediate precursor of aldosterone); loss of this enzyme…
- Clinical features
Diagnostic anchor: The defining feature is virilization from androgen excess together with hypertension and hypokalemia, in a patient with elevated 11-deoxycortisol and 11-deoxycorticosterone and low cortisol.
- Differential diagnosis
21-hydroxylase deficiency: Also virilizes a genetic female, but causes hypotension, hyponatremia, and hyperkalemia from aldosterone deficiency rather than the hypertension and hypokalemia of 11-beta-hydroxylase deficiency.
- Diagnosis
Clinching diagnostic basis: Elevated serum 11-deoxycortisol and 11-deoxycorticosterone, together with low cortisol, in a patient with virilization, hypertension, and hypokalemia, establishes…
- Management
First, confirm the diagnosis and assess severity of hypertension and low serum potassium: Obtain blood pressure, a basic metabolic panel, and the diagnostic hormone panel before starting therapy…
- Complications
Sustained hypertension and its sequelae: Undertreated disease can cause chronic hypertension with long-term cardiovascular and renal consequences if glucocorticoid suppression of ACTH is inadequate.
- Prognosis
Good with adherent therapy: Consistent glucocorticoid replacement corrects ACTH-driven precursor overproduction and typically controls blood pressure, potassium, and androgen excess together.
- Prevention
Early diagnosis in a virilized newborn: Checking 11-deoxycortisol and 11-deoxycorticosterone, not only 17-hydroxyprogesterone, in a virilized infant with hypertension prevents a missed or delayed diagnosis.
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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.
- 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.
- 17-alpha-hydroxylase deficiency
17-alpha-hydroxylase deficiency is a rare autosomal recessive form of congenital adrenal hyperplasia in which CYP17A1 loss blocks cortisol and sex-steroid synthesis while shunting precursors into mineralocorticoid excess, producing hypertension, hypokalemia, and sexual infantilism. First-line treatment is daily glucocorticoid replacement (hydrocortisone) to suppress ACTH-driven deoxycorticosterone and corticosterone overproduction, combined with sex-hormone replacement to induce puberty.
- Adrenal crisis
Adrenal crisis is life-threatening acute glucocorticoid deficiency, most often precipitated by infection or another physiologic stress in a patient with known or unrecognized adrenal insufficiency, presenting with dehydration, hypotension, or shock out of proportion to the concurrent illness. Treatment is immediate intravenous hydrocortisone 100 mg followed by 50 mg every 6 hours plus isotonic saline with dextrose, without waiting for confirmatory labs.
- Cushing syndrome
Cushing syndrome is the clinical state of chronic glucocorticoid excess from any cause, most often exogenous glucocorticoid use, diagnosed by demonstrating loss of normal cortisol suppression or diurnal rhythm with at least two of three screening tests. Treatment targets the underlying source: withdrawal or tapering of exogenous steroid, transsphenoidal surgery for a pituitary cause, or adrenalectomy for an adrenal or ectopic tumor, with steroidogenesis inhibitors reserved for persistent or unresectable disease.